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Complex mesoectodermal hereditary disorder
characterized by focal dermal atrophy, with herniation of fat-producing
multiple papillomas, in association with skeletal, dental, ocular, and
other anomalies.
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Focal Dermal Hypoplasia (FDH).
[NB: Avoid confusion with Goltz-Gorlin syndrome (inheritable disease
characterized by multiple cutaneous nodules with a tendency to become
malignant).]
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Frequency is approximately 2:100,000 newborns.
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95% sporadic. X-linked dominant with in
utero lethality in males or by a sex-limited dominant gene of variable
expressivity. Gene is located on Xp22.31. Only 10% of cases occur in
males (possibly the result of half-chromatid mutations).
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The underlying molecular defect in FDH is not
clear. Based on the common findings of syndactyly, oligodactyly, and
polydactyly, the fetal expression of FDH is postulated to occur before week
8 of gestation because the hands and feet have differentiated and developed
separate and elongated digits by the eighth week. Because skin and bone
lesions generally follow the lines of Blaschko, mosaicism with random
X-chromosome inactivation is probable. Clinical abnormalities indicate a
profound dysplasia of ectodermal, neuroectodermal, endodermal, and
mesodermal elements. Various in vitro observations of fibroblasts from
lesional skin reveal abnormal growth kinetics of fibroblasts (increase in
the fibroblast doubling time), abnormal glycosaminoglycan metabolism
(decreased accumulation of hyaluronic acid), and absence of basement
membrane type IV collagen. A hypothesis that aberrant dermal fibroblast
growth and altered collagen fibers may be the basis of the skin defects in
FDH has been suggested.
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Usually female gender. Characteristic skin findings are
present at birth (streaky areas of hyperpigmentation, atrophy, and
telangiectasia and groups of soft, yellow-red nodules). Radiologic
examination shows longitudinal striation of the long bones with crossing of the
epiphyses (osteopathia striata). The combination of split-hand with
syndactyly and absence of rays, the so-called lobster-claw hand, is a
striking feature of the disorder.
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Patients with areas of total absence of skin at
birth have been reported. More commonly, skin changes are usually present at
birth or develop shortly thereafter from erythematous areas. Papillomas
usually develop later, involving the mucous membranes or skin. Lesions of
the oropharynx and peritonsillar regions have been described. Laryngeal
papillomas requiring tracheostomy in one case and esophageal papillomas
associated with strictures have been described. In addition, anomalies
involving the hands (syndactyly, polydactyly, camptodactyly, missing digits or
entire hand), skeleton (hypoplasia or aplasia or the truncal skeleton), mouth (lip
papillomas, hypoplastic teeth), and eyes (coloboma of iris and choroid,
strabismus, microphthalmia) have been present in some cases.
Gastroesophageal reflux, short stature, and mental retardation occur in many
patients. Course ...