A recurrent KCNK4 variant in a dominant pedigree with hypertrichosis and gingival fibromatosis syndrome: Variable phenotypic expressivity and insights on patients' dental management

• Published in: American journal of medical genetics. Part A Vol. 194; no. 1; pp. 39 - 45
• Main Authors: Elhossini, Rasha M., Sayed, Inas M., Hellal, Usama Saad, Mahmoud, Sarah A. M., Aglan, Mona S., Hassib, Nehal F., Abdel‐Hamid, Mohamed S.
• Format: Journal Article
• Language: English
• Published: Hoboken, USA John Wiley & Sons, Inc 01.01.2024; Wiley Subscription Services, Inc
• Subjects: Cell proliferation; Dental Care - adverse effects; Epilepsy; Fibromatosis, Gingival - diagnosis; Fibromatosis, Gingival - genetics; Genotype & phenotype; Genotypes; Gingiva; Gingival fibromatosis; Gingival Overgrowth - complications; Humans; Hyperpolarization; Hypertrichosis; Hypertrichosis - genetics; Intellectual Disability - complications; Intellectual Disability - genetics; intellectual/developmental delay; KCNK4; Male; Mastication; Nervous system; Pedigree; Periodontal ligament; Phenotype; Phenotypes; Potassium Channels - genetics; Syndrome; epilepsy; hypertrichosis; intellectual/developmental delay; gingival fibromatosis; KCNK4
• ISSN: 1552-4825; 1552-4833; 1552-4833
• DOI: 10.1002/ajmg.a.63415

Abnormal hyperpolarization of the KCNK4 gene, expressed in the nervous system, brain, and periodontal ligament fibroblasts, leads to impaired neurotransmitter sensitivity, cardiac arrhythmias, and endocrine dysfunction, as well as, progressive cell proliferation. De novo gain of function variants in the KCNK4 gene were reported to cause a recognizable syndrome characterized by facial dysmorphism, hypertrichosis, epilepsy, intellectual/developmental delay, and gingival overgrowth (FHEIG, OMIM# 618381). FHEIG is extremely rare with only three reported cases in the literature. Herein, we describe the first inherited KCNK4 variant (c.730G>C, p.Ala244Pro) in an Egyptian boy and his mother. Variable phenotypic expressivity was noted as the patient presented with the full‐blown picture of the syndrome while the mother presented only with hypertrichosis and gingival overgrowth without any neurological manifestations. The c.730G>C (p.Ala244Pro) variant was described before in a single patient and when comparing the phenotype with our patient, a phenotype–genotype correlation seems likely. Atrial fibrillation and joint laxity are new associated findings noted in our patient extending the clinical phenotype of the syndrome. Dental management was offered to the affected boy and a dramatic improvement was noted as the patient regained his smile, restored the mastication function, and resumed his psychological stability.