Hydrocephalus

Gene: KIF26A

Green List (high evidence)

Comment on list classification: At least 13 patients from 10 families have been described in literature with biallelic variants in KIF26A and KIF26A‐related disorder (PMIDs: 36228617; 36564622; 39305096). 12/12 cases with brain MRI available showed congenital brain malformations - in particular ventriculomegaly/hydrocephalus in 12/12 patients and corpus callosum agenesis / hypoplasia in 7/12 cases.
KIF26A is associated with AR 'Cortical dysplasia, complex, with other brain malformations 11, 620156' in OMIM (accessed 31st Oct 2025). The association of KIF26A and 'complex cortical dysplasia with other brain malformations' is classified as Strong in ClinGen (March 2024). Based on the available evidence, this gene should be promoted to Green on the Hydrocephalus panel.

Created: 3 Nov 2025, 5:30 p.m. | Last Modified: 3 Nov 2025, 5:30 p.m.

Panel Version: 5.3

At least 13 patients from 10 families have been described in literature with biallelic variants in KIF26A and KIF26A‐related disorder (PMIDs: 36228617; 36564622; 39305096).

The heterogenous syndromic presentation may include developmental delay / intellectual disability (6/8, mild to moderate), cardiac defects (6/7), neurological features e.g. hypotonia (2), spasticity (2), paediatric intestinal pseudo‐obstruction (PIPO) (3/13). While only 3/13 patients were diagnosed with PIPO, 8/13 patients had gastrointestinal issues, including megacolon, ischemic small bowels, severe ascites, abdominal distension, vomiting, and intestinal obstruction. Note: several individuals died before certain clinical features could be assessed.

Brain MRI showed Ventriculomegaly/Hydrocephalus in 12/12 patients and corpus callosum agenesis / hypoplasia in 7/12 cases; unavailable in 1 case. Other malformations noted on MRI: Hypogenesis of septum pellucidum, Brainstem patterning disorder, Long midbrain, Small pons, Brain atrophy, Reduced white matter, Bilateral schizencephaly, Absent hippocampal commissure.

PMID: 39305096 Nosrati et al., 2025
Seq method: Trio exome.
Case #1 - 8yo Italian male; at birth: axial hypotonia, poor suction, failed to pass meconium, leading to surgery for Hirschsprung's disease. Compound het c.4378C > T, p.(Arg1460Trp); c.5238C > G, p.(Phe1746Leu).
Case #2 - 6mo Syrian female; presented with abdominal distension and intestinal obstruction symptoms; imaging revealed dilated bowels without mechanical obstruction; biopsies of small and large intestine showed hypoganglionosis. Homozygous for c.4085dup, p.(Ala1363Glyfs*47).
Case #3 - female born to consanguineous parents (Palestinian / Jordanian) - very different presentation: severe spastic quadriplegic cerebral palsy (CP) with epilepsy, hearing problems and cognitive impairments. Homozygous for c.3996C > A, p.(Cys1332*).

PMID: 36564622 Almannai et al., 2023
Seq method: clinical WES.
Report of 2 families with KIF26A‐related disorder.
Family 1: 4 affected individuals, homozygous for c.792dupC, p.(Val265Argfs*5), all presented with persistent abdominal distension and vomiting after birth. 3 individuals died between 2-11 months, 1 patient alive at 3.5 years.
Family 2: proband presented at 3 months with symptoms indicating intestinal obstruction and marked abdominal distension. Symptoms persist at 7yo. Homozygous for c.3330delC, p.(Ser1111Alafs*137).

36228617 Qian et al., 2022
Seq method: WES.
5 unrelated subjects with congenital brain malformations who had inherited biallelic mutations in KIF26A
A01 - consanguineous Turkish family, microcephaly (−3.45SD) and an MRI suggesting a component of cerebral atrophy, as well as dysmorphic features and ileus with megacolon. Homozygous for c.3440dupC, p.Ala1148Cysfs*20.
B01 - diagnosed prenatally with bilateral schizencephaly at 21 weeks; pregnancy terminated; compound heterozygous c.2161C>T, p.Arg721Cys, and c.4676C>T, p.Ala1559Val
C01 - male, non-consanguineous parents, presented with mild developmental delay and learning disability. Brain MRI at 18 years demonstrated agenesis of the corpus callosum; compound het KIF26A: c.4676C>T, p.Arg1624Cys, and c.4870C>T, p.Ala1559Val
D01 - was diagnosed with polymicrogyria and hydrocephalus, with inherited compound heterozygous variants in KIF26A: c.2845C>T, p.Pro949Ser, and c.4676C>T, p.Ala1559Val
E01 - male born to consanguineous parents with growth retardation and developmental delay. Brain MRI performed at 18 months revealed a thin CC, ventriculomegaly and polymicrogyria; homozygous for c.4804C>T; p.Arg1602Trp.

KIF26A is associated with Cortical dysplasia, complex, with other brain malformations 11, 620156 in OMIM (accessed 31st Oct 2025).
The association of KIF26A and 'complex cortical dysplasia with other brain malformations' is classified as Strong in ClinGen (March 2024).

Created: 3 Nov 2025, 5:29 p.m. | Last Modified: 3 Nov 2025, 5:34 p.m.

Panel Version: 5.3

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156; cortical dysplasia, complex, with other brain malformations 11 MONDO:0859332

Publications

• 36228617
• 36564622
• 39305096