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113 SHORT COMMUNICATION Schöpf-Schulz-Passarge Syndrome: Previously Unreported WNT10A Genotype and Phenotypes in 9 Family Members Corinna E. ZIMMERMANN 1 , Muhidien SOUFI 2 , Volker RUPPERT 3 , Juergen R. SCHAEFER 2 and Helmut VON DOMARUS 1 Clinic of Oral and Maxillofacial Surgery, Breite Strasse 44–46, DE-23552 Lübeck, 2 Center for Undiagnosed and Rare Diseases (ZusE), and Department of Cardiology, University Hospital Giessen and Marburg, Marburg, Germany. E-mail: [email protected] 1 3 Accepted Sep 27, 2018; Epub ahead of print Sep 28, 2018 Schöpf-Schulz-Passarge Syndrome (1) (SSPS, ORPHA: 50944; OMIM: 224750; ICD-10: Q82.8) is a rare geno- dermatosis characterized by multiple cysts on the eyelids (apocrine hidrocystomas), palmo-plantar keratoderma, hypo- dontia, hypotrichosis, and nail dystrophy. While hypodontia can be diagnosed during childhood, the hallmark of SSPS (2, 3), hidrocystomas of the eyelids, develop at an advanced age, and, thus, SSPS may occasionally be underdiagnosed. The mode of inheritance and the underlying genetic funda- mentals have not been completely identified. Most of the 38 documented cases of SSPS are single or within 1 generation. Recently, mutations of the WNT family member (WN- T10A) gene have been linked to various ectodermal dyspla- sias (ED), e.g. odonto-onycho-dermal dysplasia (OODD) (4), including SSPS (3, 5). The WNT10A gene is expressed during multiple developmental processes including skin, tooth, hair, and nail embryogenesis. In adult tissues, WNT10A is involved in tooth and hair follicle mor­phogenesis by in- hibiting the ß-catenin degradation pathway. We recruited 14 family members from 2 generations for clinical and genetic analysis of symptoms of SSPS (Fig. S1 1 ). Patient examination included medical history and physical examination. Informed consent for DNA analysis, publication of data and photographs was obtained from all patients. Ethical aspects were in accordance with the principles outlined in the Declaration of Helsinki. Blood samples of all 14 participants were taken and analysed in the same manner. For molecular genetic analysis patients’ DNA was extracted and all coding exons of the WNT10A gene were amplified by PCR and Sanger sequenced in forward and reverse directions in all family members. Da- tabase searches for variant analysis were performed in the Human Gene Mutation Database (HGMD public), Exome Variant Server (EVS), Ensembl and ExAC. CASE REPORTS Patient 1. A 53-year-old man (IV.2 in the pedigree, Fig. 1A) pre- sented with multiple cystic lesions along the margins of his eyelids since his mid-40s. Histological examination revealed apocrine hidrocystoma. He reported severely callused skin of palms and soles with painful fissuring since his early 20s. His finger nails, and particularly his toe nails, were fragile and malformed. He denied excessive sweating. At age 17 years, he received partial dentures, because only 6 permanent tooth had developed. His primary den- tition had been normal. No permanent teeth had been removed. From the same age onwards, he noticed decreased growth of hair. Three years before presentation, a basal cell carcinoma of the right https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3055 1 Fig. 1. Patients 1 (IV.2) (A), 2 (IV.3) (B) and 3 (IV.7) (C) with numerous (recurrent) 1–2 mm clear or bluish cystic lesions of translucent or milky opacity bilaterally on the upper and lower eyelid margins. cheek had been removed. Genetic analysis identified 2 heterozy- gous nonsense mutations in exon 2 (c.321C>A;p.Cys107*) and exon 3 (c.742C>T;p.Arg248*) of the WNT10A gene (Fig. S2 1 ). Patient 2. The 51-year-old sister (IV.3) of patient 1 showed similar symptoms including eyelid cysts (Fig. 1B), keratoderma of the palms and soles, and oligodontia with only 8 permanent teeth pre- sent. For the past 1.5 years her nails had become dystrophic with hypoplasia, splitting, longitudinal furrows, and ridging. Her scalp hair was dry; she had sparse eyebrows and no hair on the legs and axillae. She reported not sweating at all and having xerostomia. Ge- netic analysis identified the same nonsense mutations as in patient 1. Patient 3. The 46-year-old sister (IV.7) of patient 1, reported cal- lused skin of the palms and soles with painful fissures, agenesis of 3 permanent teeth, and recurrence of previously removed eyelid cysts (Fig. 1C). Genetic analysis identified a nonsense mutation of only 1 allele (p.Arg248*). Patient 4. The 25-year-old daughter (V.3) of patient 1 exhibited no eyelid cysts, but mild keratoderma, nail dystrophy, and agenesis of 5 permanent teeth. She reported that her scalp hair never became greasy. Genetic analysis identified the same nonsense mutation as in patient 3. Patient 5. The 8-year-old daughter (V.7) of patient 3 had very dry, slowly growing scalp hair and agenesis of 5 permanent teeth. Ge- netic analysis identified the same nonsense mutation as in patient 3 (for phenotypes see Fig. S3 1 ). Four further family members were heterozygous carriers of one of the 2 mono-allelic nonsense mutations, but showed no features of SSPS. In the remaining 5 family members no mutations of the WN- T10A gene were detected (wild type) and no symptoms were noted. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3055 Acta Derm Venereol 2019; 99: 113–114