Activity

Filter

Cancel
Date Panel Item Activity
20 actions
Paediatric pseudo-obstruction syndrome v2.4 KIF26A Ida Ertmanska Phenotypes for gene: KIF26A were changed from GDNF-Ret in ENS development to Cortical dysplasia, complex, with other brain malformations 11, OMIM:620156; cortical dysplasia, complex, with other brain malformations 11 MONDO:0859332
Paediatric pseudo-obstruction syndrome v2.1 KIF26A Ida Ertmanska changed review comment from: 13 patients from have been described in literature with biallelic variants in KIF26A and KIF26A‐related disorder (PMIDs: 39305096

The heterogenous syndromic presentation may include developmental delay / intellectual disability (6/13, mild to moderate), cardiac defects (6/13), neurological features e.g. hypotonia (2), spasticity (2), paediatric intestinal pseudo‐obstruction (PIPO) (3/13). While only 3/13 patients were diagnosed with PIPO, 3 others had other gastrointestinal issues: megacolon, ischemic small bowels, severe ascites, abdominal distension, vomiting, and intestinal obstruction.
Brain MRI showed Ventriculomegaly/Hydrocephalus in 12/13 patients and corpus callosum agenesis / hypoplasia in 7/13 cases.

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. Post‐surgery, he had decreased stool frequency managed with macrogol; histopathological examination revealed features consistent with PIPO diagnosis. 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
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 Q

KIF26A is associated with Cortical dysplasia, complex, with other brain malformations 11, 620156 in OMIM (accessed 31st Oct 2025).; 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).

Note: several individuals died before certain clinical features could be assessed. 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.
Brain MRI showed Ventriculomegaly/Hydrocephalus in 12/13 patients and corpus callosum agenesis / hypoplasia in 7/13 cases.

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. Post‐surgery, he had decreased stool frequency managed with macrogol; histopathological examination revealed features consistent with PIPO diagnosis. 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).
Paediatric pseudo-obstruction syndrome v0.216 RET Achchuthan Shanmugasundram commented on gene: RET: The rating of this gene has been updated to Green and the mode of inheritance set to 'MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown' following NHS Genomic Medicine Service approval.
Paediatric pseudo-obstruction syndrome v0.198 KIF26A Arina Puzriakova Phenotypes for gene: KIF26A were changed from to GDNF-Ret in ENS development
Paediatric pseudo-obstruction syndrome v0.154 SUCLG1 Achchuthan Shanmugasundram edited their review of gene: SUCLG1: Added comment: Comment on list classification: This gene should be rated RED as I do not see any association of this gene with intestinal dysmotility and pseudo-obstruction.

This gene has been associated with mitochondrial DNA depletion syndrome 9 (encephalomyopathic with or without methylmalonic aciduria) (MIM #245400) in OMIM. However, this disorder is characterised by infantile onset of hypotonia, lactic acidosis, severe psychomotor retardation, progressive neurologic deterioration, and excretion of methylmalonic acid. Although other frequent manifestations include feeding difficulty and gastroesophageal reflux, there is no clear indication of any links of this disorder with either pseudo-obstruction or intestinal dysmotility.; Changed rating: RED
Paediatric pseudo-obstruction syndrome v0.125 RET Achchuthan Shanmugasundram Phenotypes for gene: RET were changed from to {Hirschsprung disease, susceptibility to, 1}, 142623; {Hirschsprung disease, protection against}, 142623
Paediatric pseudo-obstruction syndrome v0.124 RET Achchuthan Shanmugasundram Publications for gene: RET were set to
Paediatric pseudo-obstruction syndrome v0.123 RET Achchuthan Shanmugasundram Mode of inheritance for gene: RET was changed from to MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.122 RET Achchuthan Shanmugasundram Classified gene: RET as Green List (high evidence)
Paediatric pseudo-obstruction syndrome v0.122 RET Achchuthan Shanmugasundram Gene: ret has been classified as Green List (High Evidence).
Paediatric pseudo-obstruction syndrome v0.121 RET Achchuthan Shanmugasundram reviewed gene: RET: Rating: GREEN; Mode of pathogenicity: None; Publications: 21960833, 31848803, 34092334, 36521661; Phenotypes: {Hirschsprung disease, susceptibility to, 1}, 142623, {Hirschsprung disease, protection against}, 142623; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.73 LMOD1 Achchuthan Shanmugasundram changed review comment from: Comment on classification of this gene: This gene should be rated GREEN, as this gene has been implicated in megacystis microcolon intestinal hypoperistalsis syndrome in two unrelated patients and is supported by evidence from mouse model.

A dutch female infant identified with homozygous nonsense variant (p.R370X) died at 5 days of life. Both her parents were heterozygous for the same variant. The clinical presentations include distended and lax abdominal wall, with palpable intestines, bladder distention, bilateral distention of the proximal ureters, and hydronephrosis (PMID:28292896).

A male infant with compound heterozygous missense variants (p.T369M; p.R421H) was also presented with typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon (PMID:35170814).

A mouse model with a similar Lmod1 mutation, engineered with CRISPR-Cas9 genome editing, exhibited the same gastrointestinal and urinary bladder phenotypes as seen in the dutch female infant (PMID:28292896).; to: Comment on classification of this gene: This gene should be rated GREEN, as this gene has been implicated in megacystis microcolon intestinal hypoperistalsis syndrome in two unrelated patients and is supported by evidence from mouse model.

A dutch female infant identified with homozygous nonsense variant (p.R370X) died at 5 days of life. Both her parents were heterozygous for the same variant. The clinical presentations include distended and lax abdominal wall, with palpable intestines, bladder distention, bilateral distention of the proximal ureters, and hydronephrosis (PMID:28292896).

A male infant with compound heterozygous missense variants (p.T369M; p.R421H) was also presented with typical symptoms of pediatric intestinal pseudo-obstruction (PIPO) but without megacystis and microcolon (PMID:35170814).

A mouse model with a similar Lmod1 mutation, engineered with CRISPR-Cas9 genome editing, exhibited the same gastrointestinal and urinary bladder phenotypes as seen in the dutch female infant (PMID:28292896).

This gene-disease association has already been reported in OMIM.
Paediatric pseudo-obstruction syndrome v0.58 L1CAM Achchuthan Shanmugasundram commented on gene: L1CAM: Added a 'monogenic-polygenic' tag based on patient in PMID:22344793 who carried both L1CAM and RET variants.
Paediatric pseudo-obstruction syndrome v0.17 BCR Arina Puzriakova Added comment: Comment on list classification: Not associated with any relevant phenotype in OMIM or G2P. Only a single patient has been reported in literature (PMID: 34190380) with paediatric intestinal pseudo-obstruction and a heterozygous de novo variant (c.3072+1G>A). Bcr null mice did display growth retardation and impaired gastrointestinal motility but additional patients required prior to adding as diagnostic-grade.
Paediatric pseudo-obstruction syndrome v0.2 RET Eleanor Williams reviewed gene: RET: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Gain in function mutation associated with intestinal ganglioneuromas leading to increased cell number in the myenteric plexus and dysmotility; Mode of inheritance: MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Paediatric pseudo-obstruction syndrome v0.2 RAD21 Eleanor Williams reviewed gene: RAD21: Rating: ; Mode of pathogenicity: ; Publications: 31848803; Phenotypes: Pseudo-obstruction, megaduodenum, long segment Barretts esophagus and cardiac abnormalities; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal
Paediatric pseudo-obstruction syndrome v0.2 KIF26A Eleanor Williams reviewed gene: KIF26A: Rating: ; Mode of pathogenicity: ; Publications: 30663199; Phenotypes: GDNF-Ret in ENS development; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 DDX3X Eleanor Williams reviewed gene: DDX3X: Rating: ; Mode of pathogenicity: ; Publications: 32896648; Phenotypes: Psychomotor retardation, severe constipation, and a recurrent paralytic ileus.; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.2 BCR Eleanor Williams reviewed gene: BCR: Rating: ; Mode of pathogenicity: ; Publications: 34190380; Phenotypes: Growth retardation and impaired gastrointestinal motility; Mode of inheritance: Unknown
Paediatric pseudo-obstruction syndrome v0.1 RET Eleanor Williams gene: RET was added
gene: RET was added to Paediatric pseudo-obstruction syndrome. Sources: Expert list
Mode of inheritance for gene: RET was set to