Paediatric disorders - additional genes

Gene: WDHD1

Green List (high evidence)

Comment on list classification: There are 14 unrelated families reported with biallelic WDHD1 variants and presenting with microcephalic primordial dwarfism (MPD) and a broad spectrum of additional abnormalities. Hence, this gene can be promoted to green rating in the next update.

Created: 15 Apr 2026, 10:47 a.m. | Last Modified: 15 Apr 2026, 10:47 a.m.

Panel Version: 7.49

PMID:41962535 (2026) reported the identification of biallelic hypomorphic variants in WDHD1 gene in 17 patients from 14 families with microcephalic primordial dwarfism (MPD) and a broad spectrum of additional abnormalities. All patients had severe IUGR and microcephaly.

The phenotypes in ten patients homozygous for the c.1769−1G>C variant was broad, ranging from foetal lethality to MPD with mild to moderate developmental delay and additional clinical features including severe malformations of multiple organs likely contributing to intrauterine death. The five patients that survived to birth but died as neonates had severe hepatic abnormalities, with acute liver failure (ALF) as the cause of death in four.

Among the seven living subjects, two were homozygous for the c.1769−1G>C variant, while the remaining subjects were compound heterozygous, with combinations of a loss-of-function allele and an intronic or missense variant or two non-coding variants. The most common clinical features among them were postnatal growth retardation, feeding difficulties, developmental delay, a small face with a bulbous nose and retrognathia, a high-pitched voice, and hip dislocation.

There is also functional evidence available from patient-derived fibroblasts which supports the disease association.

This gene has not yet been associated with relevant phenotypes either in OMIM or in Gene2Phenotype (records last accessed 14 April 2026).
Sources: Literature

Created: 15 Apr 2026, 10:45 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
microcephalic osteodysplastic primordial dwarfism, MONDO:0000060

Publications

• 41962535