Paediatric disorders - additional genes

Gene: KCNJ8

Green List (high evidence)

Four unrelated patients with Cantu syndrome and de novo missense KCNJ8 variants have been reported in the literature. Cantu syndrome is also, more frequently, associated with monoallelic ABCC9 variants. Recurrent features, consistent with ABCC9-related Cantu syndrome include generalised hypertrichosis, coarse facial appearance/ facial dysmorphism, macrosomia, and Osteochondrodysplasia.

PMID 24176758: de novo KCNJ8 c.193G>A p.(Val65Met), identified by trio exome sequencing after exclusion of ABCC9 variants. Reported features included hypertrichosis, macrosomia, macrocephaly, coarse facies, cardiomegaly, hypertension, developmental delay and skeletal/vascular abnormalities.

PMID 24700710: de novo KCNJ8 c.526T>A p.(Cys176Ser), identified by targeted Sanger sequencing in an ABCC9-negative patient. Features included hypertrichosis, macrosomia, macrocephaly, coarse facies, cardiomegaly, patent ductus arteriosus, developmental delay and skeletal abnormalities. Functional studies demonstrated K-ATP-channel gain of function.

PMID 32215968: de novo KCNJ8 c.991G>A p.(Glu189Lys) identified in an ABCC9-negative Japanese patient with hypertrichosis, coarse facies, patent ductus arteriosus and delayed motor development. No skeletal features were noted.

PMID 35243770: de novo KCNJ8 c.994G>A p.(Glu332Lys), identified by trio exome sequencing in an infant with Cantu syndrome, presenting with hypertrichosis, macrocephaly, facial dysmorphism, cardiomegaly, and vascular and skeletal abnormalities. The authors compared features reported in the four KCNJ8-related Cantu patients reported to date with ACCC9-related Cantu disease and noted similar features, as expected (table 1).

KCNJ8 is not yet associated with the relevant phenotype in OMIM,but is cited in G2P with a strong association with monoallelic KCNJ8-related Cantu syndrome.
Sources: Literature

Created: 5 Nov 2026, 3:07 p.m. | Last Modified: 5 Nov 2026, 4:39 p.m.

Panel Version: 8.33

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
hypertrichotic osteochondrodysplasia Cantu type (MONDO:0009406)

Publications

• 24176758
• 24700710
• 33617015
• 35243770

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments