Acta Dermato-Venereologica 99-13CompleteContent | Page 32

1307 SHORT COMMUNICATION Oculodentodigital Dysplasia Diagnosed from Severe Hypotrichosis Tomoki TAKI 1 , Takuya TAKEICHI 1 , Kazumitsu SUGIURA 2 and Masashi AKIYAMA 1 * Department of Dermatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, and Department of Dermatology, Fujita Health University School of Medicine, Toyoake, Aichi, Japan. *E-mail: [email protected] 1 2 Accepted Aug 6, 2019; E-published Aug 6, 2019 Oculodentodigital dysplasia (ODDD, OMIM#164200) is a rare, mostly autosomal dominant, congenital disorder with variable phenotypes. ODDD presents as craniofacial abnormalities, limb dysmorphisms, microdentia, and neurological and ocular abnormalities. ODDD is caused by a heterozygous mutation in GJA1 (OMIM#121014), which encodes the gap junction protein connexin 43 (Cx43). We report here a 2-year-old boy with ODDD whose main symptom at his initial visit was severe hypotrichosis. CASE REPORT The proband is a 2-year-old Japanese boy who had presented with congenital alopecia. He showed severe hypotrichosis and low-set ears (Fig. 1a, b). Bilateral syndactyly of the 4 th and 5 th fingers was detected at birth (surgically repaired in infancy) and clinodactyly of the 5 th fingers was also detected (syndactyly type III, OMIM#186100) (Fig. 1c, d). He had no craniofacial, ocular or neurological abnormalities, nor hypohidrosis, and a head X-ray was normal (Fig. 1e). He was born to non-consanguineous parents with no family history of any similar disorder. Ethical approval was obtained and all research was performed in accordance with the principles of the Declaration of Helsinki. Using genomic DNA as a template, genomic sequencing of GJA1 was performed as reported previously (1). A mutation search revealed a previously reported heterozygous missense mutation in GJA1, c.412G>A (p.Gly138Ser) (Fig. 1f). Neither of his parents had any mutation in GJA1. This suggested that the mutation was de novo. Scanning electron microscopy revealed weathering in the cuticle layer of the patient’s scalp hair (Fig. 1g), but not in the cuticle layer of age- matched control samples (Fig. 1h). Neither monilethrix nor hair nodules/beads were seen in the patient. DISCUSSION As a cause of ODDD, 3 mutations have been repor- ted in the identical glycine residue at position 138: p.Gly138Ser, p.Gly138Arg and p.Gly138Asp. This suggests that the glycine residue in the cytoplasmic loop plays an important role in the function of Cx43. In mouse models, 30% of p.Gly138Arg mutant mice are born with sparse hair, and the phenotype becomes more apparent in adulthood (2). In another study, ap- proximately 20% of mice expressing p.Gly60Ser mutant ｍ Fig. 1. Clinical features of the present patient. (a, b) The patient shows hypotrichosis of the scalp and low-set ears. (c, d) Bilateral syndactyly of the 4 th and 5 th fingers was surgically repaired in infancy, but clinodactyly of the 5 th fingers remained. (e) No remarkable abnormalities are seen in the head X-ray. (f) Identification of the heterozygous missense mutation c.412G>A (p.Gly138Ser) in the GJA1 gene of the patient. The position of the mutation is indicated by the arrow. (g) Scanning electron microscopy reveals weathering (arrowheads) in the cuticle layer of the scalp hair, but not in (h) the cuticle layer of an age-matched control. Cx43 exhibited apparently lower hair density in the neck region. A histological comparison of the overall hair fol- licle density between p.Gly60Ser mutant mice and WT mice revealed no significant differences. However, after epilation or depilation, the mutant mouse hair was found This is an open access article under the CC BY-NC license. www.medicaljournals.se/acta Journal Compilation © 2019 Acta Dermato-Venereologica. ｍ doi: 10.2340/00015555-3277 Acta Derm Venereol 2019; 99: 1307–1308