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Modes of Inheritance
Characters of AD diseases
Male to male transmission is present. Both males and females are affected. Affected offspring has chance
(50%) for
both sexes to inherit the mutant gene. The affected individual may inherit the disorder from a parent or develop the condition as a new mutation.
I II
III
IV
Normal female
Affected female
Normal male
Affected male
Examples of AD diseases
Achondroplasia.
Adult polycystic kidney disease.
Familial hypercholesterolemia.
Case (4)
Achondroplasia
It is an AD inherited disease due to disturbance of the growth of bones formed from cartilage.
This produce the characteristic disproportionate short dwarf with shortening of the limbs, hypoplasia of the cranial base, small foramen magnum.
Achondroplasia is an AD disease
Large sized head with prominent frontal and parietal bossing. Saddle-shaped nose. The long bones are short especially at their
proximal parts.
Incidence:
Sex:
The
Macrocephaly may represent mild hydrocephalus relating to a small foramen magnum in addition to the prominent forehead.
Saddle shaped nose due to low nasal bridge with narrow nasal openings.
The long bones are short especially at their proximal parts with accentuation of the physiologic curves of the forearm and lower limbs.
The fingers are short, tapered, similar in length producing short trident hand.
wings.
Characteristics of AR inheritance
The parents are normal while sibs are affected. Consanguinity in parents is more common than in the general population. When only one parent of an affected child is
heterozygote; either:
A new mutation occurred on the gamete inherited from the other parent or; Uniparental disomy when the child inherit 2 copies of the heterozygote mutant allele.
Affected
Consanguineous mating
Examples of AR disorders:
Phenylketonuria.
Galactosemia. Gaucher disease.
Case (5)
A ten month old infant with +ve consanguinity. The baby was normal till the age of five month, then there was gradual increase in the tone of the muscles, appearance of tremors and mental sub normality.
The baby had blonde hair and blue eyes in spite of the black hair and eyes of his parents.
Phenylketonuria (PKU)
Phenylalanine is an essential AA.
It is either used for protein synthesis or degraded via tyrosine pathway and melanin
formation.
Classic PKU
It is an AR disorder. Incidence: 1:10,000-20,000 live births. It is the result of Phenylalanine hydroxylase (PAH) deficiency. The gene is mapped on the long arm of chromosome 12 (12q).
Clinical manifestations
Age of detection:
First week of life (biochemical data) First six months of life (clinical findings)
Main
clinical features:
Small head, blonde hair and blue eyes. Nervous system involvement includes
untreated.
It
is
better
to
offer
neonatal
screening of PKU during the first week of life (3rd day) to avoid the irreversible MR in patients.
Treatment of PKU
Newborn screening for PKU during the 1st week of life. Once it has been determined that the infants PA level is
development.
Maternal PKU
Mental retardation (MR) was almost always present in
II-
III-
IV-
Case (6)
A five year old boy with normal birth weight, normal facial features and normal intelligence till the age of 3
years.
During the last 2 years there were gradual deterioration of his intelligence and coarsening of the facial features.
The mother reported that her brother is crippled with vision and hearing loss.
Clinical abnormalities:
Onset: 2-4 years. Growth deficiency; adult height: 120-150 cm. Performance: Mental and neurologic deterioration. Craniofacial: coarse facial features, full lips,
Macrocephaly, macroglosia.
Joints and bones: partial stiffness of the joints with broadening of the bones. Others: voice. hepatosplenomegaly, deafness, hoarse
Hunter disease
The patient is apparently normal during infancy. Gradual decline in growth rate from 2 to 6 years with gradual coarsening of facial features. Deafness is frequently evident by 2 to 3 years.