Paediatric disorders - additional genes

Gene: CACHD1

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (three unrelated cases and functional studies) for the promotion of this gene to green rating on the next GMS update.

Created: 7 Jan 2025, 10:23 p.m. | Last Modified: 7 Jan 2025, 10:23 p.m.

Panel Version: 6.6

PMID:38158856 reported six affected individuals from four unrelated families with biallelic (either homozygous or compound heterozygous) CACHD1 variants (3 splice, 2 frameshift and 1 nonsense variant).

Excluding the two fetal cases from the fourth family, all others were affected by syndromic neurodevelopmental abnormalities, multiple organ systems featuring global impairment of psychomotor development, dysmorphic facial features, genitourinary abnormalities, oculo-auricular and congenital malformation. Cognitive impairment was reported to be mild in three cases from three different families, while the fourth case had no cognitive impairment. Psychomotor delay was reported in two unrelated cases and seizure was reported in one.

Functional evidence from human stem cell-derived neural models and zebrafish mutants are also available in support of the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype.
Sources: Literature

Created: 7 Jan 2025, 10:21 p.m. | Last Modified: 18 Jul 2025, 1:52 p.m.

Panel Version: 7.1

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
syndromic complex neurodevelopmental disorder, MONDO:0800439

Publications

• 38158856