Diagnostic Considerations
Incontinentia pigmenti (Bloch-Sulzberger syndrome) (OMIM #308300)
Initially, a number of focal dermal hypoplasia (FDH) cases were reported as variants of incontinentia pigmenti because of the marked predilection for females with male mortality in utero, the linear nature of the skin lesions following the Blaschko lines, and an initial inflammatory phase.
As more cases of focal dermal hypoplasia were reported, the two syndromes were noted to be distinct. The clinical history of incontinentia pigmenti includes cutaneous vesiculation and verrucous lesions with persistent whorled hyperpigmentation, which differ from the red, linear, atrophic areas of focal dermal hypoplasia. The histopathologic findings of incontinentia pigmenti are highly characteristic in the early vesicular and verrucous phases. Eye abnormalities characteristically involve the posterior chamber, with microphthalmos as the late end-stage result. In addition, a higher proportion of patients with incontinentia pigmenti have convulsions and neurologic deficits compared with those who have focal dermal hypoplasia. Incontinentia pigmenti is caused by mutations in the gene NEMO/IKK -gamma on chromosome Xq28.
Aicardi syndrome (OMIM #304050)
Aicardi syndrome is an X-linked dominant condition, with the locus Xp22. Mild skin involvement is noted on the head and neck and, sometimes, the shoulders, chest, and limbs. Microphthalmia, corneal opacity, and agenesis of the corpus callosum are observed.
MIDAS syndrome (OMIM #309801)
Microphthalmia, dermal hypoplasia, and aplasia may be confined to the head, neck, and sclerocornea. Microphthalmia occurs with linear skin defects in individuals with distal Xp segmental monosomy, locus Xp22. The phenotype overlaps with those of both Aicardi syndrome and focal dermal hypoplasia. No PORCN mutations are reported.
Delleman syndrome (oculocerebrocutaneous syndrome) (OMIM #164180)
This syndrome is characterized by orbital cysts of microphthalmia, cerebral malformations, and focal dermal hypoplasia (rare).
Goldenhar syndrome (OMIM #164210)
This syndrome, locus 14q23, is associated with the first and second branchial syndrome. Hemifacial hypoplasia, ocular, oral, aural, and vertebral malformations are observed. Cardiac anomalies and frequent mental deficiencies are observed.
Proteus syndrome (OMIM #176920)
Patchy dermal hypoplasia may be seen in the other numerous features of this syndrome. The hallmark of Proteus syndrome is hemihypertrophy, cerebriform plantar lesions, and macrodactyly. Mosaicism for a somatic activating mutation in the AKT1 gene (164730) on 14q32.3 has been identified.
Deletion of band Xp22.2
Four cases have been described with microphthalmia, normal intelligence, and acute weeping linear skin lesions of the face and neck that heal to become hyperpigmented streaks. The hair, teeth, and skeletal system are normal, except for the occasional finding of mild soft-tissue syndactyly. All probands have a deletion of the short arm of the X chromosome that involves Xp22.2.
Adams-Oliver syndrome (OMIM #100300)
Adams-Oliver syndrome is an autosomal dominant condition that involves an association of scalp and skull bone aplasias with distal limb reductions. The skin and eyes are normal. This condition is often associated with cutis marmorata telangiectasia congenita.
Encephalocraniocutaneous lipomatosis (OMIM #613001)
This is a neurocutaneous disorder characterized by ocular anomalies, skin lesions, and central nervous system anomalies. Patients often have profound mental retardation, early onset of seizures, unilateral temporofrontal lipomatosis, ipsilateral cerebral and leptomeningeal lipomatosis, cerebral malformation and calcification, and lipomas of the skull, eye, and heart.
Microphthalmia with linear skin defects (OMIM #309801)
This is an X-linked male-lethal disorder associated with X-chromosomal rearrangements resulting in monosomy from Xpter to Xp22. Features include microphthalmia, sclerocornea, linear skin defects, and agenesis of the corpus callosum. This syndrome has been shown to be related to defects in holocytochrome C synthase (HCCS) gene.
Conradi-Hünermann-Happle syndrome (OMIM #302960)
This syndrome is caused by a mutation of EPB, a neighboring gene that may be affected by a microdeletion, affecting both genes.
Nevus lipomatosus superficialis (Hoffmann-Zurhelle syndrome)
Nevus lipomatosus superficialis is a developmental anomaly of the skin that involves localized groups of soft fleshy nodules, most commonly on the lower trunk and sacral area; these nodules generally are present at birth. Histologically, the lipomatous nodules of focal dermal hypoplasia are similar; but in the lesions of focal dermal hypoplasia, the collagen is attenuated. Other characteristic systemic abnormalities of focal dermal hypoplasia are not present.
Aplasia cutis congenita
In other forms of aplasia cutis congenita, areas of the skin are absent at birth, but none of the other findings of focal dermal hypoplasia occurs.
Differential Diagnoses
-
Typical facial features are asymmetry of the face with mild hemiatrophy, low-set protruding ears, a narrow nasal bridge, a broad nasal tip with unilateral notch of the nasal alae, and a pointed chin. Also note the reticular hyperpigmentation of the skin, sparse hair, and raspberrylike papillomas on the lips.
-
Photograph shows characteristic linear, erythematous, raised and depressed macules that follow the lines of Blaschko. Also note oligodactyly of the hand (entire rays are absent).
-
Photomicrograph shows the histopathologic findings in a skin biopsy sample. The image depicts the characteristic absence of dermal collagen and the accompanying appearance of adipose tissue in the dermis.
-
Characteristic lobster claw deformity.
-
Syndactyly.
-
Image shows oligodactyly of the feet. Also note the reticular erythematous hyperpigmentation on the limbs.
-
Characteristic lesions that follow the lines of Blaschko.
-
Hyperpigmentation that follows the lines of Blaschko on the upper extremity.
-
Slightly raised and pigmented macules and soft tumors are noted on this extremity.
-
Close-up view of reticulate, mildly atrophic, erythematous macules and soft, rounded nodules.
