Acta Dermato-Venereologica 99-9CompleteContent | Page 23

SHORT COMMUNICATION 831 Palmoplantar Keratoderma and Woolly Hair Revealing Asymptomatic Arrhythmogenic Cardiomyopathy Liliana GUERRA 1 , Monia MAGLIOZZI 2# , Anwar BABAN 3# , Corrado DI MAMBRO 3 , Giovanni DI ZENZO 1 , Antonio NOVELLI 2 , May EL HACHEM 4 , Giovanna ZAMBRUNO 5 and Daniele CASTIGLIA 1 1 Laboratory of Molecular and Cell Biology, IDI-IRCCS, via dei Monti di Creta 104, IT-00167 Rome, 2 Medical Genetics Unit and Laboratory of Medical Genetics, 3 Pediatric Cardiology and Cardiac Arrhythmia/Syncope Unit, Department of Pediatric Cardiology and Cardiac Surgery, 4 Dermatology Unit, and 5 Genetics and Rare Diseases Research Division, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy. E-mail: [email protected] # These authors equally contributed to the work Accepted May 9, 2019; E-published May 10, 2019 The association of woolly hair and palmoplantar kera­ toderma (PPK) has been found in 2 autosomal recessive syndromic disorders: Naxos diseases (OMIM 601214) and Carvajal syndrome (OMIM 605676), both also pre­ senting progressive arrhythmogenic cardiomyopathy. Naxos disease is characterized by the triad of diffuse PPK, woolly hair and right ventricular (RV) arrhythmo­ genic cardiomyopathy (AC) and is caused by homozy­ gous mutations in the plakoglobin gene (JUP) (1). Car­ vajal syndrome manifests with striated and fokal PPK, woolly hair and left-dominant dilated cardiomyopathy and is due to recessive mutations in the desmoplakin gene (DSP) (2). Few patients with these syndromes have been described (3–6). AC due to autosomal dominant DSP mutations, with (OMIM: 615821) or without (OMIM 607450) hypo/oligodontia, may be also associated with PPK and woolly hair (5–7). CASE REPORT A 5-year-old female child first presented for hypotrichosis to the Rare Skin Disease outpatient clinic of IDI-IRCCS. She was born at term from healthy non-consanguineous parents. Physical examination revealed light-coloured woolly, sparse and fragile hair, which had never required cutting (Fig. 1a), focal plantar hyperkeratosis localized at pressure areas (Fig. 1b) and minimal striated hyperkeratosis of the palmar aspect of the first 3 digits of the hand (Fig. 1c). The patient also had dry skin and mild keratosis pilaris of the arms and thighs. Her parents reported that hair abnormalities had been present since birth, while plantar keratoderma manifested approximately at 1 year of age, followed by palmar lesions. Her nails and teeth were normal. The patient was otherwise in good general health. Histological examination of a plantar hyperkeratosis biopsy revealed massive hyperkeratosis, parakeratosis and acanthosis of the epidermis with acantholytic clefts between neighbouring keratinocytes and widened inter­ cellular spaces in the suprabasal cell layers (Fig. 1d). Although histopathological findings were highly suggestive for involvement of a desmosomal protein component, molecular testing for the corresponding genes was not available at that time in Italy. The patient was therefore discharged with a diagnosis of epidermolytic PPK with woolly hair, and the recommendation to have a cardio­ logical evaluation and follow-up in Sicily where the family lived. An electrocardiogram (ECG) and echocardiogram did not reveal any abnormality. Five years later (age 10 years), the family was contacted again as in the meantime molecular diagnosis became available at Bambino Gesù Children’s Hospital. Following written informed consent, genomic DNA was extracted from EDTA-blood and submitted to next-generation sequencing of a gene panel as­ sociated with cardiomyopathies (DES, DSC2, DGS2, DSP, JUP, Fig. 1. Clinical and histopathological findings. (a) Woolly and sparse hair. (b, arrows) Focal plantar hyperkeratosis localized at pressure areas. (c, arrows) Minimal striated hyperkeratosis of the palmar aspect of the first 3 digits of the hand. (d) Hyperkeratosis with focal parakeratosis and suprabasal epidermal acantholysis in the haematoxylin-eosin staining. Bar: 50 μm. LAMP2, PKP2). The analysis revealed 2 heterozygous truncating mutations in DSP (NM_004415): c.4788delA (p.Glu1597Serfs*5) and c.6091_6092delTT (p.Leu2031Glyfs*29) affecting exon 23 and 24, respectively. The former mutation was inherited from the father and the latter from the mother, as confirmed by Sanger sequencing (Fig. S1 1 ). The patient was then referred to the Car­ diology and Arrhythmology Unit. Cardiological examination findings are presented in Table SI 1 and Fig. S2 1 . After a complete cardiac work-up, Carvajal syndrome was diagnosed on the basis of combined phenotype of woolly hair, striate PPK, left-dominant arrhythmogenic cardiomyopathy and molecular analysis findings. Therefore, the patient received an implantable subcutaneous cardioverter-defibrillator (ICD) and started anti-congestive heart failure treatment with angiotensin-converting enzyme inhibitors, beta-blockers and diuretics. At follow-up visits, the patient was in a fair general condition. https://www.medicaljournals.se/acta/content/abstract/10.2340/00015555-3216 1 This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. doi: 10.2340/00015555-3216 Acta Derm Venereol 2019; 99: 831–832