Clinical characteristics: Focal dermal hypoplasia is a multisystem disorder characterized primarily by involvement of the skin, skeletal system, eyes, and face. Skin manifestations present at birth include atrophic and hypoplastic areas of skin; cutis aplasia; fat nodules in the dermis manifesting as soft, yellow-pink cutaneous nodules; and pigmentary changes. Verrucoid papillomas of the skin and mucous membranes may appear later. The nails can be ridged, dysplastic, or hypoplastic; hair can be sparse or absent. Limb malformations include oligo-/syndactyly and split hand/foot. Developmental abnormalities of the eye can include anophthalmia/microphthalmia, iris and chorioretinal coloboma, and lacrimal duct abnormalities. Craniofacial findings can include facial asymmetry, notched alae nasi, cleft lip and palate, and pointed chin. Occasional findings include dental anomalies, abdominal wall defects, diaphragmatic hernia, and renal anomalies. Psychomotor development is usually normal; some individuals have cognitive impairment.
Diagnosis/testing: Focal dermal hypoplasia can be diagnosed based on clinical findings in individuals with classic ectodermal findings and characteristic limb malformations. Molecular genetic testing may be useful to confirm the diagnosis in these individuals and is used to establish the diagnosis in individuals in whom the clinical findings are inconclusive.
Management: Treatment of manifestations: Care by a dermatologist for painful and pruritic erosive lesions that are prone to infection; referral to an otolaryngologist or gastroenterologist for evaluation and management of large papillomas of the larynx and/or trachea or esophagus causing gastroesophageal disease (GERD); referral to a physical/occupational therapist and hand surgeon for management of hand and foot malformations; standard protocols for management of structural abnormalities of the eyes and kidneys and diaphragmatic hernia and abdominal wall defects.
Prevention of secondary complications: Preoperative evaluation by an otolaryngologist for hypopharyngeal and/or tonsillar papillomas.
Surveillance: Routine follow up with a dermatologist; routine evaluations for scoliosis, particularly in individuals with costovertebral segmentation abnormalities; routine monitoring of growth and body composition to determine need for nutritional intervention; regular eye examinations; routine screening for cognitive, emotional, behavioral, and adaptive issues.
Genetic counseling: Focal dermal hypoplasia is inherited in an X-linked manner. Females (90% of affected individuals) are heterozygous or mosaic for a PORCN pathogenic variant; live-born affected males (10% of affected individuals) are mosaic for a de novo PORCN pathogenic variant. It is presumed that non-mosaic hemizygous males are not viable. Approximately 95% of females with focal dermal hypoplasia have a de novo pathogenic variant; ~5% inherited the pathogenic variant from a parent. The risk that the PORCN pathogenic variant will be transmitted by an affected heterozygous female is 50%; however, because most male conceptuses with a PORCN pathogenic variant are presumed to be spontaneously aborted, at delivery the expected sex ratio of offspring is: 33% unaffected females; 33% affected females; 33% unaffected males. If the affected female is mosaic for a PORCN pathogenic variant, the risk to her female offspring of inheriting the pathogenic variant depends on the level of mosaicism in her germline and can be as high as 50%. Prenatal testing for pregnancies at increased risk and preimplantation genetic testing are possible if the pathogenic variant in the family has been identified.
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