DR EDE OSITA

MODERATOR:DR DURU NE

SKELETAL DYSPLASIAS
OUTLINE

Introduction
Anthropometry of skeletal dysplasia
(SD)
Classification of SD
Diagnosis of SD
Some common SD
Differential diagnosis
treatment
 Prevention
Prognosis
Future trends
Introduction

SD is a heterogeneous group of genetic

disorders xterised by abnormal growth
and modeling of bone and/or cartilage.

Frequently result in dwarfism

>350 SD

Many of the mutation are being unraveled

 Relatively rare( orphan disease)

Manifestations are protean: peri-

natal death to mild symptoms in
adulthood

Short stature, angular deformities,

osteoarthritis ,spine deformities etc
are of orthopedic concerns
 Achondroplasia is the commonest
non-lethal SD while thanatophoric
dwarfism is the commonest lethal SD.

Genetic counseling is possible to

affected patients

Goal of management is to achieve an

independent adult livelihood.
 Historical perspective-
Prior to 70s all disproportionate short
stature were regarded as achondroplastic
dwarfs

Later classification became more

descriptive

Discovery of genes led to genetic

classification
Anthropometry of SD

NORMAL UPPER SEGMENT:LOWER

SEGMENT RANGES from 1.5:1 in infancy to
1:1 at puberty.

Arm span=height

Short stature = 3 or more std dev. Below

the height for age and sex

Proportionate short stature= midget

 Disproportionate short stature =dwarfism

Rhizomelia= short proximal segments

Mesomelia= short middle segments

Acromelia= short distal segments

Micromelia= all segments

Amelia= complete absence

Classification of SD

Genetic classification- based on the

mutation

By the international working group

on bone dysplasias.

Not diagnostically helpful to the

clinician
Genetic Defects in Skeletal
Dysplasia- matrix proteins
?Type I collagen : OI, EDS type VII, Caffey

?Type II collagen : SEDC, Kniest, Stickler

?Type III collagen : EDS

?Type IX collagen : MED

?Type X collagen : MCD Schmid type

?Type XI collagen : Stickler, OSMED

?COMP : PsACH, MED

?Fibrillin : Marfan
Receptor

?FGFR3 : ACH, HCH, TD

?PTH/PTHrP receptor : MCD Jansen type

?GNAS1 : McCune-Albright syndrome

Transcription factor
?Cbfa1 : CCD
Others
?Cell memb sulfate transporter : DTD
?Enzymes : MPS
 Clinical classification-
Based on the radiographic and physical findings
of which bones are involved

-Predominantly epiphyseal

-predominantly metaphyseal

-predominantly diaphyseal

-associated axial involvement

 -combined dysplasias

-dysplasias with increased bone

density

-dysplasias with decreased bone

density

-storage disorders (MPS)

Predominantly epiphyseal

Multiple epiphyseal dysplasia

Dysplasia epihysealis
hemimelica( Trevors dx)

Chondrodysplasia punctata
 Xterised by

Short limb dwarfism

Angular joint deformities

Precocious osteoarthritis
Predominantly physeal/metaphyseal

Hereditary multiple exostosis

Achondroplasia

Hypochondroplasia

Metaphyseal chondrodysplasia

Dyschondroplasia

Multiple enchondromatosis
 Xterised by-

Severe short stature

Articular cartilage normal

Predominantly diaphyseal

Diaphyseal dysplasia

Pyknodyostosis

Melorheostosis

Shortening not severe

 Each of the above can have significant
involvement of the axial skeleton-

Spondylo-epihyseal dysplasia

Spondylo-metaphyseal; dysplasia

SEMD
 MIXED DYSPLASIAS-

Cleido-cranial dysplasia

Cranio-facial dysplasia

Nail-patella syndrome
 Dysplasia with increased bone density-

Osteopetrosis

Dysplasia with decreased bone density-

Osteogensis imperfecta, fibrous dysplasia

Dysplasia due to storage diseases-

MPS- hurler,hunter,morqiuo
Diagnosis

Pre-natal diagnosis-

Ultrasound femoral length for age

Chorionic villus sampling- 10-12th week

Amniocentesis- 12-15th week

Pre-implantation genetic diagnosis

Enables decision regarding delivery and abortion

 Childhood and adult-

History:

Complaints- short stature, angular

deformities, back pain, knee pain,
fractures

Course- present at birth(achondroplasia) or

not(hypochondroplasia)
 Cause- family history, stillbirths,
miscarriages, drugs, illness, nutrition,
supplements

Complications- pulmonic dysfunction,

deafness, limb weakness,
depression, intelligence
Care- vit D, calcium etc
 PE-

GE- obvious shortness, sclera, head, face,thorax

Anthropometry- height, arm span, UBS:LBS.

Different segments of the limb- trident hand,

polydactyl

Back kyphosis etc

Joints.
Investigations

AP, lateral, towne view of the skull

AP, lateral entire spine

AP pelvis and extremities

AP hands and feet

Pre-pubertal x-rays are more helpful

 Pathognomic signs

Punctate calcification of epihyses

Candle stick appearnace

Over-mineralisation

Multiple epihyseal distortions

Multiple fractures
 Spinal deformities

Vertebral anomalies

Limb segments involved

Flexion-extension view in suspected

atlanto-axial instability
 MRI spinal stenosis

Biopsy growth plate, iliac apophysis

Molecular diagnosis
Common skeletal dysplasias

1.Achondroplasia-

Commonest non-lethal dysplasia

Autosomal dominance with high penetrance

FbGF3R mutation

Rhizomelic short limb dwarfism

 Normal intelligence and life
expectancy

Short stature, genu vara, c1/c2

instability, spinal stenosis

Features present from birth- large

skull ,frontal bossing, flat nasal
bridge
 2.hypochondroplasia

Normal at birth

Features begin at 2 years

Normal head and face

No trident hand
 3.MED-
Autosomal dominant

Diffuse epihyseal changes in long

bones

Perthes like picture on x-rays

Precocious arthritis
 OI-

4 types described by sillence

Newer types added

Type 1 collagenopathy

1- mild and commonest, blue sclera, multiple

fractures

2- perinatal lethal
 Types 3 &4- severe deforming types,
wheelchair bound by puberrty

Fractures, short stature, limb

deformities, dentinogenesis
imperfecta, scoliosis, deafness.
TREATMENT

Requires understanding of the medical,

surgical and psychosocial challenges

Communication with parents, patients is

the key

Goals of treatment must be outlined and

discussed

Most lead a relatively normal life

 Multidisciplinary- physicians, orthopedists,
psychologists, neurologists, neurosurgeons, ENT
etc

Orthopedic problems

Shortening- lengthening ( ?GH)

Angular deformities- corrective osteotomies

Osteoarthritis- arthroplasties
 Spinal stenosis- decompression

C1/C2 instability fusion

Multiple fractures treatment( load sharing devices

better)

Other problems that require other specialists-

Deafness

Hydrocephalus
 Depression

Respiratory problems

Obesity risk factor for cord

compression
 Prevention-

Education of parents to avoid contact

sports in children with OI.

Bisphosphonates in OI.

Genetic counseling for affected

individuals
Differential diagnosis

Metaphyseal dysplasia- Rickets,

hypophosphatasia, Physeal injury

MED- perthes

SED- MPS

OI- child abuse

Prognosis

Achondrogenesis and thanatophoric

dwarfism are the commonest lethal
dysplasias

Most non-lethal dysplasia lead a

normal life and have normal fertility
Future trends

Gene therapy- plasmids.

Registries

International skeletal dysplasia

registries (http://www.csmc/skeletal
dysplasia)

European skeletal dysplasia network

( http://www.esdn-org).
Conclusion

Though rare , SD is a big source of

concern to the parents and the
patient. Its our job to educate them
on issues such as fertility, life
expectancy, inheritance patterns and
likely problems of each. This requires
understanding and appreciation of
this entity. There are support groups
available that patients can benefit
from.
Thank you.
references

Louis S,David W & Selvadurai N. Apleys

System of Orthopedics & fractures,
9thedition, Hodder Arnold, 2010.

Deborah krakow,david l rimoin. The

skeletal dysplasia. Genet med
2010:12(6):327-341.

Harold chen, luis o. rohena. Skeletal

dysplasia.medscape.