Focal Dermal Hypoplasia in Males: A Systematic Review

Focal dermal hypoplasia (FDH) is an X-linked dominant disorder characterized by dermal atrophy, fat herniations, telangiectasias, and pigmentary changes along Blaschko's lines, with multisystem involvement affecting the teeth, nails, eyes, and the skeletal, cardiovascular, and other systems. Initially thought embryonically lethal in males, later reports identified somatic mosaicism as a survival mechanism. The male phenotype remains incompletely defined.

To systematically review reported male FDH cases to consolidate phenotypic patterns, identify key features, and explore genotype-phenotype correlations.

A systematic review of PubMed was conducted with no restrictions on publication date. This review was conducted in accordance with the PRISMA guidelines. Inclusion criteria were case reports and systematic reviews solely investigating FDH or Goltz syndrome.

Forty-five patient cases were identified across 38 case reports and studies. Dermal and skeletal involvement primarily involved extremities. Ophthalmological and dental anomalies, including microphthalmia, colobomas, and enamel defects, were variably present. PORCN variants were confirmed in all but one genetically tested patient, though phenotypes varied. The retrospective nature likely biased toward more severe or unusual presentations.

FDH in males exhibits marked clinical variability. The observed heterogeneity in histopathological findings reinforces the need for flexible diagnostic criteria, with genetic testing for PORCN variants recommended when clinical suspicion remains high. A multidisciplinary approach is recommended, with surveillance of ocular, dental, and skeletal manifestations even in patients with minimal cutaneous findings. Further research into PORCN function and Wnt signaling is needed to refine genotype-phenotype relationships and explore alternative disease mechanisms.