Scalp-Ear-Nipple syndrome: first report of a Potassium channel tetramerization domain-containing 1 in-frame insertion and review of the literature

• Published in: Clinical dysmorphology Vol. 30; no. 4; p. 167
• Main Authors: Butler, Kameryn M, Bahrambeigi, Vahid, Merrihew, Allie, Friez, Michael J, Cathey, Sara S
• Format: Journal Article
• Language: English
• Published: England 01.10.2021
• Subjects: Abnormalities, Multiple; Child; Co-Repressor Proteins - metabolism; Ear, External - abnormalities; Ear, External - metabolism; Ectodermal Dysplasia - diagnosis; Ectodermal Dysplasia - genetics; Humans; Hypospadias; Male; Muscle Hypotonia; Nipples - abnormalities; Potassium Channels - genetics; Scalp - abnormalities; Scalp - metabolism
• ISSN: 1473-5717
• DOI: 10.1097/MCD.0000000000000387

Pathogenic missense variants in the potassium channel tetramerization domain-containing 1 (KCTD1) gene are associated with autosomal dominant Scalp-Ear-Nipple syndrome (SENS), a type of ectodermal dysplasia characterized by aplasia cutis congenita of the scalp, hairless posterior scalp nodules, absent or rudimentary nipples, breast aplasia and external ear anomalies. We report a child with clinical features of an ectodermal dysplasia, including sparse hair, dysmorphic facial features, absent nipples, 2-3 toe syndactyly, mild atopic dermatitis and small cupped ears with overfolded helices. We also review the published cases of SENS with molecularly confirmed KCTD1 variants. Using whole-exome sequencing, we identified a novel, de novo in-frame insertion in the broad-complex, tramtrack and bric-a-brac (BTB) domain of the KCTD1 gene. By comparing to the previously reported patients, we found that our patient's clinical features and molecular variant are consistent with a diagnosis of SENS. This is only the 13th KCTD1 variant described and the first report of an in-frame insertion causing clinical features, expanding the mutational spectrum of KCTD1 and SENS.