Official reprint from UpToDate®

www.uptodate.com ©2018 UpToDate, Inc. and/or its affiliates. All Rights Reser
ved.

Diagnostic approach to children and adolescents with short stature

Author: Alan D Rogol, MD, PhD

Section Editor: Mitchell E Geffner, MD
Deputy Editor: Alison G Hoppin, MD

All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2018. | This topic last updated: Mar 02, 2018.

INTRODUCTION — Short stature is defined as a height that is2 standard deviations (SD) or more below the mean height for individuals of the same sex and chr
onologic
age in a given population. This translates to a height that is below the 2.3rd percentile.

The most common causes of short stature beyond the first year or two of life are familial (genetic) short stature and constitutional short stature (also known as
constitutional delay of growth and puberty), which are normal nonpathologic variants of growth. These growth patterns often can be distinguished fr om one another, but
some children have features of both (see "Causes of short stature", section on 'Normal variants of growth'). The goal of the evaluation of a child with short stature is to
identify the subset of children with pathologic causes, such as Turner syndrome, inflammatory bowel disease or other underlying systemic disease, or hormonal
abnormality. The evaluation also assessesthe severity of the short stature and likely growth trajectory, to facilitate decisions about intervention, if appropriate. Some
components of the evaluation can reasonably be performed in the primary care setting, including initial interpretation of the growth chart and growth potential (based on
measured heights of the child's parents), calculation of height velocity (HV), initial laboratory screening for an underlying systemic or endocrine disease, if suspected
based on symptoms. If HV is slow, then bone age determination should be per formed if expert interpretation is available. Other components of the evaluation, including
review of the bone age results and the detailed evaluation for causes of short stature, are typically performed by a pediatric endocrinologist, if available.

Referral patterns reveal substantial sex differences in the evaluation and treatment of short stature [1-4]. Boys are referred for evaluation more often, at younger ages and
for less severe height deficits as compared with girls. As an example, in one etrospective
r review of 288 children referred to a single center for assessment of short
stature, the male:female ratio was 1.9:1 [1]. At the time of referral, the height deficitwas significantly greater for girls than boys (median height Z-score, -2.4 versus -1.9),
and organic disease was more common among girls (40 versus 15 percent). Similarly, studies of growth hormone registries have shown preferential treatment of boys
compared with girls with an approximate ratio of 2:1 [2,3].

This apparent gender bias may be due to under-appreciation of growth problems in girls, leading to fewer evaluations of girls for short stature. Alternatively, it may be due
to increased societal pressure for tall stature in boys, leading to increased referral and growth hormone treatment of boys without organic causes of short stature. These
findings emphasize the need for accurate growth monitoring during the health care maintenance of all children to ensure appropriate referral and treatment.

This topic will review the diagnostic approach to children with short stature, beginning with a brief review of normal growth and development. The causes of short stature
are discussed separately. (See "Causes of short stature".)

NORMAL GROWTH — Serial measurements of growth are an important parameter in monitoring the health of children. In general, a normal pattern of growth suggests
good health, while growth that is slower than normal raises the possibility of an underlying subacute or chr
onic illness, including an endocrinologic cause of gr
owth failure.

Statural growth is a continuous but not linear process. There are three phases of postnatal growth (infantile, childhood, and pubertal), each of which has a distinctive
pattern [5]. The phases are similar for boys and girls, but the timing and pace of growth differ, particularly during puberty.

● Intrauterine – Size at birth is determined more by maternal nutrition and intrauterine and placental factors than by genetic makeup. Not all the genes that affect
growth may be expressed at birth. As a result, the correlation coefficient between birth length and adult height is only 0.25 6].
[

● Infancy – During the first two years of life (infantile phase), linear growth initially is very rapid and gradually decelerates. Overall growth during this period is about 30
to 35 cm. The length (and weight) of premature infants must be corrected for gestational age, at least for the first ear. y However, growth is often accelerated during
the second half of the first year in otherwise healthy children born early.

An infant's height curve often crosses percentile lines during the first 24 months of lif
e as the growth moves away from the influences of the intrauterine environment
and toward the child's genetic potential. As examples, infants born small because of placental or uterine constr
aint may move upwards across percentile curves
("channeling up"), whereas infants born large because of maternal-fetal overnutrition may cross downward across percentile curves ("channeling down"). After this
adjustment period, the correlation between length at two years and adult height is 0.80 [6].

● Childhood – The childhood phase is char acterized by linear growth at a relatively constant velocity, with some slowing in later childhood. Most childr
en grow at the
following rates (representing the 10th to 90th percentiles):

• Age two to four years: 5.5 to 9 cm/year (2.2 to 3.5 inches/year)

• Age four to six years: 5 to 8.5 cm/year (2 to 3.3 inches/year)

• Age six years to puberty:

- 4 to 6 cm/year for boys (1.6 to 2.4 inches/year)

- 4.5 to 6.5 cm/year for girls (1.8 to 2.6 inches/year)

● Adolescence – The pubertal phase is characterized by a growth spurt of 8 to 14 cm per year due to the synergistic effects of increasing gonadal steroids and growth
hormone [7]. In girls, the pubertal growth spurt typically starts around age 10, but may start as early as age 8 for early maturing girls. In bo
ys, the pubertal growth
spurt typically starts around age 12, but may start as early as age 10 in early maturing boys [8].

The "rule of fives" incorporates these typical phases of growth and provides an estimate for normal height and height elocity
v in a given age group, as shown in the table
(figure 1). Actual height and growth rate in a healthy child can vary substantially around these approximations.

EVALUATION OF GROWTH — Evaluation of a child suspected of having short stature is guided by answering the following questions. Although the causes and clinical
presentation of short stature vary by age group, the same questions are relevant for children of any age:

● How short is the child?

● Is the child's height velocity (HV) impaired?

● What is the child's likely adult height?

The answers to these questions guide a focused history and physical examination,and in some cases laboratory evaluation, to determine the cause and appropriate
management of the child with short stature (algorithm 1).

Is the child short? — Accurate measurement of length or height is essential; inaccur ate measurements or aberrant plotting is one of the more common causes of apparent
growth failure. Length is measured lying down and should be used for infants and childr en up to 24 months of age (figure 2A-B); height is measured standing and should
be used for children two years and older (if possible) (figure 3 and figure 4A-B). The results should be plotted on the growth chart that is appropriate for the child's age and
gender. Weight should also be measured to provide additional information about the child' s nutritional status. (See"Measurement of growth in children".)

Percentiles and Z-scores can be calculated using a calculator for recumbent length (calculator 1), or standing height for boys (calculator 2) or for girls (calculator 3). For
the purposes of an endocrine evaluation, short stature is defined as a length or height more than 2 standard deviations (SD) below the mean (ie, a Z-scor e <-2), which
corresponds to a height that is <2.3rd percentile.

● Height above the 2.3rd percentile (>-2 SD) – These children generally do not require further specific evaluation unless there are additional reasons for concern, such as
progressively decreasing height percentiles (implying growth failure), dysmorphic features, evidence of underlying systemic disease, or if the y are growing well below
their genetic potential (eg, they are children of very tall parents).

● Height below the 2.3rd percentile (≤-2 SD) – These children have short stature and should undergo a more detailed evaluation, starting with evaluation of growth rate,
as outlined in the following sections. The first steps of this valuation
e usually can be performed in the primary care setting. Early referral to a specialist is appropriate,
if the growth rate is very slow.

● Height less than the 1st percentile (≤-2.25 SD) – These children have extreme short stature and usually should be referred to an appropriate subspecialist for a
detailed evaluation, where available. The first steps in the evaluation will be similar, but a higher index of suspicion for pathologic causes of gr
owth failure is
appropriate.

Is the child's height velocity impaired? — Determination of the child's growth rate, or HV, is an essential component of the evaluation for short stature and can be
considered a "vital sign" (algorithm 1). This requires serial measurements of height, which should be measured along with weight at each well-child visit. Serial
measurements help to determine whether the child's HV is within normal range and whether it progressively deviates from its previous growth channel (or percentile
curve). The HV should be calculated (incm/year) using accurate measurements of height and an interval between measurements of at least six months.

For children two years and older, growth failure is likely if:

● The height-for-age curve has deviated downwards across two major height percentile curves (eg, from above the 25th percentile to below the 10th percentile).

● Or, if the child is growing slower than the following rates:

• Age two to four years: HV less than 5.5cm/year (<2.2 inches/year)

• Age four to six years: HV less than 5cm/year (<2 inches/year)

• Age six years to puberty:

- HV less than 4 cm/year for boys (<1.6 inches/year)

- HV less than 4.5 cm/year for girls (<1.8 inches/year)

Short children with HV above these cut points usually have a nonpathologic cause of short stature, such as familial short stature or constitutional delay of growth. For
these children, a basic evaluation for short stature usually is sufficient, consisting of a focused hist
ory, physical examination, adult height prediction, and bone age
determination, as outlined in the following sections9].[ (See 'Prediction of adult height'below and 'Bone age determination' below.)  

Short children with HV below these cut points are more likely to have a pathologic cause of short stature and warrant additional attention. In addition ot the basic
evaluation outlined above, laboratory screening for pathologic causes of growth failure is warranted. The clinician should be particularly alert for subtle symptoms of
underlying systemic disease (eg, Crohn disease) and for evidence of Turner syndrome in girls [9]. The detailed evaluation may be most appropriately performed by a
pediatric endocrinologist, if available. (See 'Laboratory and imaging studies'below.)

Short children with HV substantially belowthese cut points are most likely to have a pathologic cause of short stature and should undergo a detailed evaluation for
pathologic causes of growth failure by a pediatric subspecialist, if available.

Alternatively, for a more precise assessment, the child's HV can be plotted on an HV chart (figure 5A-B) to determine the HV percentile (or SD [Z-score]) for the child's age
and gender (note that this is different from the height-for-age percentile). In general, HV between the 10th and 25th percentile should raise concern for possible growth
failure, and an HV below the 10th percentile warrants a thorough evaluation for growth failure.

Prediction of adult height — Adult height is determined by a combination of genetic potential and many other factors that influence somatic growth and biologic
maturation. No method accurately predicts adult height, and there is wide variation in predicted adult height among the different methods. However, an estimate of adult
height can be developed using information about heights in the biologic family, combined with information about the child's own growth and level of skeletal development.
The results help to guide decisions about evaluation and treatment, and also provide some information about the possible causes of shor t stature in a particular patient.

Is the child’s growth within the range for the family? — The next step is to determine the height range expected for the child's biologic family and compare it with the
child's growth trajectory. In most populations, a predicted adult height that is <63 inches (160 cm) for men and <59 inches (150 cm) for women is consider ed short stature,
corresponding to more than 2 SD below the mean (<2.3rd percentile) for adults of the same population and gender.

● Midparental height – An estimate of a child's genetic height potential can be obtained by calculation of the midparental height, which is based upon the heights of
both parents and adjusted for the sex of ht e child (algorithm 1). This estimate is also known as the "tar
get height". Whenever possible, the parents' heights should be
directly measured rather than self-reported. The calculation can be performed using a calculator (calculator 4) or the following equation:

• For girls, 13 cm (or 5 inches) is subtracted from the father's height and averaged with the mother's height.

• For boys, 13 cm (or 5 inches) is added ot the mother's height and averaged with the father's height.

• For both girls and boys, 8.5 cm (3.3 inches) on either side of this calculated value (target height) represents the 3rd to 97th percentiles for anticipated adult
height [10].

In this calculation, the 13 cm (or 5 inches) epresent

r the average difference in the average height of adult men and women. Thus, the child gr
ows, on average, to
the midparental height percentile.

● Projected height – The projected height for a child older than two years is determined by extrapolating the child's growth along the current channel to the 18- to 20-
year mark (figure 6). If the child's bone age is delayed or advanced, then the projected height should be plotted based on the bone ageather
r than the chronologic age.
(See 'Bone age determination' below.)
The child's projected height is then compared with the range calculated from the midparental (target) height.

● If the child's projected height is within 8.5 cm (2 SD) of the midpar

ental height, then the child's height is within the expected ar nge for the family. This child probably
has familial short stature, which is considered a variant of normal growth. (See "Causes of short stature", section on 'Familial short stature'.)

● If the projected height is more than 8.5 cm (2 SD) below the midparental height, then the child can be consider
ed abnormally short for his or her family.

Is there evidence of delayed or accelerated growth? — Most children with severe short stature (height <-2.25 SD) or growth failure should undergo a radiographic
determination of bone age. This helps ot determine whether the child's growth is delayed or accelerated compared with his or her chronological age.

Bone age determination — Bone age (also known as skeletal age) is typically determined from a radiograph of the left hand and wrist, and equires
r expert
interpretation. The methods used most commonly for determining skeletal age are the Greulich and Pyle Atlas [11] and the Tanner-Whitehouse (TW3) method [12]. In
general, TW3 is considered to be more accurate, based on studies in predominantly white European populations [13]. However, bone ages obtained from these methods
are less generalizable to children of non-white ethnicities; African American children tend to have advanced bone age, and Southeast Asian childr
en tend to have delayed
bone age, compared with their white peers[14,15].

The bone age determination informs estimates of the child'

s growth potential and likely adult height, as follows:

● Delayed or advanced bone age is defined as a bone age that is 2 SD or mor e below or above the mean, respectively. This is approximately 20 percent below or above
the chronological age. This translates to a difference between bone age and chronological age of approximately 12 months between 2 and 4 e y ars of chronological
age, 18 months between 4 and 12 years, and 24 months after age 12 fi( gure 7A-B). If the bone age is delayed or advanced near or beyond these parameters, then the
projected height should be recalculated based on the bone age ather
r than the chronologic age. This will provide a more accurate assessment of projected height. As
an example, if an eight-year-old boy is 117 cm tall and has a bone age of 6.5 eyars, this corresponds to the 3rd percentile for chronological age, but to the 35th
percentile for skeletal age, suggesting that the child may have constitutional delay of growth.  

● The bone age can be used o t predict the child's adult height. The technique developed by Bayley-Pinneau (BP) is most commonly used for childr en approximately six
years and older [16]. This technique employs a table to translate the child's bone age and chronological age to a decimal fraction of adult height (eg, 0.75). T
o predict
adult height, the present height is dividedby the fraction of adult height.

Other methods use different algorithms to predict adult height from height measurements and bone age data, and include the a Tnner-Whitehouse 3 (TW3), Roche-
Wainer-Thissen (RWT), and Khamis-Roche(KR) methods. RWT and KR incorporate midparental height in addition to bone age, and TW3 uses a skeletal maturity
score. Comparison of these methods er veals a wide range of adult height predictions. Overall, the TW3 method (or the previous version, TW2) either under-predicts or
over-predicts adult height in about 30 percent of individuals [17,18], while the BP and RWT methods tend to over-predict adult height in boys [19]. The BP method is
most likely to identify a short child as a candidate for growth hormone therapy [20]. Methods that incorporate bone age are generally more accurate in predicting adult
height than the simple midparental height method. However, there is a wide variation in height prediction, and the same method may yield significantly different adult
height predictions at different ages [19].

The results of the bone age determinationalso provide important information about possible causes of the shor
t stature (algorithm 1):

● A significantly delayed bone age is consistent with constitutional dela y of growth and puberty (CDGP), which is considered a variant of normal growth. However,
significantly delayed bone age is also seen in many types of pathologic gr owth failure, including nutritional deficiency,underlying systemic disease (such as
inflammatory bowel disease), and growth hormone deficiency. The HV helps to distinguish between these categories: childr en with CDGP tend to have normal or low-
normal HV until they reach bone age of 11years in girls, or 13 years in boys. By contrast, children with underlying systemic or endocrine disease tendot have
progressive decreases in HV. Children with significantly delayed bone age should undergo a focused history and physical examination o t evaluate for symptoms and
signs of systemic or endocrine disease (see'Additional evaluation for causes of short stature' below). Their growth should also be carefully monitored.

● A normal bone age is consistent with several diagnostic possibilities: in a child with shor
t parents, a normal bone age supports the diagnosis of familial short stature.
However, a normal bone age is also seen in younger girls with Turner syndrome. Moreover, bone age may be only mildly delayed in early or mild forms of some of the
systemic diseases that cause growth failure. Therefore, a bone age that is within normal limits suggests that underlying genetic or systemic disease is unlik
ely, but
not impossible.

● Advanced bone age is occasionally seen in older childr en and adolescents with short stature, especially precocious puberty and hyperthyroidism. These children
usually experienced accelerated early growth but are at risk for early epiphysial closure, resulting in short stature as an adult, if not properly diagnosed and treated.
(See "Causes of short stature", section on 'Sexual precocity'.)

ADDITIONAL EVALUATION FOR CAUSES OF SHORT STATURE — In addition to the evaluation of growth outlined above, a focused history and physical examination
contribute information that helps ot categorize the cause of short stature (table 1 and algorithm 1). The key information is organized here according to the diagnostic
category of the short stature. Further details about each cause of short stature are given in the linked topic review. (See "Causes of short stature".)

Are there features that suggest that this si a normal variant of short stature? — The two most common causes of short stature are familial (genetic) short stature and
constitutional delay of growth and puberty (CDGP, also termed constitutional short stature for prepubertal children). These growth patterns often can be distinguished
from one another, but some children have features of both (table 2). Unless there are signs or symptoms of underlying disease, children with these growth patterns usually
require only a basic evaluation including a focused history, physical examination, and bone age determination. (See'Laboratory and imaging studies'below.)

● In familial short stature, height velocity (HV) and bone age are within the normal range and one or both parents are short. (See "Causes of short stature", section on
'Familial short stature'.)

● In CDGP, the child's growth rate is appropriate for his or her bone age, which is delayed compared with chronological age. If the height is plotted using the bone age
rather than chronological age, the projected height is within the range predicted for the family and often within the normalanger for the population (ie, adult height
that is ≥63 inches [160 cm] for men and ≥59 inches [150 cm] for women). Ther e is often a family history of delayed growth and/or puberty (a parent who was a "late
bloomer"). (See "Causes of short stature", section on 'Constitutional delay of growth and puberty'.)

Are there features suggesting pathologicgrowth failure? — The history, review of systems, and physical examination should include the following elementsot assess for
a variety of pathologic causes of short stature (table 1 and algorithm 1). The findings may influence selection of laboratory tests and/or imaging.

Features suggesting underlying systemic disease  — A variety of systemic diseases are associated with attenuated growth during childhood, usually with delayed bone
age. This is particularly true for inflammatory disease processes (such as Crohn disease or juvenile idiopathic arthritis [JIA]), diseases that cause malabsorption or
malnutrition, or those that increase energy needs (cardiac or immune defects). Therefore, a complete medical history and review of systems is important to the
assessment of short stature.

Key elements of the history include (see "Causes of short stature", section on 'Systemic disorders with secondary effects on growth'):

● Gastrointestinal symptoms, including appetite, abdominal pain, diarrhea, andectal

r bleeding – Suggests the possibility of Cr
ohn disease or celiac disease.

● Pulmonary symptoms, including severe asthma, recurrent infections – Suggests the possibility of cystic fibr
osis or immunodeficiency.
 ● Recurrent infections – Suggests the possibility of immunodeficiency;ecurrent
r otitis media with the need for myringot
omy tubes is associated with Turner syndrome.

● Arthralgia or arthritis – Consistent with inflammatory bowel disease, rheumatic diseases (eg, JIA), or celiac disease.

● Medications – Prolonged or frequent use of glucocorticoids (including inhaled glucocorticoids) may contribute to growth failure (see "Causes of short stature",
section on 'Glucocorticoid therapy'). Use of stimulants for attention deficit disorder (ADD) also has been associated with mild dela
y in growth, although this effect
usually is transient. (See "Causes of short stature", section on 'Systemic disorders with secondary effects on growth' and "Pharmacology of drugs used ot treat
attention deficit hyperactivity disorder in children and adolescents", section on 'General adverse effects'.)

Key elements of the physical examinationinclude:

● Weight loss, poor weight gain, underweight-for-height, and/or delayed puberty – These findings are consistent with many underlying systemic diseases, psy
chosocial
deprivation, or food restriction. By contrast, most endocrine causes of short stature are associated with overweight-for-height.

● Oral ulcers or large anal skin tags – These findings are common in Crohn disease and may be the presenting symptoms.

Features suggesting genetic or endocrine disease  — Endocrine disorders are relatively uncommon causes of short stature but important to diagnose because they
respond to specific treatment. These endocrine disorders are often characterized by delayed bone age. An exception is precocious puberty, in which accelerated early
growth may be accompanied by early epiphyseal maturation and adult short stature.

Key elements of the history relevant to endocrine disease include (see"Causes of short stature", section on 'Endocrine causes of growth failure'):

● Sluggishness, lethargy, cold intolerance, constipation – These symptoms suggest hypothyroidism.

● Developmental delay/learning disabilities – Problems with nonverbal learning skills are common in Turner syndrome. Developmental delay is common in Noonan or
Russell-Silver syndrome, and in pseudohypoparathyroidism. Acquired hypothyroidism is often associated with altered school performance. Many syndromes with
developmental delay also include short stature, such as Down, Prader-Willi, and Bloom syndromes.

● Neuropsychological changes – Symptoms of psychiatric disease occur in over one-half of patients with Cushing syndr
ome of any etiology.

Key elements of the physical examinationinclude:

● Increased weight-for-height – Obesity is nearly universal in Cushing syndrome (with central fat distribution). Increased weight-for-height is also consistent with
hypothyroidism, growth hormone deficiency, or pseudohypoparathyroidism.

● Facial dysmorphism

• Hypertelorism, downward eye slant, low-set ears – Noonan syndrome

• Prominent forehead, triangular face, downturned corners of the mouth – Russell-Sil

ver syndrome

• Midface hypoplasia, frontal bossing – Achondroplasia

• Midline defects – Associated with hypothalamic-pituitary hormone deficiencies

● Optic discs – Papilledema suggests a central nervous system mass effect. Optic nerve hypoplasia suggests septo-optic dysplasia, which is associated with pituitar
y
hormone deficiencies. In optic nerve hypoplasia, the optic disc is small and often pale and surr
ounded by a yellowish halo bordered by a ring of pigmentation (double-
ring sign) (picture 1).

● Neck and chest

• Goiter – Hypothyroidism.

• Webbed neck, shield chest (picture 2) – Characteristic findings in Turner syndrome.

• Webbed neck, pectus excavatum – Seen in Noonan syndrome.

• Suprascapular fat pad (buffalo hump) andsupraclavicular fat pads – Suggests Cushing syndr
ome. Mild forms of this fat distribution ar
e seen in simple obesity
(sometimes termed "pseudo-Cushingoid"), but exogenously obese children are often of normal or slightly increased stature.

● Limbs

• Cubitus valgus (increased carrying angle of the arm), genu valgum – Commonly seen in Turner syndrome or Short Stature HOmeoboX (SHOX) mutations

• Madelung deformity of the forearm (focal dysplasia of the distal radial physis, leading to a prominent ulna and wrist pain) p
( icture 3 and image 1) – Commonly
seen in Turner syndrome or SHOX mutations

• Stocky build – Often seen in Turner syndrome or SHOX mutations

• Long limbs compared with trunk – Spondyloepiphysial dysplasia

• Short limbs (especially upper arms) compared with trunk – Achondroplasia

• Trident hands (broad, space between middle fingers) – Achondr

oplasia

● Skin – Atrophied skin, purple-colored striae are characteristic of Cushing syndrome, sometimes with hyperpigmentation.

● Delayed or accelerated puberty, or hypogonadism – Most women with T urner syndrome have absent breast development; some have delayed puberty. Hypothyroidism
tends to cause pubertal delay although, on rare occasion, this disorder may present with precocious puberty. Early puberty is occasionally seen in congenital virilizing
adrenal hyperplasia or Cushing disease. Microphallus or cryptorchidism suggests central hypothalamic-pituitary deficiencies.

● Decreased deep tendon reflexes – Suggests hypothyroidism.

LABORATORY AND IMAGING STUDIES — There is some controversy about the extent of testing that should be per formed for children and adolescents with presumed
idiopathic short stature (ISS). In otherwise healthy children, the yield of testing is extremely low. One study described the clinical evaluation of 235 children who were
referred for short stature and had height <3rd percentile, but normal growth rate and no symptoms [21]. In this group of low-risk short children, nearly 99 percent were
ultimately diagnosed with variants of normal growth (23 percent with familial short stature, 41 percent with constitutional delay of growth, and 36 percent with ISS). The
cost per new diagnosis identified was mor e than $100,000, although most patients did not under go all of the screening tests that have been recommended in consensus
guidelines [9]. Because of the low diagnostic yield and high cost, we suggest per forming laboratory testing only selectively in otherwise asymptomatic children, as outlined
below.
 ● A basic evaluation consisting of a bone age determination is appr opriate for children with short stature, normal growth rate (eg, height velocity [HV] at least 5 cm/year
between four and six years of age, and at least 4cm/year between six years and puberty), and no other symptoms. The bone age determination provides a more
accurate assessment of adult height andclarifies the type of growth defect, as described above (see 'Is there evidence of delayed or accelerated growth?' above).
Screening for celiac disease is also er asonable for children with gastrointestinal symptoms or first-degree relatives with celiac disease.

● Broader testing may be warranted if the child is severely short (eg, height ≤-2.5 standard deviations [SD, 0.6th percentile]), has growth failure (eg, height-for-age curve
crossing two major percentile lines, or HV <5cm/year between four and six years of age, and <4cm/year between six years and puberty), or if the history or physical
examination raised suspicion for a specific systemic, endocrine, or genetic disorder. Decisions regarding the extent of testing should be made in conjunction with a
pediatric subspecialist, but vary with the child's presenting symptoms and the clinical setting. We perform the following battery of tests to screen for several
pathologic causes of short stature (table 1), as outlined in a consensus statement9]: [

• Complete blood count and erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP).

• Electrolytes, creatinine, bicarbonate, calcium, phosphate, alkaline phosphatase, albu

min.

• Celiac serologies (eg, tissue transglutaminase [tTG] immunoglobulin A [IgA] and ot tal IgA) – Several guidelines recommend celiac screening for short stature, as
well as for other indications. This test is elatively
r cost effective and screens for a common disease. Some celiac disease test panels include a measur ement of
total IgA, to exclude the unlikely possibility of a false-negative test in a patient with selective IgA deficiency. (See "Diagnosis of celiac disease in children", section
on 'Whom to test'.)

• Thyroid stimulating hormone (TSH), free thyroxine (T4), insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein 3 (IGFBP-3). IGFBP-3 has
higher sensitivity for predicting the diagnosis of growth hormone deficiency in children <10 years of age as compared with IGF-I.

• Karyotype (in all girls, to rule out Turner syndrome, and in boys with associated genital abnormalities).

• Morning luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in childr

en with signs of sexual precocity ("ultrasensitive" assays should be used for
pediatric patients, and samples should be dr
awn in the early morning for optimal sensitivity). (See"Definition, etiology, and evaluation of precocious puberty".)

Additional testing for specific disorders is appropriate if the history and physical examination suggest a particular diagnosis, such as precocious puberty or an endocrine,
skeletal, or syndromic cause of growth failure, as described above. (See 'Are there features suggesting pathologic growth failure?' above and "Causes of short stature",
section on 'Pathologic causes of growth failure' and "Skeletal dysplasias: Approach to evaluation".)

Patients with reduced HV and low IGF-Iand/or IGFBP-3 and delayed bone age should be evaluated for growth hormone deficiency using provocative tests. (See "Diagnosis
of growth hormone deficiency in children".)

Contrast-enhanced magnetic resonance imaging (MRI) of the brain is appropriate for children with established growth hormone deficiency, or in those with signs or
symptoms suggesting hypothalamic-pituitary dysfunction (eg, hypoglycemia, microphallus, cryptorchidism, septo-optic dysplasia, intracranial tumor, or history of cranial
irradiation).

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and e r gions around the world are provided separately. (See
"Society guideline links: Turner syndrome" and "Society guideline links: Growth hormone deficiency and other growth disorders".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces ar e
written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles
are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces ar e longer, more sophisticated,
and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and ar e comfortable with some
medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient
education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

● Basics topic (see "Patient education: My child is short (The Basics)")

SUMMARY AND RECOMMENDATIONS

● Short stature is defined as height that is 2standard deviations (SD) or more below the mean height for children of that sex and chronological age in a given
population. This translates to a height that is below the 2.3rd percentile. The clinical significance of theshort stature depends on many factors, including genetic
potential and changes in stature over time (height velocity). (See 'Is the child short?' above.)

● Determination of the child's growth, or height velocity (HV), is an essential component of the evaluation for short stature. For children two years and older, growth
failure is suggested by a growth pattern that has deviated downwards across two major height percentile curves, or by growth slower than the following ar tes:

• Age two to four years: HV less than 5.5cm/year (<2.2 inches/year)

• Age four to six years: HV less than 5cm/year (<2 inches/year)

• Age six years to puberty:

- HV less than 4 cm/year for boys (<1.6 inches/year)

- HV less than 4.5 cm/year for girls (<1.8 inches/year)

(See 'Is the child's height velocity impaired?' above.)

● An estimate of a child's adult height potential can be obtained by calculation of the midparental height (target height), adjusted for the sex of the child calculator
( 4).
For boys and girls, 8.5 cm (3.3 inches) oneither side of this calculated value represents the 3rd to 97th percentiles for anticipated adult height. (See 'Is the child’s
growth within the range for the family?'above.)

● The history and physical examination should include (see 'Additional evaluation for causes of short stature' above):

• Family history of growth and pubertal onset

• Review of systems for features suggestive of gastrointestinal, pulmonary, immunologic, or other systemic disease

• Dysmorphic features, especially webbed neck, cubitus valgus, and absent puberty in girls (suggests Turner syndrome), or disproportionate short stature (ie, short
limbs compared with trunk).
 ● The two most common causes of short stature are familial (genetic) short stature and constitutional delay of growth and puberty (CDGP), which are variants of
normal growth. These growth patterns often can be distinguished fr
om one another, but some children have features of both (table 2). (See 'Are there features that
suggest that this is a normal variant of short stature?' above.)

● Important pathologic causes of growth failure that may present with short stature and/or delayed puberty include Crohn disease, celiac disease, and Turner syndrome
(table 1). (See 'Are there features suggesting pathologic growth failure?' above.)

● Laboratory evaluation for a child with short stature depends on the results of the above evaluation (algorithm 1).

• For children with short stature, normal growth rate (eg, HV at least 5cm/year between four and six years of age, and at least 4cm/year between six years and
puberty) and no other symptoms, we suggest a basic evaluation including bone agedetermination. The bone age er sult can then be used to refine the estimate
for the child's adult height and also informs the evaluation for possible causes of short stature. (See 'Bone age determination' above and 'Laboratory and imaging
studies' above.)

• Children with severe short stature (eg, height ≤-2.5 SD [0.6th percentile]) or growth failure should be further evaluated with a complete blood count (CBC),
erythrocyte sedimentation rate (ESR), tissue transglutaminase (tTG) immunoglobulin A (IgA), creatinine, electrolytes, thyroid stimulating hormone (TSH), free
thyroxine (T4), insulin-like growth factor-I (IGF-I), and insulin-like growth factor binding protein-3 (IGFBP-3). A karyotype should be performed in all girls with
unexplained short stature (to evaluate for Turner syndrome), and in short boys with associated genital abnormalities. Abnormalesults r of these testsand/or
symptoms are signs a disorder causing growth failure warrants further investigation. (See 'Laboratory and imaging studies'above and "Causes of short stature",
section on 'Endocrine causes of growth failure'.)

Use of UpToDate is subject to the Subscription and License Agreement.

Topic 5834 Version 30.0

GRAPHICS

Estimates for normal growth rates in children

Normal length or height at v arious ages during childhood, and the gr owth r ate between those timepoints, ar e approximated b y
multiples of fiv e when measur ed in centimeters (this is sometimes termed the "rule of fiv es"). Actual height and gr owth r ate in a
healthy child can v ary substantially ar ound these appr oximations.

* Growth rates may be considerably higher in the late r end of this age r ange for childr en who have entered their puber tal growth spur t. In girls,
the puber tal growth spur t typically star ts around age 10, but ma y start as early as age 8 in early-maturing girls. In bo ys, the puber tal growth
spurt typically star ts around age 12, but ma y start as early as age 10 in early-maturing bo ys.

Graphic 70382 V ersion 7.0

Algorithm for the evaluation of a child with short stature*

This algorithm describes the detailed e valuation of a child with shor t statur e. Some components of the e valuation can r easonably be per formed in the primar y care setting, including initial interpr etation
and height v elocity, and initial labor atory screening for an underlying systemic disease, if suspect ed based on sympt oms. Other components of the e valuation, including bone age interpr etation a nd the
detailed e valuation for causes of shor t statur e, are typically per formed b y a pediatric endocrinologist, if a vailable.

GDPP: gonadotr opin-dependent pr ecocious puber ty (central sexual precocity); GIPP: gonadotr opin-independent pr ecocious puber ty (peripheral sexual precocity); ISS: idiopathic shor t stature; SD: standar d deviation; CDGP:
constitutional dela y of growth and puber ty; GH: growth hormone.
* Short stature is defined as height that is 2 SD or mor e below the mean (Z-scor e ≤–2) for childr en of the same sex and chr onologic age in a giv en population. This corr esponds to a height that is below the 2.3r d percentile.
¶ Decreased height v elocity (HV ) is indicated b y a growth rate <5.5 cm/y ear from 2 to 4 years of age; <5 cm/y ear from 4 to 6 years of age; <4 cm/y ear from age 6 years to puberty; or crossing two major per centile lines on a
standard height-by-age char t.
Δ Systemic diseases ma y present with signs and sym ptoms either befor e or after the y affect height or height v elocity. This is especially true for inflammat ory diseases (Cr ohn disease, juv enile idiopathic ar thritis) or any
disorder that affects nutrition.
◊ Bone age determination r equires expert interpretation of the hand r adiograph using the Gr eulich and P yle Atlas. If bone age is dela yed or advanced, the HV per centile and pr ojected height should be r ecalculated b ased on
bone age.
§ Delayed or advanced bone age (BA) is defined as a BA that is 2 SD or mor e below or abo ve the mean, r espectively. This translates to difference beween BA and chr onological age (CA) of appr oximately 12 months between
2 and 4 years of CA, 18 months between 4 and 12 y ears, and 24 months after age 12.
¥ Evaluation for systemic, endocrine, or genetic disor der includes a focused hist ory and physical examination (r efer to topic review on evaluation for shor t stature). In addition, patients with gr owth failure usually should ha ve
laboratory screening including a complete blood count (CBC ), erythrocyte sedimentation r ate (ESR) or C-r eactive protein (CRP), tissue tr ansglutaminase (tT G), creatinine, electr olytes, bicarbonate, calcium, phosphate, alkaline
phosphatase, albumin, thyr oid stimulating hormone (T SH), free thyroxine (T4) and insulin-lik e growth factor-I (IGF-I), and insulin-lik e growth factor binding protein-3 (IGFBP-3). A kar yotype should be per formed in all girls with
unexplained shor t stature, and in shor t boys with associated genital abnormalities [1]. Some or all of this e valuation is typically per formed by a pediatric subspecialist, but v aries with the child' s presenting sympt oms and the
clinical setting.
‡ Constitutional dela y of growth and puber ty (CDGP) is particularly likely if there is a family hist ory of this growth pattern (eg, r elatively late puber ty).

Reference:
1. Cohen P, Rogol AD, Deal CL, et al. Consensus statemen t on the diagnosis and tr eatment of childr en with idiopathic shor t stature: A summar y of the Growth Hormone Resear ch Society, the Lawson Wilkins P ediatric
Endocrine Society, and the European Society for P aediatric Endocrinology W orkshop. J Clin Endocrinol Metab 2008; 93:4210.

Graphic 94743 V ersion 5.0

Length-for-age percentiles, boys birth to 24 months, WHO growth standards

WHO: World Health Or ganization.

Reproduced from: Centers for Disease Contr ol and Prevention based on data fr om the WHO Child Gr owth Standar ds.

Graphic 67950 V ersion 3.0

Length-for-age percentiles, girls 0 to 24 months, WHO growth standards

WHO: World Health Or ganization.

Reproduced from: Centers for Disease Contr ol and Prevention based on data fr om the WHO Child Gr owth Standar ds.

Graphic 80511 V ersion 3.0

Height measurement technique

The child' s shoes and any hats or hair ornaments ar e removed. The child faces awa y
from the wall with the heels t ogether and the bac k as str aight as possible. The head,
shoulders, butt ocks, and heels should be in conta ct with the v ertical sur face. With the
child looking str aight ahead, the head pr ojection is placed at the cr own of the head. The
child steps awa y from the wall, and the height measur ement is r ecorded to the near est
0.1 cm.

Graphic 56127 V ersion 1.0

Stature-for-age percentiles, boys, 2 to 20 years, CDC growth charts: United States

CDC: Centers for Disease Contr ol and Prevention.

From National Health Center for Health Statistics in co llaboration with the National Center for Chr onic Disease Pr evention
and Health Promotion (2000).

Graphic 63399 V ersion 5.0

Stature-for-age percentiles, girls, 2 to 20 years, CDC growth charts: United States

CDC: Centers for Disease Contr ol and Prevention.

From National Health Center for Health Statistics in co llaboration with the National Center for Chr onic Disease
Prevention and Health Pr omotion (2000).

Graphic 77249 V ersion 4.0

Height velocity in American boys

Height v elocity b y age for A merican bo ys. The m ain set of cur ves (black lines) is center ed on the
population with a verage timing of peak gr owth v elocity (ar ound 13.5 y ears for bo ys) and show an
approximate tr ajectory for individual childr en with this a verage puber tal timing. The two other cur ves
outline a tr ajectory (50th per centile) for a child w ith 'early' (solid blue) or 'late ' (solid or ange) timing of
peak gr owth v elocity.
Other height v elocity cur ves (not shown her e) have been de veloped that r eflect population a verages;
those cur ves are substantially flatter than the tr ajectory followed b y any individual patient [1]. Those
curves are based on data fr om a mor e recent and ethnically div erse population of childr en, and ar e
valuable for understanding o verall growth patterns in the population, but ar e less appr opriate for
evaluation of the gr owth of an individual patient.

SD: standard deviations.

Reference:
1. Kelly A, Winer KK, Kalkwar f H, et al. Age-based r eference ranges for annual height v elocity in US childr en. J Clin
Endocrinol Metab 2014; 99:2104.
Reproduced with permission fr om: Tanner JM, Da vies S. Clinical longitudinal standar ds for height and height v elocity
for North American childr en. J Pediatr 1985; 107:317. Cop yright © 1985 Else vier.

Graphic 96367 V ersion 4.0

Height velocity in American girls

Height v elocity b y age for A merican girls. The ma in set of cur ves (black lines) is center ed on the
population with a verage timing of peak gr owth v elocity (ar ound 11.5 y ears for girls), and show an
approximate tr ajectory for individual childr en with this a verage puber tal timing. The two other cur ves
outline a tr ajectory (50th per centile) for a child w ith 'early' (solid blue) or 'late ' (solid or ange) timing of
peak gr owth v elocity.
Other height v elocity cur ves (not shown her e) have been de veloped that r eflect population a verages;
those cur ves are substantially flatter than the tr ajectory followed b y any individual patient [1]. Those
curves are based on data fr om a mor e recent and ethnically div erse population of childr en, and ar e
valuable for understanding o verall growth patterns in the population, but ar e less appr opriate for
evaluation of the gr owth of an individual patient.

SD: standard deviations.

Reference:
1. Kelly A, Winer KK, Kalkwar f H, et al. Age-based r eference ranges for annual height v elocity in US childr en. J Clin
Endocrinol Metab 2014; 99:2104.
Reproduced with permission fr om: Tanner JM, Da vies S. Clinical longitudinal standar ds for height and height v elocity
for North American childr en. J Pediatr 1985; 107:317. Cop yright © 1985 Else vier.

Graphic 96366 V ersion 3.0

Estimated projected height using current growth channel

Projected height pr ovides a crude estimate of adult height in healthy childr en. Projected height is
determined b y extrapolating the child' s growth al ong the curr ent channel t o the 18- t o 20-y ear mark. In the
example abo ve, the six-y ear-old bo y is 43.5 inches (point A) which is at the 10th per centile. His pr ojected
adult height is the 10th per centile height for a 20-y ear-old (point B): 66 inches.
Projected height is only weakly corr elated with actual adult height, especially for y oung childr en, and has
minimal pr edictiv e value for childr en younger than two y ears. Pr ojected height does not pr ovide a valid
estimate of adult height in childr en with dela yed or adv anced bone age, or a v ariety of pathologic causes
of shor t statur e.

From: National Health Center for Health Statistics in co llaboration with the National Center for Chr onic Disease
Prevention and Health Pr omotion.

Graphic 64811 V ersion 4.0

Chronological age versus bone age for boys

This char t depicts bone age as compar ed with chr onological age in bo ys. The normal r ange is r epresented b y 2 standar d
deviations (SD) abo ve and below the mean (white ar ea on this char t). Bone age is dela yed if it is below this thr eshold (blue
area), and adv anced if it is abo ve this thr eshold (gr een ar ea). In clinical pr actice, a bone age that is 20 per cent below or abo ve
the chr onological age is consider ed abnormal. These data ar e based on the Brush F oundation Study , performed in well-
nourished Caucasian childr en in the 1930s and 1940s.

Reference:
1. Greulich WW, Pyle SI. Radiogr aphic Atlas of Skeletal Development of the Hand and W rist, 2nd Edition, Stanfor d, CA: Stanfor d University
Press and London, UK: Oxfor d University Press, 1959.
Data from: Gaskin CM, Kahn SL, Ber tozzi JC, Bunch PM . Skeletal development of the hand and wrist. Oxfor d University Press, New York 2011.
p.8.

Graphic 94179 V ersion 3.0

Chronological age versus bone age for girls

This char t depicts bone age as compar ed with chr onological age in girls. The normal r ange is r epresented b y 2 standar d
deviations (SD) abo ve and below the mean (white ar ea on this char t). Bone age is dela yed if it is below this thr eshold (blue ar ea),
and adv anced if it is abo ve this thr eshold (gr een ar ea). In clinical pr actice, a bone age that is 20 per cent below or abo ve the
chronological age is consider ed abnormal. These data ar e based on the Brush F oundation Study , performed in well-nourished
Caucasian childr en in the 1930s and 1940s.

Reference:
1. Greulich WW, Pyle SI. Radiogr aphic Atlas of Skeletal Development of the Hand and W rist, 2nd Edition, Stanfor d, CA: Stanfor d University
Press and London, UK: Oxfor d University Press 1959.
Data from: Gaskin CM, Kahn SL, Ber tozzi JC, Bunch PM . Skeletal development of the hand and wrist. Oxfor d University Press, New York 2011.
p.8.

Graphic 94180 V ersion 2.0

Major causes of short stature
 
Normal variants of gr owth
Familial shor t stature*
Constitutional dela y of
growth and puber ty*
Small for gestational age
infant, with catch-up gr owth
Pathologic causes of gr owth failure
Systemic disor ders or pr ocesses with secondar y effects on growth
Undernutrition
Glucocor ticoid therapy
Gastrointestinal disease
(especially Crohn's
disease and celiac
disease)
Rheumatologic disease
(especially systemic
onset juvenile idiopathic
arthritis [JIA])
Renal disease
(chronic kidney disease,
renal tubular acidosis)
Cancer
Pulmonary disease (eg,
cystic fibrosis, immune
deficiencies with
recurrent pulmonar y
infections, or se vere
asthma)
Immunologic disease
Endocrine causes of gr owth failur e
Hypothyroidism
Cushing syndr ome
Growth hormone
deficiency
Precocious puber ty
Distinguishing features
Short parent(s), often below the
10th percentile. Adult height
short for population, but within
the range predicted by parents'
height.
Normal height for bone age but
not for chronological age. Often
family history of delayed
growth and/or puber ty. Adult
height usually normal.
Most SGA infants catch up b y
two years of age; the r emainder
have slower or absent catch-up
growth that can be consider ed
pathologic
Low weight-for-height
Growth effects are dose-
related, greatest with systemic
dosing. Mild eff ects may occur
with long-term use of inhaled
glucocorticoids
GI symptoms (diarrhea,
abdominal pain). Cr ohn's
disease may have oral ulcers
and anal fissur es/skin tags.
Fever, arthralgias, rash,
lymphadenopathy
Growth impairment ma y
precede the diagnosis of CKD .
Other symptoms of CKD ma y
include polyuria, edema,
elevated creatinine, tea-color ed
urine, hyper tension.
Any cancer: multiple
mechanisms for gr owth
failure, including decr eased
intake, increased energy
needs
Brain cancer: dir ect effects
on hypothalamic-
pituitary function
Cancer treated with CNS
radiotherapy or
chemotherapy: may have
direct effects on GH
production, with late eff ects
on growth
Respiratory symptoms,
recurrent infections
In CF: steatorrhea/GI
symptoms, failure to
thrive
Recurrent infections
(manifestations vary depending
on type of immunodeficiency)
Sluggishness, lethar gy, cold
intolerance, constipation,
decreased reflexes
Obesity with centr al fat
distribution; buffalo hump;
purple striae
Progressive growth failure. May
also have symptoms of other
pituitary hormone deficiencies.
Virilization
Typical evaluation
Hx, PE, bone age
Hx, PE, bone age
Be alert for the possibility
of underlying systemic
disease
Lab screening if height
velocity is slow
Hx, PE, bone age
For prematurely born
infants, adjust height for
gestational age (up t o 1
year of chronological
age)
Hx (including dietar y and social
hx), PE, bone age
Hx, PE
Assess contribution of
underlying disease t o
growth deficit
Hx, PE, bone age
Screening lab tests
including CBC, ESR or
CRP, celiac serologies
Hx, PE, bone age
Screening lab tests
including CBC and ESR or
CRP, ANA, RF
Hx, PE, bone age
Screening lab tests
including BUN, cr eatinine,
and urine analysis
Hx, PE, bone age
 
For children with history of
cancer, or with CNS sympt oms
or hypothalamic-pituitar y
disease: screening lab tests t o
assess pituitar y function (fr ee
T4, IGF-I, IGFBP-3), +/– head
MRI with contr ast. 
Hx, PE, bone age. T est for CF
and immune deficiencies.
Hx, PE, bone age
Workup for immune
deficiencies (r efer to
topic review on childr en
with recurrent infections)
Hx, PE, bone age
TSH and free T4. If
hypothyroidism is centr al
(low TSH and low T4),
also assess for other
pituitary hormone
deficiencies.
Hx, PE, bone age
24 hour urine collection
for free cortisol
Hx, PE, bone age
Measurements of GH,
IGF-I, and IGFBP-3 Δ
Hx, PE, bone age
Δ
Treatment Bone age Height velocity
None needed. Reassur ance; Normal Low-normal
monitor growth. eg, from age 6 until puber ty:
Girls about 4 t o 5 cm/year
Boys about 3.5 t o 4.5
cm/year
None needed. Reassur ance; Delayed Slow during first thr ee to five
monitor growth; +/– treatment years of life; normal during
with sex steroids during childhood. Puber tal growth
puberty. spurt is delayed but prolonged,
often resulting in normal adult
height.
Monitor growth to distinguish Normal Normal
from the 10 per cent of SGA
infants who do not ha ve catch-
up growth
Reverse nutritional deficit Delayed or normal Slow (eg, <4 cm/y ear)
Minimize glucocor ticoid dose Delayed Slow
or give on alternate da ys if
feasible; consider alternate
drugs
Diagnose and tr eat underlying Delayed Slow
disease, improve nutrition,
avoid glucocor ticoids
Diagnose and tr eat underlying Delayed Slow
disease, improve nutrition,
avoid glucocor ticoids
Diagnose and tr eat underlying Delayed Slow
disease, maximiz e nutrition; GH
if needed
Ensure adequate nutrition; tr eat Delayed Slow
any secondar y pituitary
hormone deficiencies (eg, GH
deficiency)
Diagnose and tr eat underlying Delayed Slow
disease, ensur e adequate
nutrition, avoid glucocor ticoids
Diagnose and tr eat underlying Delayed Slow
disease
Thyroid hormone r eplacement Delayed Slow
Diagnose and tr eat underlying Delayed Slow
disease
rGH Delayed Slow
Treatment depends on type of Advanced Initially fast, then st ops early
 LH, FSH Δ precocious puber ty

Genetic diseases with primar y effects on gr owth

Turner syndrome Square "shield" chest, webbed Karyotype analysis (for 45,X, Estrogen, GH Normal Slow
neck, cubitus v algus ◊, genu structural abnormality of X, or
valgum, Madelung deformity §. mosaic)
Up to 50 percent have only
short stature and absent
pubertal development.

SHOX mutations May have isolated shor t stature Molecular genetic testing for Consider GH Normal Slow
(usually stocky appearance) OR SHOX abnormalities
additional features: shorter
forearms and lower legs,
cubitus valgus ◊, Madelung
deformity §, high arched palate

Noonan syndr ome Minor facial dysmorphism, Molecular genetic testing for Consider GH Normal Low-normal or slow
heart disease, intellectual PTPN11, SOS1, and other
disability, webbed neck, pectus genes Δ
excavatum, cryptorchidism

Silver-Russell syndr ome
Severe intrauterine growth Clinical diagnosis, suppor ted by Consider GH Normal Slow
restriction and postnatal molecular genetic testing Δ
growth retardation. Prominent
forehead, triangular face,
downturned corners of the
mouth, and body asymmetr y
(hemihyper trophy).

Skeletal dysplasias

Achondroplasia Short arms and legs, midface
hypoplasia, trident hands. Most
cases identified pr enatally or in
early infancy.
Clinical diagnosis
Genetic testing for
FGFR3 mutations is
available Δ
Management of complications,  Mildly delayed Slow 
which may include
craniocervical junction
compression, sleep
apnea, spinal stenosis.

Hypochondroplasia Short arms and legs
similar to but milder than
in achondroplasia; lumbar
lordosis. May include
macrocephaly, epilepsy.
Skeletal survey Surveillance for spinal stenosis,  ? Normal Slow 
with surgery as needed. 
Genetic testing for FGFR3
mutations (positiv e in 70
percent)

Spondyloepiphysial Heterogenous manif estations;
dysplasia  trunk disproportionately
shortened compar ed with
limbs; may develop scoliosis,
kyphosis and osteoar thritis.
Anthropometrics; sk eletal Surveillance for spinal ? Normal Slow
survey  disorders and
osteoarthritis, with sur gery as
needed.

Osteogenesis Children with moder ate to Skeletal survey Bisphosphonates, fr acture Normal  Low-normal or slow 
imperfecta severe disease are usually management 
recognized by recurrent
fractures but also de velop
short stature. Blue sclerae,
scoliosis, and hearing loss ma y
be present.

Hx: history; PE: physical examination; CBC: complete blood count; ESR: er ythrocyte sedimentation r ate; CRP: c-reactive protein; IGF-I: insulin-lik e growth factor I; IGFBP-3: insulin-lik e growth factor binding protein 3;
GH: growth hormone; LH: luteinizing hormone; FSH: follicle-stimulating hormone; SHO X: short stature homoeobox; SGA: small for gestational age; GI: gastr ointestinal; CF: cystic fibr osis; CNS: centr al nervous
system; CKD: chr onic kidney disease.
* Some patients ha ve features of both familial shor t stature and constitutional dela y of growth and puber ty (CDGP).
Δ Evaluation of patients in whom this disor der is suspected usually is per formed by a subspecialist (ie, a P ediatric Endocrinologist, Gastr oenterologist, or Geneticist).
◊ Cubitus valgus is an incr eased carrying angle of the arm.
§ Madelung deformity is focal dysplasia of the distal r adial physis, which can r esult in a prominent ulna and wrist pain.

Graphic 94176 V ersion 4.0

Differential features of familial short stature and constitutional delay of growth and puberty

Feature Familial short stature Constitutional delay

Parents' stature Small (one or both) Average

Parents' puber ty Usual timing Often delayed

Birth length Normal or low-normal Normal

Growth (zero to two years) Normal Slow from mid-infancy t o mid-childhood

Growth (two years to puberty) Normal Slow

Bone age Normal Delayed

Timing of puber ty Normal Delayed

Pubertal growth Rate low-normal Growth spur t delayed; rate slightly diminished

Adult height Short Normal

Graphic 51582 V ersion 5.0

Optic nerve hypoplasia

At first glance, the disc ma y appear pale but the a ctual disc substance is within this pale
area. Arr ows indicate actual ner ve borders.

Courtesy of Karl C Golnik, MD .

Graphic 70125 V ersion 1.0

Clinical features of Turner syndrome

Eleven-year-old with classical appear ance of 45,X T urner syndr ome, including shor t
stature, lack of br east de velopment, and shield chest with widely spaced nipples.
Additional f eatures ma y include webbed neck, cu bitus v algus, and shor tened four th
metatarsals.

Reproduced with permission fr om: Rebar RW, Paupoo AAV. Puberty. In: Berek and Novak's
Gynecology, Berek, JS (Ed), Philadelphia: Lippincott Williams & Wilkins, 2012. Cop yright © 2012
Lippincott Williams & Wilkins. www.lww.com.

Graphic 91041 V ersion 7.0

Madelung deformity of the forearm

(A, B) Clinical phot ographs of a patient with Mad elung deformity . Note the seemingly pr ominent u lnar head and
apparent volar subluxation of the wrist on the for earm.

Reproduced with permission fr om: Waters PM, Bae DS. P ediatric Hand and Upper Limb Sur gery. Lippincott W illiams & Wilkins,
Philadelphia 2012. Cop yright © 2012 Lippincott Williams & Wilkins. www.lww.com.

Graphic 94419 V ersion 3.0

Madelung deformity radiographs

Radiogr aphs of a Madelung deformity .

(A) Anteroposterior view .
(B) Later al view.

Reproduced with permission fr om: Waters PM, Bae DS. P ediatric Hand and Upper Limb Sur gery. Lippincott W illiams & Wilkins,
Philadelphia 2012. Cop yright © 2012 Lippincott Williams & Wilkins. www.lww.com.

Graphic 94420 V ersion 3.0