Comprehensive Phenotypic Analysis of 19 Individuals with Goltz Syndrome (Focal Dermal Hypoplasia). V. Sutton1, H. Herce2, T. R. Hunt3, A. L. Smith3, K. J. Motil4, A. F. Bree5, M. Fete6, R. W. Goltz7 1) Mol. & Human Genetics, Baylor College of Medicine, Houston, TX; 2) Department of Ophthalmology, Baylor College of Medicine, Houston, TX; 3) Department of Orthopedic Surgery, Baylor College of Medicine, Houston, TX; 4) Department of Pediatrics, Baylor College of Medicine, Houston, TX; 5) Dermatology Private Practice, Houston, TX; 6) National Foundation for Ectodermal Dysplasia, Fairview Heights, IL; 7) Department of Dermatology (Emeritus), University of California, San Diego, CA.

   Goltz syndrome is an X-linked dominant disorder caused by mutations in the gene PORCN. This pleiotropic disorder manifests in skin, skeleton and eyes. Information regarding the incidence of various phenotypic features in Goltz syndrome is limited and has come from small case reports and synthesis and summary of these individual reports. We present the largest clinical analysis of individuals with Goltz syndrome to date. Nineteen individuals from 18 families (one father-daughter pair) were studied. The average age was 12 years with a median age of 9 years and range of 1-55 years. Facial characteristics included: asymmetry (52%); hypoplastic alae nasi (87%); simple or crumpled ears, ear tags, ptosis, long columella, facial cleft and diastasis recti. All had skin atrophy that followed lines of Blashko and tended to be erythematous at birth and evolved over time into hypopigmented areas. There was a high frequency of sun sensitivity and fragility/bleeding with 47% having persistent crusted erosions. Telangectasias were seen in 84%. Papillomas were reported in 63%. The characteristic yellowbrown or pink lipomatous changes were seen in 68%. Patchy alopecia was seen in 79% and 42% had diffusely sparse scalp hair. Scanning electron microscopy revealed hair shaft abnormalities in 89% including narrow diameter, flattened shaft, pili torti and trichorrehexis nodosa; 16% had the uncommon finding of pili trianguli et canaliculi. Ridging and atrophy of the nails was seen in 84%. Major limb abnormalities were seen in 90% of individuals and included: Ectrodactyly (74%); syndactyly (84%); transverse limb deficiency (11%). Severe eye malformations were seen at rates higher than previously reported or summarized from the literature and included (percentages in eyes): right anophthalmia (5%); microphthalmia (42%); iris coloboma (47%); horioretinal coloboma (58%). Gynecological examination revealed bilateral labial hypoplasia in 88%, short perineum in all and vulvar papillomas in 18%. DNA mutation analysis of the PORCN gene did not identify any clear genotype-phenotype correlation. This is the largest analysis of phenotypic features in individuals with Goltz syndrome and provides for improved diagnosis, prognosis and management. In addition, the tissue repository for transformed lymphoblasts and fibroblasts will provide a resource to better understand the role of PORCN in WNT signaling and to screen and test potential new therapies for Goltz syndrome.

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