1- Medical Genetics Department, Hospital de Dona Estefânia, Área da Mulher, Criança e Adolescente, Centro Hospitalar Universitário de Lisboa Central, EPE
2- Medical Genetics Department, Hospital de Santa Maria, Centro Hospitalar de Lisboa Norte, EPE
3- Centro de Genética Preditiva e Preventiva, Instituto de Biologia Molecular
- 23ª Reunião da Sociedade Portuguesa de Genética Humana, 14-16 de Novembro de 2019
Case Report: Here we report a case of a 20-month-old female referred to our clinic by prenatal polyhydramnios and dysmorphic facial features. At clinical observation, coarse facial features, low frontal hairline and generalized hypertrichosis predominantly on both arms, were noticed. Cardiac evaluation showed dysplastic aortic valve. A possible diagnosis of lysosomal storage disease was suspected but an extensive normal metabolic evaluation excluded this hypothesis. Clinical reevaluation at 8 yrs, showed short stature (<5th centile), joint hyperlaxity, pectus carinatum, astigmatism and hyperopia, as well as learning difficulties. With time the dysmorphic facial features became more evident, resembling Cantú syndrome. Sanger sequencing of ABCC9 gene was normal. At 14 yrs, cardiac evaluation revealed hypertrophic cardiomyopathy and pulmonary hypertension. By that age, she developed panhypopituitarism (growth hormone deficit, hypogonadotropic hypogonadism, hypothyroidism, hypocortisolism) and relapsing polychondritis. Clinical exome sequencing was performed which did not reveal pathogenic variants, however targeted reanalysis of KCNJ8 gene showed a novel variant (p.E331K) de novo predicted to be pathogenic.
Discussion: Cantú syndrome is a rare autosomal dominant disorder characterized by hypertrichosis, a distinctive facial appearance, heart defects and several other abnormalities caused by mutations in ABCC9 and KCNJ8 genes. More than 30 patients with pathogenic variants on ABCC9 have been previously reported. Pathogenic variants in KCNJ8 gene, which encodes a member of the inward rectifier potassium channel family, were only previously reported in two other patients. Both of them shared phenotypical characteristics with our patient like hypertrichosis, coarse facies, developmental delay. Endocrinological abnormalities have not been previously reported.
Conclusion: To our knowledge, this is the third case report of Cantú syndrome associated to KCNJ8 gene, reinforcing its contribution to the phenotype. We emphasize the importance of the clinical exome sequencing in the diagnosis of rare diseases as well as the importance of a close collaboration between clinical and laboratory geneticists.
Palavras Chave: Cantú Syndrome