Invitae Congenital Fiber-Type Disproportion Panel


Test description

The Invitae Congenital Fiber-Type Disproportion Panel analyzes seven genes associated with congenital fiber-type disproportion (CFTD), a form of congenital myopathy. These genes were curated based on the available evidence to date to provide a comprehensive test for this condition.

Individuals with clinical signs and symptoms of CFTD may benefit from diagnostic genetic testing to confirm the diagnosis, provide anticipatory guidance, and inform recurrence risk.

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Primary panel (7 genes)


RYR1: Deletion/duplication analysis is not offered for exons 48 or 49.
SEPN1: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.

Alternative tests to consider

For a broader analysis of genes associated with myopathies, clinicians may consider the Invitae Congenital Myopathy Panel, or the Invitae Comprehensive Myopathy Panel. These broader panels can be ordered at no additional charge.

Congenital fiber-type disproportion (CFTD) is a form of congenital myopathy that typically presents at birth or in the first year of life with hypotonia and mild-to-severe proximal or generalized muscle weakness. Most affected individuals have static, generalized muscle weakness that may improve over time; however, some affected individuals may have slowly progressive muscle weakness. Delayed motor development is common, but the majority of affected individuals are able to achieve independent ambulation. Other findings that may be observed in individuals with CFTD include respiratory issues, feeding difficulties, ophthalmoplegia, contractures, and spinal deformities. Cognitive impairment, cardiac issues, and cryptorchidism are rare features of CFTD. Initially, the core histologic finding associated with CFTD was defined as hypotrophic type 1 muscle fibers that are at least 12% smaller than type 2A or 2B muscle fiber diameters; more recent studies have suggested that the degree of disproportion between type 1 and type 2 fiber size is typically at least 40% in individuals with true CFTD.

In addition to CFTD, these seven genes have been associated with a diverse range of other neuromuscular disorders, with variable clinical and histopathologic findings.

Gene Proportion of CFTD cases Inheritance Other associated neuromuscular conditions
Autosomal dominant Autosomal recessive
ACTA1 <6% Nemaline myopathy 3
LMNA Rare Dilated cardiomyopathy, Emery-Dreifuss muscular dystrophy type 2, limb girdle muscular dystrophy type 1B
MYH7 Unknown Congenital muscular dystrophy, dilated cardiomyopathy, hypertrophic cardiomyopathy, Laing distal myopathy, left ventricular noncompaction, myosin storage myopathy
RYR1 10%–20% Central core disease, multiminicore disease, centronuclear myopathy
SEPN1 Rare Multiminicore disease
TPM2 Rare Nemaline myopathy 4
TPM3 20%–40% Nemaline myopathy 1

The TPM3 and RYR1 genes are the most common known causes of CFTD; together, they account for up to 60% of affected individuals. ACTA1 accounts for less than 6% of affected individuals. The LMNA, MYH7, SEPN1, and TPM3 genes have only been associated with CFTD in a small number of families, and the percentage of affected individuals with CFTD who have variants in these genes is currently unknown.

CFTD is inherited in either an autosomal dominant or an autosomal recessive pattern. CFTD associated with the ACTA1, LMNA, MYH7 and TPM2 genes is inherited in an autosomal dominant pattern. CFTD associated with RYR1 and SEPN1 is inherited in an autosomal recessive pattern. TPM3-associated CFTD can be inherited in either an autosomal dominant or an autosomal recessive pattern. ACTA1- and TPM3-associated CFTD is commonly associated with de novo variants.

Incomplete penetrance has been observed in some of the autosomal dominant forms of CFTD.

CFTD is a rare condition whose prevalence is unknown.

Fiber-type disproportion is not pathognomonic for CFTD and can be observed in other neuromuscular disorders. Genetic testing may be useful in confirming a suspected diagnosis of CFTD or ruling out other disorders with similar findings. A genetic diagnosis may also help predict disease progression and inform recurrence risk.

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
ACTA1 NM_001100.3
LMNA NM_170707.3
MYH7 NM_000257.3
RYR1* NM_000540.2
SEPN1* NM_020451.2
TPM2 NM_003289.3
TPM3 NM_152263.3

RYR1: Deletion/duplication analysis is not offered for exons 48 or 49.
SEPN1: Analysis includes the NM_20451.2:c.*1107T>C variant in the 3' UTR.