Neuromuscular Disorders NGS Panel

Turnaround Time

8 weeks

CPT Code(s)

81443

Cost

$3,500

Genes

• Nemaline myopathy
• Arthrogryposis
• Bethlem myopathy
• Centronuclear Myopathy
• Charcot-Marie-Tooth disease
• Congenital Myasthenic syndrome
• Congenital Disorder of Glycosylation
• Dystonia
• Fetal akinesia deformation sequence
• Mitochondrial DNA Depletion Syndrome
• Multiple pterygium syndrome
• Myotonia congenita
• Myotubular myopathy
• Periodic paralysis
• Spastic Paraplegia
• Emery-Dreifuss muscular dystrophy
• Congenital fiber-type disproportion myopathy
• Myoadenylate deaminase deficiency
• Miyoshi muscular dystrophy
• Limb-girdle muscular dystrophy
• Brody myopathy
• Menkes
• Muscular dystrophy-dystroglycanopathy
• Myofibrillar myopathy
• Progressive Encephalopathy
• Distal hereditary motor neuronopathy
• Silver spastic paraplegia syndrome
• Tateyama type of distal myopathy
• Rippling Muscle Disease
• Escobar syndrome
• Myotonia levior
• Compton-North congenital myopathy
• Ullrich congenital muscular dystrophy
• Congenital myosclerosis
• Perry syndrome
• Scapuloperoneal myopathy
• Becker/Duchenne muscular dystrophy
• Lethal congenital contracture syndrome
• Autosomal dominant cerebellar ataxia, deafness, and narcolepsy
• Reducing body myopathy
• Yunis-Varon syndrome
• Giant axonal neuropathy
• Congenital arthrogryposis with anterior horn cell disease
• Nonaka myopathy
• Neuromyotonia and axonal neuropathy
• Danon Disease
• Wilson-Turner syndrome
• Proximal myopathy and ophthalmoplegia
• Laing distal myopathy
• Myosin storage myopathy
• Spheroid body myopathy
• Oculopharyngeal muscular dystrophy
• Muscle glycogenosis
• Neutral lipid storage disease with myopathy
• Congenital generalized lipodystrophy
• McArdle Disease
• Central core disease
• King-Denborough syndrome
• Minicore myopathy with external ophthalmoplegia
• Hyperkalemic periodic paralysis
• Paramyotonia congenita
• Rigid spine muscular dystrophy
• Myoclonic dystonia
• Marinesco-Sjogren syndrome
• Facioscapulohumeral muscular dystrophy
• Welander distal myopathy
• CAP myopathy
• Metatropic dysplasia
• Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia
• Pontocerebellar hypoplasia
• Progressive External Ophthalmoplegia
• Sengers syndrome
• Mitochondrial recessive ataxia syndrome

This panel consists of 144 genes that have been associated with inherited neuromuscular diseases. This panel includes nuclear-encoded mitochondrial genes and select storage-disorder genes. Hereditary neuropathies, including Charcot-Marie-Tooth disease, affect the peripheral nervous system and include symptoms of muscle weakness, decreased reflexes, foot deformities, and loss of sensation. Myopathies are associated with weakness and dysfunction of predominantly proximal skeletal muscles, and wasting may occur in later stages of disease. Congenital myasthenic syndromes are caused by disruptions in the transmission of nerve signals to the muscles, and symptoms may involve weakness of muscles involved in swallowing, speech, and breathing or fatigability upon exertion. The muscular dystrophies tend to display progressive muscle weakness and atrophy due to abnormalities in the cellular maintenance of muscle membranes. These conditions can be inherited in autosomal dominant, autosomal recessive, and X-linked patterns, and each group of disorders exhibits variable clinical presentation, age of onset, degree of severity, and disease progression. In addition to clinical evaluation and genetic testing, diagnosis for these conditions may require electromyogram and nerve conduction studies, muscle biopsy, and CPK and other biochemical testing.

For patients with a specific suspected disorder, individual gene sequencing should be considered first. Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Next Generation Sequencing

The current design of this panel covers all genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts. We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

The preferred sample type is 3-5 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Saliva samples must be submitted in an approved saliva kit. Contact the lab to receive a saliva kit or to have one sent to your patient.

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.