Congenital muscular dystrophy
Gene: FHL1
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 dystrophyCreated: 19 Mar 2024, 3:29 p.m. | Last Modified: 11 Apr 2024, 4:10 p.m.
Panel Version: 4.23
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 myopathyCreated: 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
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 ReviewCreated: 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
Phenotypes for gene: FHL1 were changed from 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 to Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, OMIM:300717
Publications for gene: FHL1 were set to
Source NHS GMS was added to FHL1.
Gene: fhl1 has been classified as Green List (High Evidence).
gene: FHL1 was added gene: FHL1 was added to Congenital muscular dystrophy. Sources: Expert Review Mode of inheritance for gene: FHL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Phenotypes for gene: FHL1 were set to 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 Review for gene: FHL1 was set to AMBER