Table 2.

Disorders to Consider in the Differential Diagnosis of X-Linked Myotubular Myopathy

DiffDx DisorderGene(s)MOIClinical Features of DiffDx Disorder
Overlapping w/X-MTMDistinguishing from X-MTM
Congenital myotonic dystrophy type 1 DMPK AD
  • Polyhydramnios
  • ↓ fetal movements
  • Hypotonia
  • Myopathic facies
  • Respiratory distress
  • ID
  • Muscle biopsy possibly indistinguishable
  • Absence of ophthalmoparesis
  • AD family history
DNM2-related CNM (OMIM 160150) DNM2 AD
  • Hypotonia
  • Diffuse muscle weakness
  • Ptosis
  • Ophthalmoparesis
  • Myopathic facies
  • Muscle biopsy w/central nuclei
  • Clinical features possibly less severe
  • Normal/reduced growth parameters
  • "Spoke on wheel" changes w/oxidative stains on muscle biopsy
RYR1-related CNM 1 RYR1 AR
  • Neonatal hypotonia
  • Weakness
  • Ophthalmoparesis
  • Ptosis
  • Myopathic facies
  • Severe respiratory compromise
  • Muscle biopsy w/central nuclei
  • Clinical features possibly less severe
  • Normal/reduced growth parameters
  • May have other non-MTM features on biopsy (cores, dystrophic changes)
BIN1-related CNM (OMIM 255200) BIN1 AR
  • Onset in infancy possible
  • Muscle biopsy w/central nuclei
  • Clinical features less severe
  • Normal growth parameters
SPEG-related CNM
(OMIM 615959)		 SPEG1 AR
  • Onset in infancy
  • Diffuse weakness
  • Respiratory failure
  • Ophthalmoparesis
  • Muscle biopsy w/central nuclei
  • Can have prominent cardiac involvement
  • Biopsies may lack central nuclei.
Nemaline myopathy
(OMIM PS161800)		>10 genesAD
AR
  • Can present w/diffuse weakness starting in infancy, often w/prominent facial weakness
  • Biopsies can feature myofiber hypotrophy & type I fiber predominance.
  • Ophthalmoparesis is rare (except in LMOD3-related nemaline myopathy).
  • Muscle biopsy showing nemaline rod aggregates (essentially never seen in X-MTM)
  • Central nuclei usually not ↑
Multiminicore disease (OMIM 606210, 180901) SEPN1
RYR1 		AR 2
  • May present w/diffuse weakness starting from birth
  • Ophthalmoparesis in a subset of persons
  • Weakness usually less than in X-MTM
  • Muscle biopsy showing characteristic disruptions of mitochondrial & sarcotubular organization on oxidative stains (i.e., cores)
  • Central nuclei usually not ↑
Congenital myasthenic syndromes >25 genesAD
AR
  • Can present w/similar symptoms in early childhood, w/facial & extremity weakness & involvement of extraocular muscles
  • Both conditions may respond to mestinon.
  • Electrodiagnostic features of CMS (abnormal repetitive stimulation & jitter on single-fiber EMG) may be seen in X-MTM.
  • Fluctuating weakness variably present in CMS (not typical of X-MTM)
  • Biopsies are either normal or show nonspecific changes; features of X-MTM are not seen on biopsy in CMS.

AD = autosomal dominant; AR = autosomal recessive; CNM = centronuclear myopathy; DiffDx = differential diagnosis; ID = intellectual disability; MOI = mode of inheritance; MTM = myotubular myopathy

1.
2.

The occurrence of minicore myopathy in two generations in a few families – suggestive of autosomal dominant inheritance – has been reported.

From: X-Linked Myotubular Myopathy

Cover of GeneReviews®
GeneReviews® [Internet].
Adam MP, Feldman J, Mirzaa GM, et al., editors.
Seattle (WA): University of Washington, Seattle; 1993-2024.
Copyright © 1993-2024, University of Washington, Seattle. GeneReviews is a registered trademark of the University of Washington, Seattle. All rights reserved.

GeneReviews® chapters are owned by the University of Washington. Permission is hereby granted to reproduce, distribute, and translate copies of content materials for noncommercial research purposes only, provided that (i) credit for source (http://www.genereviews.org/) and copyright (© 1993-2024 University of Washington) are included with each copy; (ii) a link to the original material is provided whenever the material is published elsewhere on the Web; and (iii) reproducers, distributors, and/or translators comply with the GeneReviews® Copyright Notice and Usage Disclaimer. No further modifications are allowed. For clarity, excerpts of GeneReviews chapters for use in lab reports and clinic notes are a permitted use.

For more information, see the GeneReviews® Copyright Notice and Usage Disclaimer.

For questions regarding permissions or whether a specified use is allowed, contact: ude.wu@tssamda.

NCBI Bookshelf. A service of the National Library of Medicine, National Institutes of Health.