X-linked myotubular myopathy

X-linked myotubular myopathy
Classification and external resources
OMIM	310400

X-linked myotubular myopathy (MTM) is a form of centronuclear myopathy (CNM) associated with myotubularin 1.

Genetically inherited traits and conditions are often referred to based upon whether they are located on the "sex chromosomes" (the X or Y chromosomes) versus whether they are located on "autosomal" chromosomes (chromosomes other than the X or Y). Thus, genetically inherited conditions are categorized as being sex-linked (e.g., X-linked) or autosomal. Females have two X-chromosomes, while males only have a single X chromosome, and a genetic abnormality located on the X chromosome is much more likely to cause clinical disease in a male (who lacks the possibility of having the normal gene present on any other chromosome) than in a female (who is able to compensate for the one abnormal X chromosome).

The X-linked form of MTM is the most commonly diagnosed type. Almost all cases of X-linked MTM occurs in males. Females can be "carriers" for an X-linked genetic abnormality, but usually they will not be clinically affected themselves. Two exceptions for a female with a X-linked recessive abnormality to have clinical symptoms: one is a manifesting carrier and the other is X-inactivation. A manifesting carrier usually has no noticeable problems at birth; symptoms show up later in life. In X-inactivation, the female (who would otherwise be a carrier, without any symptoms), actually presents with full-blown X-linked MTM. Thus, she congenitally presents (is born with) MTM.^[1] Thus, although MTM1 mutations most commonly cause problems in boys, these mutations can also can clinical myopathy in girls, for the reasons noted above. Girls with myopathy and a muscle biopsy showing a centronuclear pattern should be tested for MTM1 mutations.^[1]

Many clinicians and researchers use the abbreviations XL-MTM, XLMTM or X-MTM to emphasize that the genetic abnormality for myotubular myopathy (MTM) is X-linked (XL), having been identified as occurring on the X chromosome. The specific gene on the X chromosome is referred to as MTM-1. In theory, some cases of CNM may be caused by an abnormality on the X chromosome, but located at a different site from the gene MTM1, but currently MTM1 is the only X-linked genetic mutation site identified for myotubular or centronuclear myopathy. Clinical suspicion for X-linked inheritance would be a disease affecting multiple boys (but no girls) and a pedigree chart showing inheritance only through the maternal (mother’s) side of each generation.

References

1 2 Jungbluth H, Sewry C, Buj-Bello A, Kristiansen M, Ørstavik K, Kelsey A, Manzur A, Mercuri E, Wallgren-Pettersson C, Muntoni F (2003). "Early and severe presentation of X-linked myotubular myopathy in a girl with skewed X-inactivation". Neuromuscul Disord. 13 (1): 55–9. doi:10.1016/S0960-8966(02)00194-3. PMID 12467733.

External links

Diseases of myoneural junction and muscle / neuromuscular disease (G70–G73, 358–359)

Neuromuscular-
junction disease

autoimmune
- Myasthenia gravis
- Lambert–Eaton myasthenic syndrome

Myopathy/
congenital myopathy

Muscular dystrophy
(DAPC)

AD	Limb-girdle muscular dystrophy 1 Oculopharyngeal Facioscapulohumeral Myotonic Distal (most)

AR	Limb-girdle muscular dystrophy 2 Congenital Fukuyama Ullrich Walker–Warburg

XR	dystrophin Becker's Duchenne Emery–Dreifuss

Other structural

Channelopathy

Myotonia	Myotonia congenita Thomsen disease Neuromyotonia/Isaacs syndrome Paramyotonia congenita

Periodic paralysis	Hypokalemic Thyrotoxic Hyperkalemic

Other	Central core disease

Mitochondrial myopathy

Other

Inflammatory myopathy

Sex linkage: X-linked disorders

X-linked recessive

Immune	Chronic granulomatous disease (CYBB) Wiskott–Aldrich syndrome X-linked severe combined immunodeficiency X-linked agammaglobulinemia Hyper-IgM syndrome type 1 IPEX X-linked lymphoproliferative disease Properdin deficiency

Hematologic	Haemophilia A Haemophilia B X-linked sideroblastic anemia

Endocrine	Androgen insensitivity syndrome/Spinal and bulbar muscular atrophy KAL1 Kallmann syndrome X-linked adrenal hypoplasia congenita

Metabolic	Amino acid: Ornithine transcarbamylase deficiency Oculocerebrorenal syndrome Dyslipidemia: Adrenoleukodystrophy Carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency Pyruvate dehydrogenase deficiency Danon disease/glycogen storage disease Type IIb Lipid storage disorder: Fabry's disease Mucopolysaccharidosis: Hunter syndrome Purine-pyrimidine metabolism: Lesch–Nyhan syndrome Mineral: Menkes disease/Occipital horn syndrome

Nervous system	X-linked mental retardation: Coffin–Lowry syndrome MASA syndrome Alpha-thalassemia mental retardation syndrome Siderius X-linked mental retardation syndrome Eye disorders: Color blindness (red and green, but not blue) Ocular albinism (1) Norrie disease Choroideremia Other: Charcot–Marie–Tooth disease (CMTX2-3) Pelizaeus–Merzbacher disease SMAX2

Skin and related tissue	Dyskeratosis congenita Hypohidrotic ectodermal dysplasia (EDA) X-linked ichthyosis X-linked endothelial corneal dystrophy

Neuromuscular	Becker's muscular dystrophy/Duchenne Centronuclear myopathy (MTM1) Conradi–Hünermann syndrome Emery–Dreifuss muscular dystrophy 1

Urologic	Alport syndrome Dent's disease X-linked nephrogenic diabetes insipidus

Bone/tooth	AMELX Amelogenesis imperfecta

No primary system	Barth syndrome McLeod syndrome Smith–Fineman–Myers syndrome Simpson–Golabi–Behmel syndrome Mohr–Tranebjærg syndrome Nasodigitoacoustic syndrome

X-linked dominant

X-linked hypophosphatemia Focal dermal hypoplasia Fragile X syndrome Aicardi syndrome Incontinentia pigmenti Rett syndrome CHILD syndrome Lujan–Fryns syndrome Orofaciodigital syndrome 1 Craniofrontonasal dysplasia

Deficiencies of intracellular signaling peptides and proteins

GTP-binding protein regulators

GTPase-activating protein	Neurofibromatosis type I Watson syndrome Tuberous sclerosis

Guanine nucleotide exchange factor	Marinesco–Sjögren syndrome Aarskog–Scott syndrome Juvenile primary lateral sclerosis X-Linked mental retardation 1

G protein

Heterotrimeic	cAMP/GNAS1: Pseudopseudohypoparathyroidism Progressive osseous heteroplasia Pseudohypoparathyroidism Albright's hereditary osteodystrophy McCune–Albright syndrome CGL 2

Monomeric	RAS: HRAS Costello syndrome KRAS Noonan syndrome 3 KRAS Cardiofaciocutaneous syndrome RAB: RAB7 Charcot–Marie–Tooth disease RAB23 Carpenter syndrome RAB27 Griscelli syndrome type 2 RHO: RAC2 Neutrophil immunodeficiency syndrome ARF: SAR1B Chylomicron retention disease ARL13B Joubert syndrome 8 ARL6 Bardet–Biedl syndrome 3

MAP kinase

Cardiofaciocutaneous syndrome

Other kinase/phosphatase

Tyrosine kinase	BTK X-linked agammaglobulinemia ZAP70 ZAP70 deficiency

Serine/threonine kinase	RPS6KA3 Coffin-Lowry syndrome CHEK2 Li-Fraumeni syndrome 2 IKBKG Incontinentia pigmenti STK11 Peutz–Jeghers syndrome DMPK Myotonic dystrophy 1 ATR Seckel syndrome 1 GRK1 Oguchi disease 2 WNK4/WNK1 Pseudohypoaldosteronism 2

Tyrosine phosphatase	PTEN Bannayan–Riley–Ruvalcaba syndrome Lhermitte–Duclos disease Cowden syndrome Proteus-like syndrome MTM1 X-linked myotubular myopathy PTPN11 Noonan syndrome 1 LEOPARD syndrome Metachondromatosis

Signal transducing adaptor proteins

Other

NF2
- Neurofibromatosis type II
NOTCH3
- CADASIL
PRKAR1A
- Carney complex
PRKAG2
- Wolff–Parkinson–White syndrome
PRKCSH
- PRKCSH Polycystic liver disease
XIAP
- XIAP2

See also intracellular signaling peptides and proteins

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