DISEASE CARD

Disease group FOCAL DERMAL HYPOPLASIA
DISEASE NAME FOCAL DERMAL HYPOPLASIA
Synonymous Goltz Syndrome
Estimated prevalence -
OMIM 305600
Inheritance X-linked Dominant
Gene (s) PORCN (300651)

Definition

Focal Dermal hypoplasia (FDH) is a rare X-linked ecto-mesodermal disorder. Also known as Goltz syndrome, FDH presents with characteristic linear streaks of hypoplastic dermis and variable abnormalities of bone, nails, hair, limbs, teeth and eyes. The molecular basis of FDH involves mutations in the PORCN gene, which encodes an enzyme that allows membrane targeting and secretion of several Wnt proteins critical for normal tissue development. 90% of affected individuals are female and the 10% of male cases present with clinical variability due to somatic mosaicism.

Clinical Description

Distinctive cutaneous features consist of linear streaks of hypo- or hyper-pigmented dermal atrophy, often occurring along Blaschko's lines, with areas of subcutaneous fat herniation associated with the focal lack of dermis. Dystrophic nails, sparse wiry hair and a variety of dental and ocular abnormalities are also features commonly observed in affected individuals. Digital deformities such as syndactyly, ectrodactyly or brachydactyly are frequently seen and many affected individuals develop striated areas of reduced bone density which is visible on X-rays of long bones (osteopathia striata). Significant clinical variability exists depending on the degree of Lyonization and somatic mosaicism.

Pathogenesis

In 2007, two groups (Wang et al. and Grzeschik et a.l reported mutations in the PORCN gene as the molecular basis of FDH. PORCN (human porcupine locus MG61/PORC) is a member of the porcupine (porc) gene family and is located on chromosome Xp11.23. The gene is thought to encode an O-acyltransferase that catalyses cysteine N-palmitoylation and serine O-acylation in the endoplasmic reticulum which allows membrane targeting and secretion of several Wnt proteins that have key roles in embryonic tissue development. To date, 24 different mutations in PORCN have been reported. These comprise six frameshifts, five microdeletions, six nonsense mutations, four small in-frame deletions/insertions, two missense mutations and one splice site mutation.

Diagnosis

Diagnosis is usually made by assessment of the clinical features either at, or soon after birth. In those individuals who have milder phenotypic features, the diagnosis becomes evident when hair, teeth ornails fail to develop normally. If a PORCN gene mutation is identified, this will help confirm the diagnosis. No other diagnostic tests are available at present.

Treatment

Management depends on the clinical severity of each affected individual. Those with milder phenotypes affecting the skin may only require topical emollients. However, those with extensive developmental systemic abnormalities will require surgical procedures to correct limb, teeth, eye and ear defects. Bony tumours including osteoclastomas have been reported in several cases and, though notmalignant, can be locally invasive and may result in pathological fractures. Dental treatment is extremely important for these individuals as many require successive dentures as a child with addition of dental implants and bridges later in adult life.