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)
  • 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
  • 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
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
  • 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


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

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