Case Report: Autosomal Recessive Palmoplantar Keratoderma with Additional Bilateral Hearing Loss due to a Pathogenic Frameshift Deletion in FAM83G

Mónica Mora-Gómez^1,2,3Marta Feito⁴Natalia Gallego-Zazo^1,2,3Rocío Maseda-Pedrero⁴Tristán G Sobral-Costas⁴Lucía Miranda-Alcaraz^1,2,3Valeria Vásquez-Amell^1,2,3Manuel Rodríguez-Canó^1,2,3Alejandro Parra^1,2,3Mario Cazalla^1,2,3Pedro Arias^1,2,3Cristina Silván^1,2,3Juan A Jiménez-Estrada^1,2,3Víctor L Ruiz-Pérez^1,2,3,5Julián Nevado^1,2,3Pablo Lapunzina^1,2,3Jair Tenorio^1,2,3*

• ¹Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
• ²Instituto de Genética Médica y Molecular Hospital Universitario La Paz, Madrid, Spain
• ³ITHACA European Reference Network, Brussels, Belgium
• ⁴Hospital Universitario la Paz Servicio de Dermatología, Madrid, Spain
• ⁵Instituto de Investigaciones Biomedicas Sols-Morreale, Madrid, Spain

Palmoplantar keratoderma (PPK) comprises a group of genodermatosis disorders phenotypically characterized by the isolated thickening of the skin of palms and soles. Syndromic forms can also include other phenotypic features in addition to those affecting the skin. Genetics plays a major role in the etiology and classification of PPK, particularly in syndromic cases, although the genetic mechanisms underlying some cases remain largely unknown. Here, we present a patient from a consanguineous family in which a homozygous variant was identified through whole exome sequencing in the FAM83G gene. The identified variant consists of the deletion of one nucleotide and a subsequent frameshift, leading to an early stop codon and a potentially truncated protein. FAM83G gene has been associated with PPK relatively recently, and therefore, the phenotype arising from mutations in this gene needs further refinement based on the small number of reported cases. The phenotype of the patient included keratoderma both in hands and feet and bilateral hearing loss, without hair or tooth abnormalities. This patient adds new clinical features and molecular supporting information for this novel genodermatosis syndrome with an apparently autosomal recessive pattern of inheritance. This entity caused by FAM83G pathogenic variants can be named as FAM83G-associated palmoplantar keratoderma.