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Hydrocephalus v5.11 FAAP100 Ida Ertmanska gene: FAAP100 was added
gene: FAAP100 was added to Hydrocephalus. Sources: Literature
Q1_26_promote_green tags were added to gene: FAAP100.
Mode of inheritance for gene: FAAP100 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: FAAP100 were set to 40232843; 40244696
Phenotypes for gene: FAAP100 were set to Fanconi anemia, complementation group X, OMIM:621258
Review for gene: FAAP100 was set to GREEN
Added comment: PMID: 40232843 Kuehl et al., 2025
Report of a consanguineous family including a fetus homozygous for FAAP100 c.1642A>C p.(T542P). Proband phenotype: growth retardation, radial ray defects, duodenal atresia, ventricular septal defect, and hydrocephalus; cellular hypersensitivity to ICL induction by mitomycin C - consistent with FA spectrum.
Functional studies: Faap100-/- mice exhibited embryonic lethality, microsomia, malformations, and gonadal atrophy resembling mice with established Fanconi anemia subtypes. Also, faap100–/– zebrafish show a complete female-to-male sex reversal, consistent with 17 other zebrafish fanc gene–KO models.

PMID: 40244696 Harrison et al., 2025
Family 1: consanguineous, presented with a history of 8 pregnancies, 6 of which resulted in spontaneous abortion and 2 that resulted in death of the infant soon after birth; liveborn children presented with severe developmental and hematologic abnormalities: prenatal ventriculomegaly, absent right kidney, IUGR, multiple limb abnormalities, and cardiac defects in 1st pregnancy; and severe IUGR, hydrocephalus, multicystic dysplastic kidneys, a contracted and hypoplastic urinary bladder, and an imperforate anus in 2nd pregnancy.
Chromosome breakage studies showed 2.94 breaks/chromosome in individual A (control = 0.06) - result consistent with Fanconi anemia.
Both sibs were homozygous for FAAP100 variant c.1151_1161del; p.E384Gfs*28; parents confirmed het.

Family 2: nonconsanguineous parents with history of 2 spontaneous abortions and a female child (individual C) that died at 14 months due to respiratory failure. Individual C presented with presented with congenital anomalies including bilateral microtia, reduced radius size in both forearms, absence of both thumbs, and a right radial club hand. Severe anomalies detected in individual D on a prenatal scan: bilateral cerebral lateral ventriculomegaly, a dysplastic pancreatic tail, bilateral ectopic kidneys, and incomplete lung lobation - pregnancy was terminated. Individual D was found to be homozygous for c.2590C>T (p.Gln864Ter). Variant is in the stretch of homozygosity, suggesting a founder effect; parents confirmed het.

FAAP100 is linked to Fanconi anemia, complementation group X, MIM:621258 (OMIM accessed 23rd Feb 2026).
Sources: Literature
Hydrocephalus v5.3 KIF26A Ida Ertmanska changed review comment from: 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).
Sources: Other; to: 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).
Hydrocephalus v5.2 KIF26A Ida Ertmanska gene: KIF26A was added
gene: KIF26A was added to Hydrocephalus. Sources: Other
Q4_25_promote_green tags were added to gene: KIF26A.
Mode of inheritance for gene: KIF26A was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIF26A were set to 36228617; 36564622; 39305096
Phenotypes for gene: KIF26A were set to Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156; cortical dysplasia, complex, with other brain malformations 11 MONDO:0859332
Review for gene: KIF26A was set to GREEN
Added comment: 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).
Sources: Other
Hydrocephalus v4.6 ERF Arina Puzriakova Tag to_be_confirmed_NHSE was removed from gene: ERF.
Hydrocephalus v4.6 ERF Arina Puzriakova reviewed gene: ERF: Rating: RED; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v4.5 ERF Arina Puzriakova Source Expert Review Red was added to ERF.
Rating Changed from Green List (high evidence) to Red List (low evidence)
Hydrocephalus v4.3 ERF Achchuthan Shanmugasundram Tag Q2_21_rating was removed from gene: ERF.
Tag Q2_21_expert_review was removed from gene: ERF.
Hydrocephalus v2.132 ERF Eleanor Williams commented on gene: ERF
Hydrocephalus v2.132 ERF Eleanor Williams Tag Q2_21_rating tag was added to gene: ERF.
Hydrocephalus v2.127 ERF Sarah Leigh reviewed gene: ERF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: ; Mode of inheritance: None
Hydrocephalus v2.127 ERF Sarah Leigh Tag to_be_confirmed_NHSE tag was added to gene: ERF.
Hydrocephalus v2.114 ERF Ivone Leong Tag Q2_21_expert_review tag was added to gene: ERF.
Hydrocephalus v2.31 ERF Ivone Leong Phenotypes for gene: ERF were changed from Craniosynostosis 4 600775 to Craniosynostosis 4, OMIM:600775
Hydrocephalus v2.8 KIDINS220 Eleanor Williams gene: KIDINS220 was added
gene: KIDINS220 was added to Hydrocephalus. Sources: Literature
Mode of inheritance for gene: KIDINS220 was set to BIALLELIC, autosomal or pseudoautosomal
Publications for gene: KIDINS220 were set to 32909676; 33205811; 28934391; 22048169
Phenotypes for gene: KIDINS220 were set to brain ventriculomegaly and limb contractures
Review for gene: KIDINS220 was set to GREEN
Added comment: Associated with Spastic paraplegia, intellectual disability, nystagmus, and obesity #617296 in OMIM for monoallelic cases.

3 biallelic cases associated with cerebral ventriculomegaly and limb contractures, plus a mouse model that shows some phenotypic overlap:

PMID: 32909676 - El-Dessouky et al 2020 - report a consanguineous family of Egyptian origin with several miscarriages. Prenatal ultrasonography revealed limb contractions and ventriculomegaly aswell as cerebellar anomalies, cardiac anomalies and hydrops fetalis. Using WES a homozygous deleterious frameshift variant (c.208del; p.Asp70Ilefs*18) in KIDINS220 gene was identified. Both parents were heterozygous for this variant.

PMID: 33205811 - Jacquemin et al 2021 - report a consanguineous family of Pakistani origin in which 3 fetuses presented with brain ventriculomegaly and limb contractures. Autopsy of one fetus identifed bilateral club feet and club hands. They were found by WES to share a very rare homozygous variant of KIDINS220 (c.2327_2336del, Gln713_Leu715del). Parents and healthy siblings were heterozygous for this variant. Severe ventriculomegaly was diagnosed as early as 14 weeks. Binding of KIDINS220 to TrkA is decreased by the deletion mutation.

PMID: 28934391 - Mero et al 2017 - report a consanguineous couple in which 4 fetuses presented with enlarged cerebral ventricles and limb contractures. Exome sequencing in two of the fetuses found a shared homozygous frameshift variant in exon 24 in KIDINS220 ((NM_020738:c.3394_3403del; p.Gln1132Serfs*30). Healthy family members were either carriers or homozygous for the wild-type allele. It is thought that the variant leads to NMD and complete loss of KIDINS220 protein.

PMID: 22048169 - Cesca et al 2011 - report a Kidins220 mutant mouse. Kidins220 -/- mice die at late stages of gestation and show extensive neuronal cell death in the central and peripheral nervous systems, as well as heart malformations.
Sources: Literature
Hydrocephalus v2.5 ERF Zornitza Stark reviewed gene: ERF: Rating: RED; Mode of pathogenicity: None; Publications: ; Phenotypes: Craniosynostosis 4, MIM# 600775; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Hydrocephalus v1.34 ERF Louise Daugherty reviewed gene: ERF: Rating: AMBER; Mode of pathogenicity: ; Publications: ; Phenotypes: ; Mode of inheritance:
Hydrocephalus v1.33 ERF Louise Daugherty Source NHS GMS was added to ERF.
Hydrocephalus ERF Helen Brittain marked ERF as ready
Hydrocephalus ERF Helen Brittain classified ERF as green
Hydrocephalus ERF Helen Brittain added ERF to panel
Hydrocephalus ERF Helen Brittain reviewed ERF