Paediatric pseudo-obstruction syndrome

Gene: MYH11

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BOTH monoallelic and biallelic, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 7:44 a.m. | Last Modified: 1 Feb 2023, 7:44 a.m.

Panel Version: 0.216

Comment on rating: The rating should be GREEN as this gene has been implicated in both Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 (MIM #619351) and Visceral myopathy 2 (MIM #619350) from at least three unrelated cases, and supported by functional studies from animal models.

Autosomal dominant variants in MYH11 was identified from a family of 13 member over three generations and reported with chronic intestinal pseudoobstruction (CIPO) (PMID:31389005). Similarly, two other families were reported with autosomal dominant variants resulting in smooth muscle dysmotility syndrome with severe esophageal, gastric, and intestinal disease (PMID:31944481).

At least three unrelated cases were also reported with autosomal recessive variants in MYH11 gene. An Algerian infant died with MMIHS was identified with a homozygous nonsense variant K1200X (PMID:25407000), while another infant died at 18 months with MMIHS was identified with compound heterozygous frameshift variants (PMID:29575632). In addition, compound heterozygous missense variants were identified in three male foetuses that were reported with progressive megacystis and oligohydramnios from prenatal ultrasound (PMID:31427716).

Complete Myh11 knockout in mouse models caused death within three days of birth and mouse phenotypes are consistent with multisystem smooth muscle dysfunction.

This gene has been associated with both conditions in OMIM and with Megacystis-microcolon-intestinal hypoperistalsis syndrome in G2P.

Created: 29 Dec 2022, 7:13 p.m. | Last Modified: 29 Dec 2022, 7:13 p.m.

Panel Version: 0.85

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Megacystis-microcolon-intestinal hypoperistalsis syndrome 2, OMIM:619351; Visceral myopathy 2, OMIM:619350

Publications

• 25407000
• 29575632
• 31044419
• 31389005
• 31427716
• 31848803
• 31944481
• 33729000

Review submitted on behalf of Dr. Anna Rybak and Dr. Osvaldo Borreli, Great Ormond Street Hospital for Children NHS Foundation Trust. Gene group: Myopathic PIPO/MMIHS. Protein function: enteric smooth muscle actingamma 2.

Created: 20 Dec 2022, 3:32 p.m. | Last Modified: 20 Dec 2022, 3:32 p.m.

Panel Version: 0.2

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Abnormal MYH11 in smooth muscle myosin leads to impaired contractility

Publications

• 33729000
• 31848803