Focal dermal hypoplasia (FDH) is an uncommon genetic disorder characterized by distinctive skin abnormalities and a wide variety of defects that affect the eyes; teeth; and skeletal, urinary, gastrointestinal, cardiovascular, and central nervous systems. It is usually, but not always, X-linked dominant (lethal in males except if male is mosaic). About 90% of affected individuals are female. Ninety-five percent are new mutations. The mnemonic FOCAL can be used to remember some of the key features of this syndrome: female sex; osteopathia striata; coloboma; absent ectodermis-, mesodermis-, and neurodermis-derived elements; and lobster claw deformity. Focal dermal hypoplasia is also known as Goltz syndrome or Goltz-Gorlin syndrome. [1, 2, 3, 4, 5]
These eponyms should not to be confused with Gorlin syndrome or Gorlin-Goltz syndrome, which is the nevoid basal cell carcinoma syndrome. Focal dermal hypoplasia is identified as entry #305600 in the Online Mendelian Inheritance of Man database.
Affected individuals are often recognized at birth or occasionally prenatally, but cases involving a minor expression of the syndrome may be diagnosed later in life.
The focal dermal hypoplasia (FDH) genetic defect has been associated with at least 80 different mutations in the PORCN gene on the X chromosome. In 2007, Wang et al identified a region of 11p11.23 that encompassed PORCN gene.  Subsequently, nonsense, frameshift, aberrant splicing, and missense mutations have been identified in patients with focal dermal hypoplasia.  No genotype–phenotype correlation has been found.
The biochemical functions of the human PORCN gene still are not completely characterized; However, a lot is known about PORCN signaling in the mouse and in humans. This gene provides instructions for making a protein that is responsible for modifying other proteins, including Wnt proteins. Wnt signaling is critical for normal embryonic development of the skin, bones, and other structures. Since Wnt signaling proteins cannot be released without the PORCN protein and Wnt signaling is important for normal embryonic development, the defects found in this disorder are related to lack of Wnt signaling. [8, 9, 10, 11]
The severity of defects in focal dermal hypoplasia are variable, and this variability is due to random X-chromosome inactivation (lyonization) within cells. In females, 1 of the 2 X chromosomes is randomly inactivated in every cell. The result is functional mosaicism of cells. Tissues in which cells select for the defective PORCN gene inactivated show anomalies. In the skin, these abnormalities follow the embryonic lines of Blaschko.
Approximately 10% cases occur in males; postzygotic somatic mosaicism accounts for the findings in these affected males. Postzygotic somatic mosaicism is also postulated for the sporadic female cases with negative family pedigree analysis.
Focal dermal hypoplasia (FDH) is an uncommon disorder.
Focal dermal hypoplasia is an uncommon but not rare disorder. Worldwide, 200-300 cases have been reported. The exact incidence and prevalence are unknown.
All races have been affected.
The syndrome occurs predominantly in females. It is usually X-linked dominant with male lethality in utero. A small number of male patients have been reported, mostly with postzygotic somatic mutations. Rarely, father-to-daughter transmission occurs. This may be explained by mutations occurring early enough in the development of a male embryo to affect the gonads.
Focal dermal hypoplasia is present at birth but may evolve thereafter and, in mildly affected individuals, may be recognized only later in life.
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