Congenital muscular dystrophy

Gene: TRAPPC2L

I don't know

Comment on list classification: While there are 4 unrelated families reported with biallelic TRAPPC2L variants, the main clinical presentation was global developmental delay. Episodic rhabdomyolysis was noted in 2 patients (homozygous for the same variant), and congenital hypotonia with elevated CK was seen in a third family. However, more evidence is required to confirm that these patients have TRAPPC2L-related muscular dystrophy. Hence, this gene should remain Amber with the current evidence.

Created: 17 Jun 2026, 1:24 p.m. | Last Modified: 17 Jun 2026, 1:26 p.m.

Panel Version: 7.18

PMID: 30120216 Milev et al., 2018
Two unrelated probands with homozygous missense (c.109G>T, p.Asp37Tyr) variant in TRAPPC2L. Both individuals presented neurodevelopmental delay, febrile illness-induced encephalopathy, and episodic rhabdomyolysis, followed by developmental arrest, seizures and tetraplegia. The variant segregated with the phenotype in each family, and haplotype analysis suggested a founder effect.

PMID: 32843486 Al-Deri et al., 2020
Ashkenazi Jewish family with three affected sibs with GDD/ID, WGS revealed a segregating homozygous missense variant (c.5G>C, p.Ala2Gly) in the TRAPPC2L gene. No seizures, brain MRI abnormalities, or illness provoked regression were documented in this family.
The siblings have not had their serum creatine kinase levels measured, and there been no manifestations of a myopathy.

PMID: 36849228 Abaji et al., 2023
2 sibs (boy and girl) with a neurodevelopmental disorder - both had severe developmental delay (absent speech, walking absent in IV-3, sister IV-4 started walking at 7-9 years old), hypotonia, mild dysmorphic features, non-specific MRI changes (e.g., thin corpus callosum, delayed myelination), stereotyped hand movements. No regression of skills was noted. WES revealed a homozygous c.367C>T, p.Gln123Ter variant in TRAPPC2L. Unaffected family members confirmed WT / het. Both patients had elevated CK, but muscle biopsy in patient IV-4 showed normal morphology and no histoenzymatic alterations. Authors argue it may be too early in life to see musculary dystrophy features on biopsy.

TRAPPC2L is associated with AR Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, MIM:618331 (OMIM accessed 17th Jun 2026).

Created: 17 Jun 2026, 1:21 p.m. | Last Modified: 17 Jun 2026, 1:21 p.m.

Panel Version: 7.15

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis, OMIM:618331

Publications

• 30120216
• 32843486
• 36849228

I don't know

Encephalopathy, progressive, early-onset, with episodic rhabdomyolysis.

Created: 27 May 2026, 9:42 a.m. | Last Modified: 27 May 2026, 9:42 a.m.

Panel Version: 7.9

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal