From Clinical Observation to Genetic Confirmation: Somatic Mosaic Mutations in RHOA on Ectodermal Dysplasia With Multi-System Involvement

Am J Med Genet A. 2024 Nov 20:e63934. doi: 10.1002/ajmg.a.63934. Online ahead of print.

Abstract

Ectodermal dysplasia with facial dysmorphism and acral, ocular, and brain anomalies (EDFAOB) is a rare neuroectodermal syndrome caused by somatic mosaic mutations in the RHOA gene. It presents with linear skin hypopigmentation, facial and limb asymmetry, dental and acral anomalies, and leukoencephalopathy, generally preserving intellectual and neurological functions. We report two cases of EDFAOB. Both cases initially presented with notable facial-body asymmetry, thin hair, dental issues, digital anomalies, and Blaschko's lines-aligned hypopigmentation. A 6-year-old girl exhibited esotropia, visual center atrophy, and bilateral white matter hyperintensities on MRI. A 10-year-old girl had unilateral hyperintense lesions in the left cerebral hemisphere on MRI. Both had normal neuromotor development without intellectual impairment. RHOA gene sequencing from hypopigmented skin biopsies revealed the c.139G > A (p.Glu47Lys) mutation, with allele fractions of 20% and 10%, respectively, absent in blood leukocytes and parental DNA. These cases highlight the clinical and genetic features of EDFAOB and underscore the importance of thorough clinical evaluation to guide precise genetic testing. The identification of mutations exclusively in affected tissues supports a postzygotic mosaic distribution, refining the diagnostic approach for this syndrome.

Keywords: RHOA; ectodermal dysplasia; hypopigmentation; neuroectodermal syndrome; somatic mosaicism.

Publication types

  • Case Reports