Holoprosencephaly

Gene: CDK20

Red List (low evidence)

PMID:42409022 (2026) reported a cohort of seven individuals from five unrelated families including five deceased foetuses and two living children presenting with a consistent pattern of multisystem anomalies.

Recurrent prenatal findings included severe ventriculomegaly or holoprosencephaly, midline cleft lip and palate, cryptophthalmos and/or anophthalmia, and limb anomalies, resulting in a decision to terminate the pregnancy. Postmortem examinations demonstrated a spectrum of brain malformations, including aqueduct stenosis, agenesis of the olfactory bulb and tract, absent pituitary stalk, corticospinal tract abnormalities, corpus callosum abnormalities, absent septum pellucidum, polydactyly and a sandal toe gap. The two living individuals showed overlapping features, including structural brain anomalies, panhypopituitarism, genital anomalies, and severe global developmental delay. Semilobar holoprosencephaly was identified by ultrasound in one foetus (family III).

These families were identified with either homozygous or compound heterozygous variants in CDK20 gene, with six variants in total.

Immunoblot analysis of fibroblasts derived from two affected fetuses with the homozygous c.687+6T>C variant demonstrated reduced CDK20 levels, and were significantly deficient in cilium formation and function, with abnormal cilium morphology and significantly decreased Hedgehog responsiveness.

This gene has not yet been associated with any relevant phenotypes either in OMIM (last accessed 23 July 2026) or in Gene2Phenotype.
Sources: Literature

Created: 23 Jul 2026, 12:34 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
ciliopathy, MONDO:0005308; Ventriculomegaly, HP:0002119; hydrocephalus, MONDO:0001150; holoprosencephaly, MONDO:0016296

Publications

• 42409022