HELIX Syndrome, a Claudinopathy with Relevant Dermatological Manifestations: Report of Two New Cases.
María Carmen Martínez-RomeroMaría Encarnación Hernández-ContrerasJuan Antonio Bafalliu-VidalMaría Barreda-SánchezTeresa Martínez-MenchónVirginia Cabello-ChavesEncarna Guillén-NavarroPublished in: Genes (2024)
HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [ CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.
Keyphrases
- copy number
- genome wide
- emergency department
- end stage renal disease
- case report
- ejection fraction
- genome wide identification
- ionic liquid
- dna methylation
- dna binding
- single cell
- newly diagnosed
- chronic kidney disease
- protein protein
- pulmonary embolism
- prognostic factors
- peritoneal dialysis
- binding protein
- depressive symptoms
- small molecule
- body mass index
- risk assessment
- gene expression
- patient reported outcomes
- soft tissue
- physical activity
- human immunodeficiency virus
- mass spectrometry
- patient reported
- genome wide analysis