Acta Dermato-Venerelogica Issue No 7, 2017 97-7CompleteContent | Page 22

853 SHORT COMMUNICATION Mosaic Focal Dermal Hypoplasia (Goltz Syndrome) in Two Female Patients Maella SEVERINO-FREIRE 1 , Aude MAZA 1 , Maria Paola LOMBARDI 2 , Emelie TOURNIER 3 , Nicolas CHASSAING 4,5 and Juliette MAZEREEUW-HAUTIER 1,4 Department of Dermatology, Toulouse University Hospital, 24 chemin de Pouvourville TSA, FR-31059 Toulouse cedex 9, France, 2 Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, The Netherlands, 3 Anatomo Pathology Department, IUC Oncopole, Paul Sabatier University, Toulouse, 4 U 1056 INSERM – FRE 3742 CNRS - Université Toulouse III ‘Différenciation Epithéliale et Autoimmunité Rhumatoïde’, Toulouse, and 5 Medical Genetics Department, CHU Purpan, Paul Sabatier University, Toulouse, France. E-mail: maella. [email protected] 1 Accepted Mar 15, 2017; Epub ahead of print Mar 15, 2017 Focal dermal hypoplasia (FDH) or Goltz syndrome is an ectodermal and mesodermal disorder characterized by abnormalities of various organs including the skin. Cutaneous anomalies include skin hypoplasia, hyper- or hypo-pigmented areas following the lines of Blaschko, nodular fat herniation and papillomas. Hair can be sparse and brittle. Nail findings include ridging, dysplasia or hypoplasia. Many other organs may be involved, the most common anomalies being skeletal anomalies (especially on the extremities), short stature, coloboma of the iris and retina (1–3). FDH is caused by mutations of the PORCN gene (Xp11.23) (4, 5) encoding a 461 amino acid 52-kDa protein involved in the secretion and signalling of WNT proteins, which plays a key role in embryonic tissue development (6). Approximately 250 individuals with FDH have been reported in the literature so far, either in small series (3–18 patients) (2) or in case reports (7). In 2016, 119 different mutations were registered in the PORCN mutation database (http://www. lovd.nl/PORCN). The majority of muta- tions are scattered throughout the entire coding sequence of the PORCN gene. Large deletions and splice site mutations were also reported (2). FDH is inherited as an X-linked dominant disorder, with females accounting for 90% of affected in- dividuals. Ninety-five percent of affected women have de novo mutations, whereas 5% inherit the mutation from their parents (the mother or, rarely, the father, is affected by post-zygotic mutation) (2, 8). In men, hemizygosity for a mutation in PORCN (9) is presumed to be lethal. However, males may survive in case of Klinefelter syn- drome (8) or mosaic forms (2). Postzygotic mutations of PORCN have occasionally been reported in females. We report here 2 novel cases of FDH mosaic in female patients. examination, she had linear hyperpigmented and atrophic lesions in a Blaschkoid distribution. Lesions were located on the right arm, right leg and left trunk and involved approximately 10% of the body surface. She also had syndactyly of 2–3 and 4–5 fingers of the left hand (Fig. 1). Histology performed on lesional skin showed some scattered apoptotic cells in the epidermis and pigment incontinence in the superficial dermis. After obtaining written consent, molecular analysis was performed by Sanger sequencing of the coding exons and exon-intron boundaries of the PORCN gene (NM_203475.2, variant D) and multiplex ligation- dependent probe amplification (MLPA) analysis. Both tests were performed on DNA extracted from peripheral blood leukocytes and did not reveal any mutation. Molecular analysis of PORCN was then performed on DNA extracted from saliva and revealed the mutation c.173_178delinsACT (p.Ala58_Gly60delinsAspTrp). This mutation has not been reported previously and was absent from the ExAc control population (10). The percentage of cells carrying the mutation seems low in saliva, but cannot be deter- mined precisely. This mutation is thought to be damaging as it is responsible for the deletion of 3 highly conserved amino acids. Case 2. A 16-year-old female with healthy, non-consanguineous parents presented since birth with skin lesion in a limited distri- bution (3% of body surface area). She had Blaschko linear hy- CASE REPORTS Case 1. A 21-year-old woman presented with skin lesions since birth. She had no medical history and her parents were not consanguineous. At Fig. 1. Case 1. (a, b) Linear hyperpigmented and atrophic lesions in a Blaschkoid distribution on the left trunk and right leg. (c) Syndactyly of 2–3 and 4–5 fingers of the left hand. This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2017 Acta Dermato-Venereologica. doi: 10.2340/00015555-2648 Acta Derm Venereol 2017; 97: 853–854