Focal dermal hypoplasia
Overview
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). 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. FDH is also known as Goltz syndrome or Goltz-Gorlin syndrome.
Causes
Studies indicate that FDH is usually caused by mutations of the PORCN gene, mapped to locus Xp11.23.14, 15, 16 PORCN, a member of the porcupine (PORC) gene family, encodes transmembrane endoplasmic reticulum proteins that target Wnt signaling proteins. Wnt proteins are key regulators of embryonic development. Even though biochemical functions of the human PORCN gene are not well characterized (and therefore Wnt-independent signaling may be involved in the phenotypic expression of FDH), current analysis implicates that defective/deficient Wnt signaling could affect cell fate or could result in failure of a progenitor cell line to expand.14, 15 Drosophila melanogaster porcupine and its mouse homologue PORCN gene encode transmembrane bound endoplasmic reticulum proteins needed for the secretion of Wnt (Wingless and INT-1) proteins. (In Drosophila melanogaster, the PORCN gene is involved in the processing of the wingless protein.) Investigators have detected embryonic mouse expression of PORCN in cartilage, primordia of long bones and digits, calvaria, the facial skeleton, molar tooth buds, the petrous part of the temporal bone, as well as affecting developing skin of the anterior body wall and limbs; and in the developing cerebral cortex and retina. These findings correlate with the developmental defects seen in persons with FDH. Dilated, rough endoplasmic reticulum containing granular material has been observed in FDH skin fibroblasts; a correlation to a Wnt protein, however, is yet to be determined.
Treatment
Medical Care Regular surveillance, with frequency increased as needed during and after adolescence, facilitates early detection of anomalies and timely preventative and/or corrective treatment planning. Medical management is targeted toward the various soft-tissue, dental,22 and skeletal anomalies, with the goal of achieving optimal functional and aesthetic results. Treatment with a flashlamp-pumped pulse dye laser may ameliorate the pruritic symptoms that sometimes are noted in affected skin, and it may improve the clinical appearance of the telangiectatic and erythematous skin lesions.23 Surgical Care Surgical management is targeted toward the various soft-tissue, dental, and skeletal anomalies, with the goal of achieving optimal functional and aesthetic results. Periorificial fibrovascular papillomas may continue to appear during adulthood; these papillomas require repeated surgical intervention.