Mexican patient with Ellis‐van Creveld syndrome and cleft palate: Importance of functional hemizygosity and phenotype expansion

• Published in: Molecular genetics & genomic medicine Vol. 12; no. 5; pp. e2451 - n/a
• Main Authors: León‐Madero, Luis Felipe, Fregoso‐Ron, Cesar Humberto, De León‐Carbajal, Juan Carlos, Valdés‐Miranda, Juan Manuel
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.05.2024; John Wiley and Sons Inc; Wiley
• Subjects: Amino acids; Birth defects; Cardiovascular disease; Case reports; Chromosome 4; Cleft lip/palate; cleft palate; Cleft Palate - genetics; Cleft Palate - pathology; Clinical Report; Clinical Reports; Congenital diseases; Ellis-van Creveld syndrome; Ellis-Van Creveld Syndrome - genetics; Ellis-Van Creveld Syndrome - pathology; EVC2; Female; Fetuses; Fingers & toes; functional hemizygosity; Genes; Genotype & phenotype; Genotypes; Heart; Hemizygosity; Humans; Informed consent; Intercellular Signaling Peptides and Proteins; Male; Mexico; Parents & parenting; Patients; Phenotype; Phenotypes; Proteins; Teeth; Ultrasonic imaging; Mexico; EVC2; cleft palate; Ellis‐van Creveld syndrome; functional hemizygosity
• ISSN: 2324-9269; 2324-9269
• DOI: 10.1002/mgg3.2451

Background Ellis‐van Creveld syndrome (EvCS) is a chondroectodermal dysplasia caused by germline pathogenic variants in ciliary complex subunit 1 and 2 genes (EVC, EVC2) on chromosome 4p16.2. This disease has a broad phenotype, and there are few described phenotype–genotype correlations. Methods Ethical Compliance: Written informed consent was obtained from the parents. Here, we report a genetically confirmed Mexican patient with EvCS having two inherited pathogenic variants in trans in EVC2: c.[1195C>T];[2161delC]. Results This patient allowed a genotypic–phenotypic comparison with another Mexican subject who presented a more attenuated phenotype; furthermore, our patient also presented cleft palate, a rarely reported feature. Conclusion Our case shows the importance of comparing functional hemizygosity between patient's phenotypes when they share a variant, and our case also supports the association of alterations in the palate as part of the EvCS phenotype. We report a genetically confirmed Mexican patient with Ellis‐van Creveld syndrome (EvCS) having two inherited pathogenic variants in trans in EVC2: c.[1195C>T];[2161delC]. This patient allowed a genotypic–phenotypic comparison with another Mexican patient who presented a more attenuated phenotype; furthermore, our patient also presented cleft palate, so our case also supports the association of alterations in the palate as part of the EvCS phenotype.