OMIM ID:
Focal Dermal Hypoplasia
Alternate Names
Defective Genes
Clinical Characteristics
Ocular Features
Features have considerable heterogeneity and few patients have all of them. Some ocular abnormalities are found in 40% of patients. Microphthalmia is common and many patients (30%) have colobomas of the iris and choroid. Some patients have dislocated lenses. Distinctive peripheral corneal lesions consisting of discrete vascularized subepithelial opacities have been described. Occasional patients have conjunctival or lid margin papillomas. Strabismus and nystagmus are common.
Systemic Features
This disorder has a wide variety of clinical features and many occur in only a few patients. The skin has focal areas of hypoplasia with hypopigmentation, often appearing in a streak or linear pattern. These areas may be present at birth and contain bullae or urticarial lesions with signs of inflammation. Telangiectases and herniated fat may appear in these areas. Oral, esophageal, and laryngeal fibrovascular papillomas occur but they may also be seen in the perineal, vulvar, and perianal areas. These may be large, friable, and recurrent. The teeth erupt late and are usually hypoplastic. The nails are often dysplastic and the hands and feet may be ‘split’ with syndactyly of the third and fourth fingers giving a ‘lobster claw’ appearance. Polydactyly may be present. Most have thin ‘protruding’ ears. A variety of skeletal anomalies have been reported including absence of metatarsals and metacarpals. A considerable number of patients have mild to moderate mental deficits. Severely affected females may die in infancy.
Genetics
Inheritance
This is considered an X-linked dominant disorder with lethality in males. However, numerous affected males (>30) and rare instances of father-to-daughter transmission have been reported and it has been suggested that half-chromatid mutations or postzygotic somatic mosaicism in these males might be responsible. Mutations in the PORCN gene (Xp11.23) have been associated with FDH.
Pedigree
X-linked dominant, mother affected
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.
X-linked inheritance patterns result from mutations located on the X chromosome. Females have two X chromosomes of which only one carries a mutation in X-linked dominant disorders. This usually results in expression of the disease and women with a single mutation have the disorder caused by the mutation. Half of their offspring, male and female, will inherit the mutation. Men, with only one X chromosome, will always have the condition if they inherit the one with the mutation. Men would transmit it to all of their offspring. Without a modifying normal gene on a second X chromosome, X-linked dominant conditions are frequently lethal in such males. The result is a vertical transmission pattern, usually from female to female.