Congenital muscular dystrophy and congenital myopathy

Gene: FHL1

Green List (high evidence)

In response to Zornitza Starks' review, Helen Brittain (Genomics England Clinical Fellow) was asked the following question: are the phenotypes of Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset (OMIM:300717) and/or Reducing body myopathy, X-linked 1b, with late childhood or adult onset (OMIM:300718), which are associated with FHL1 variants, appropriate for this panel - Congenital muscular dystrophy (R79)? Helen Brittain replied that in PMID: 19181672, the patients present with weakness and a raised CK - this would make clinicians think of a muscular dystrophy primarily. Although technically it may be a myopathy, I think it is enough of a mimic to be included on both the dystrophy and myopathy panels. Therefore this gene should remain green on Congenital muscular dystrophy and congenital myopathy (R432) also.

Created: 20 May 2024, 12:22 p.m. | Last Modified: 20 May 2024, 12:24 p.m.

Panel Version: 0.236

I don't know

PMID: 19181672 - 11 patients (9 families) with reducing body myopathy. All patients had progressive muscle weakness with 7/11 having onset <5 years old. Majority had proximal muscle weakness with elevated CK levels. Authors note "we would be hesitant to use the term dystrophic for this myopathy as the mechanisms of cell damage remain to be fully worked out"
p.His123 is a hotspot with recurring de novo missense mutations at this residue.

PMID: 19171836 - 5 patients with reducing body myopathy, 2/5 had fatal infantile forms of disease.

Summary: congenital onset reported, however uncertain if this is as a dystrophy or only myopathy

Created: 24 Jun 2020, 9:08 a.m. | Last Modified: 24 Jun 2020, 9:08 a.m.

Panel Version: 2.4

Mode of inheritance
X-LINKED: hemizygous mutation in males, biallelic mutations in females

Phenotypes
Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717

Publications

• 19181672
• 19171836

I don't know

Comment on list classification: Green gene recommended by Anna Sarkozy as a result of GLH Test Group prior to sign off. Noted causing a very severe early onset condition.

Created: 4 Dec 2019, 12:58 p.m. | Last Modified: 4 Dec 2019, 12:58 p.m.

Panel Version: 1.72

gene recommended to be added to panel by Anna Sarkozy as a result of GLH Test Group prior to sign off
Sources: Expert Review

Created: 4 Dec 2019, 12:58 p.m.

Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)

Phenotypes
Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, 300717; Reducing body myopathy, X-linked 1b, with late childhood or adult onset, 300718