Acta Dermato-Venereologica 99-1CompleteContent | Page 31

SHORT COMMUNICATION A Case of Ankyloblepharon-ectodermal Defects-cleft Lip/Palate-syndrome with Choanal Atresia and Skin Erosions: Phenotypic Variability of TP63-related Disorders Luana NICULESCU 1,2 , Matias WAGNER 3,4 , Dominik S. WESTPHAL 4,5 , Marcus FISCHER 6 , Walter MIHATSCH 7 , Anke PROTHMANN 8 , Thomas RUZICKA 1 , Andreas WOLLENBERG 1 , Hans WOLFF 1 , Heinrich SCHMIDT 9 and Kathrin A. GIEHL 1,2 * 1 Department of Dermatology and Allergy, 2 Center for Rare and Genetic Skin Diseases, Department of Dermatology, 6 Department of Pediatric Cardiology and Pediatric Intensive Care Medicine, Ludwig Maximilian University, Frauenlobstrasse 9–11, DE-80337 Munich, 3 Institute of Neurogenomics and 4 Institute of Human Genetics, Helmholtz Zentrum Munich, Neuherberg, 5 Institute of Human Genetics, Technical University Munich, Munich, 7 Department of Pediatrics, HELIOS Klinikum Pforzheim, Pforzheim, 8 Department of Pediatrics, Harlaching, Munich Municipal Hospitals, Munich, and 9 Department of Pediatrics and Medical Genetics, Dr. von Hauner Children’s Hospital, Ludwig Maximilian University, Munich, Germany. E-mail: [email protected] Accepted Jun 26, 2018; Epub ahead of print Jun 29, 2018 Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome is an autosomal dominant disease. AEC was first described by Rapp & Hodgkin in 1968 in a family in which the patients presented the same clinical traits (1). Until now, differentiation between AEC and Rapp- Hodgkin syndrome (RHS) has been made by the presence of ankyloblepharon and midfacial hypoplasia, respectively (2, 3). However, as has been stated previously, differen- tiation between AEC and RHS should be abandoned in favour of a more inclusive term (4). TP63 encodes the p63 protein, which is essential for the maintenance of epidermal stem cells. Furthermore, p63 takes part in the morphogenesis and maintenance of the epidermis. It regulates the proliferation and differentia- tion of keratinocytes. Mutations in TP63 also cause other syndromes, such as acro-dermato-ungual-lacrimal-tooth syndrome (ADULT), ectrodactyly–ectodermal dyspla- sia–cleft syndrome (EEC syndrome), split-hand/split-foot malformation type 4 (SFHM4), limb-mammary syndrome (LMS) and isolated cleft lip/cleft palate (CL/P) (5). CASE REPORT 111 A newborn girl was referred to the Center for Rare and Genetic Skin Diseases from the Department of Pediatrics of Harlaching, Municipal Hospital, Munich, Germany . She was the 2 nd child of healthy, non-consanguineous parents of Caucasian origin, and was born at 41+1 weeks by vaginal delivery. At birth her weight was 3,530 g (45 th centile), length 54 cm (79 th centile) and head circumference 37 cm (91 th centile). At birth, she presented with generalized erythema and widespread superficial skin erosions on the lumbosacral region (Fig. 1a). The girl had facial deformity, including midfacial hypoplasia, bilateral ectropion, small nasal bridge, long philtrum, microstomia and nail hypoplasia. Despite the striking clinical findings, she was in good general health with no raised inflammatory markers. After 10 days she developed difficulty suckling. A nasal-gastric catheter could not be passed through the nostrils, therefore magnetic resonance imaging (MRI) was performed. This confirmed the presence of bilateral bony choanal atresia. Several surgical interventions were perfor- med to correct the defect. Her renal function was normal, but a renal pelvis dilatation was identified, which could lead to urinary dysfunction or even obstruction. The lumbosacral erosions healed, but new erosions with crusts appeared on the fronto-parietal scalp (Fig. 1b). By 3 months the girl’ growth was normal; length 57 cm (45 th centile) and weight 5,180 g (29 th centile). At the age of 6 months the erosions on her scalp improved and white, wiry hair was observed. Trichoscopy revealed a lack of Fig. 1. (a) Generalized erythema of the skin and multiple erosions on the lumbosacral region. (b) Erosions of the scalp. (c) Erosions of the scalp with sparse, white wiry hair. (d) Dark pigmented teeth. Permission to publish these photographs are given by the patient’s parents. pigment. At the age of 11 months new erosions appeared on the scalp as well as diffuse alopecia (Fig. 1c). The fingernails and toe­ nails had developed from hypoplastic (Fig. S1a, b 1 ) to dystrophic (Fig. S1c 1 ), and the appearance of dark pigmented teeth was noted (Fig. 1d). During follow-ups bacterial swabs were taken from the scalp and showed massive colonization with Staphylococcus aureus, which was treated with topical antibiotics (fusidic acid), in combination with betamethasone, and antiseptic measures with polyhexanide. To summarize the clinical findings: the young patient presented at birth and at 1 month with skin erosions on the scalp, nail dyspla- sia, teeth anomalies, genitourinary deformities and choanal atresia (Table SI 1 ). As in the first weeks, many of the clinical findings were not yet present, and because they could not be attributed to a specific syndrome, single exome sequencing was performed. The previously published heterozygous missense variant c.1790T>C, p.(lle597Thr) was identified in the TP63 gene, which has been described previously in a patient with AEC syndrome (5). The variant was not listed in 120,000 control alleles of the Exome Aggregation Consortium (ExAC)-Browser and it was predicted to change a conserved amino acid. The de novo status was confirmed by carrier testing of the unaffected parents. The variant could not be identified in blood DNA from the parents using Sanger sequencing. https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-2997 1 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-2997 Acta Derm Venereol 2019; 99: 111–112