X-linked Myotubular Myopathy: MTM1 Gene Deletion/Duplication

Condition Description

As of March 1, 2021, NTD Genetics will no longer accept samples for this test. For questions, please call: 470-378-2200.

X-linkedmyotubular myopathy (XLMTM) is a non-progressive muscle disease associated withhypotonia, respiratory distress, and delayed motor milestones. Four forms ofthe disease have been described.

  • Severe (classic) XLMTM presents prenatally with polyhydramnios and decreased fetal movement and in newborns with hypotonia and respiratory distress. Affected males have chronic ventilator dependence and grossly delayed motor milestones; they often fail to walk. Infants with severe XLMTM often have typical myopathic facies with dolicocephaly, high forehead, long face with midface hypoplasia, and narrow high-arched palate with subsequent severe malocclusion. Additional features can include length greater than the 90th centile with a proportionately lower weight, long fingers and/toes, cryptorchidism, contractures including clubfeet, areflexia, ptosis, severe myopia, dental malocclusion, and scoliosis. In the absence of significant hypoxic episodes, cognitive development is normal in the majority of individuals. Death in infancy is common.
  • Males with moderate XLMTM achieve motor milestones more quickly than males with the severe form; about 40% require no ventilator support or intermittent support. Males with moderate or even mild disease are at increased risk for respiratory decompensation with intercurrent illness and may require transient or increased ventilatory support. They are also at risk for some of the same medical complications as those with severe XLMTM.
  • Males with mild XLMTM may require ventilatory support only in the newborn period; they have minimally delayed motor milestones, are able to walk, and lack myopathic facies.
  • Adult-onset XLMTM is very rare; affected males do not have clinical manifestations in infancy but develop slowly progressive myopathy in adulthood. They may require respiratory support at night.

Themuscle disease of XLMTM is not progressive; muscle strength improves slowlyover time. Phenotype can vary within a family. Female carriers of XLMTM aregenerally asymptomatic, although rare manifesting heterozygotes have beendescribed, usually due to skewed X-inactivation.

Thediagnosis of XLMTM has traditionally relied upon identification ofcharacteristic histopathologic changes in muscle samples from males withneonatal hypotonia and a family history consistent with X-linked inheritance.These histopathologic changes, however, are not found in all affectedindividuals, and are not specific to XLMTM. An abnormal muscle biopsy is foundin only 50%-70% of obligate carrier females; thus, muscle biopsy studies arenot sensitive enough for carrier testing.

MTM1 (Xq28) is the only gene associatedwith XLMTM; its protein product, myotubularin, is required for muscle celldifferentiation. Molecular genetic testing of MTM1 detects mutations in60%-98% of affected individuals; in individuals with mild XLMTM, fewer than 20%of mutations are identified. Approximately 7% of mutations are large deletionsof one or more exons of MTM1. In simplex cases (i.e., a singleoccurrence in a family), there is a probability of 80%-90% that a woman is acarrier if her son has a confirmed MTM1 mutation. Thus, about 10%-20% ofmales who represent simplex cases have a de novo disease-causingmutation in MTM1 and a mother who is not a carrier. Germline mosaicismhas been reported.

Click here for the GeneTests summary on this condition.

Genes (1)


This test is indicated for:

  • Confirmation of a clinical/biochemical diagnosis of XLMTM in individuals who have tested negative for sequence analysis
  • Carrier testing in adult females with a family history of XLMTM who have tested negative for sequence analysis


DNA isolated from peripheral blood is hybridized to a CGH array to detect deletions and duplications. The targeted CGH array has overlapping probes which cover the entire genomic region.


Detection is limited to duplications and deletions. The CGH array will not detect point or intronic mutations. Results of molecular analysis must be interpreted in the context of the patient's clinical and/or biochemical phenotype.

Specimen Requirements

Listed below are EGL's preferred sample criteria. For any questions, please call 470.378.2200 and ask to speak with a laboratory genetic counselor (eglgc@egl-eurofins.com).
Submit only 1 of the following specimen types
Whole Blood (EDTA)

EDTA (Purple Top)
Infants and Young Children (<2 years of age): 2-3 ml
Children > 2 years of age to 10 years old: 3-5 ml
Older Children & Adults: 5-10 ml
Autopsy: 2-3 ml unclotted cord or cardiac blood
Collection and Shipping
Ship sample at room temperature for receipt at EGL within 72 hours of collection. Do not freeze.
DNA, Isolated

Isolation using the Perkin Elmer™Chemagen™ Chemagen™ Automated Extraction method or Qiagen™ Puregene kit for DNA extraction is recommended.
Collection and Shipping
Refrigerate until time of shipment in 100 ng/µL in TE buffer. Ship sample at room temperature with overnight delivery.

Special Instructions

Submit copies of diagnostic biochemical test results with the sample, if appropriate. Contact the laboratory if further information is needed.

Sequence analysis is required before deletion/duplication analysis by targeted CGH array. If sequencing is performed outside of EGL Genetics, please submit a copy of the sequencing report with the test requisition.

  • Sequencing analysis of the MTM1 gene is available (YZ) and is required before deletion/duplication analysis.
  • ACGH array-based test for deletion/duplication analysis of 64 differentX-linked intellectual disability genes is available (OL).
  • Prenataltesting is available to adult females who are confirmed carriers ofmutations. Please contact the laboratory genetic counselor to discussappropriate testing prior to collecting a prenatal specimen.

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