Phenotypes, Genetics, and Estimated Prevalence of Focal Dermal Hypoplasia (Goltz Syndrome): A Single‐Center Report

ABSTRACT Background Focal dermal hypoplasia (FDH), also known as Goltz syndrome, is a rare ectodermal dysplasia that primarily affects the skin, skeleton, and eyes. It is an X‐linked dominant disorder, predominantly seen in females, caused by pathogenic variants in PORCN. Methods We characterized a case series of four genetically confirmed FDH patients (three females, one male) at Aarhus University Hospital, Denmark. We estimated the FDH prevalence from our local cohort and nationwide registry data. Results Three patients had characteristic dermatological findings suspicious for FDH and confirmed by targeted PORCN analysis. One patient had an atypical presentation with several malformations but only subtle skin changes and was diagnosed following trio exome‐sequencing analysis. Skin atrophy with fat herniations and telangiectasias were typical cutaneous findings. Limb malformations included oligodactyly (cleft foot), syndactyly, and polydactyly. Eye abnormalities included coloboma and microphthalmos. Facial dysmorphology was defined by asymmetry, thin upper lip, and malformed ears. One patient developed a giant cell bone tumor, which is a rare feature of FDH. Dental findings included enamel hypoplasia with vertical grooving and irregular crowns. Four PORCN variants were identified, including three not previously reported in the literature.We estimated a regional point prevalence in Western Denmark of 1.6 cases per million population (95% confidence intervals (CI): 0.7–3.7 per million) and a nationwide registry‐based point prevalence of 1.2 cases per million population (95% CI: 0.6–2.4 per million). Conclusions FDH is an extremely rare and complex multisystem disorder of variable presentation, which requires close multidisciplinary collaboration for diagnosis and patient care.