U.S. flag

An official website of the United States government

Format

Send to:

Choose Destination

Severe X-linked myotubular myopathy(CNMX)

MedGen UID:
98374
Concept ID:
C0410203
Congenital Abnormality
Synonyms: CNMX; MYOTUBULAR MYOPATHY 1; Myotubular myopathy, X-linked; X-linked centronuclear myopathy
SNOMED CT: Severe X-linked myotubular myopathy (46804001); X-linked centronuclear myopathy (46804001)
Modes of inheritance:
X-linked recessive inheritance
MedGen UID:
375779
Concept ID:
C1845977
Finding
Source: Orphanet
A mode of inheritance that is observed for recessive traits related to a gene encoded on the X chromosome. In the context of medical genetics, X-linked recessive disorders manifest in males (who have one copy of the X chromosome and are thus hemizygotes), but generally not in female heterozygotes who have one mutant and one normal allele.
 
Gene (location): MTM1 (Xq28)
 
Monarch Initiative: MONDO:0010683
OMIM®: 310400
Orphanet: ORPHA596

Disease characteristics

Excerpted from the GeneReview: X-Linked Myotubular Myopathy
X-linked myotubular myopathy (X-MTM), also known as myotubular myopathy (MTM), is characterized by muscle weakness that ranges from severe to mild. Approximately 80% of affected males present with severe (classic) X-MTM characterized by polyhydramnios, decreased fetal movement, and neonatal weakness, hypotonia, and respiratory failure. Motor milestones are significantly delayed and most individuals fail to achieve independent ambulation. Weakness is profound and often involves facial and extraocular muscles. Respiratory failure is nearly uniform, with most individuals requiring 24-hour ventilatory assistance. It is estimated that at least 25% of boys with severe X-MTM die in the first year of life, and those who survive rarely live into adulthood. Males with mild or moderate X-MTM (~20%) achieve motor milestones more quickly than males with the severe form; many ambulate independently, and may live into adulthood. Most require gastrostomy tubes and/or ventilator support. In all subtypes of X-MTM, the muscle disease is not obviously progressive. Female carriers of X-MTM are generally asymptomatic, although manifesting heterozygotes are increasingly being identified. In affected females, symptoms range from severe, generalized weakness presenting in childhood, with infantile onset similar to affected male patients, to mild (often asymmetric) weakness manifesting in adulthood. Affected adult females may experience progressive respiratory decline and ultimately require ventilatory support. [from GeneReviews]
Authors:
James J Dowling  |  Michael W Lawlor  |  Soma Das   view full author information

Additional description

From MedlinePlus Genetics
X-linked myotubular myopathy is a condition that primarily affects muscles used for movement (skeletal muscles) and occurs almost exclusively in males. People with this condition have muscle weakness (myopathy) and decreased muscle tone (hypotonia) that are usually evident at birth. When viewed under a microscope, the muscle fibers of affected individuals are typically small and underdeveloped.

The muscle problems in X-linked myotubular myopathy impair the development of motor skills such as sitting, standing, and walking. Affected infants may also have difficulties with feeding due to muscle weakness. Individuals with this condition often do not have the muscle strength to breathe regularly on their own and must be supported with a machine to help them get enough oxygen (mechanical ventilation). Some affected individuals need breathing assistance only periodically, typically during sleep, while others require it continuously. People with X-linked myotubular myopathy may also have weakness in the muscles that control eye movement (ophthalmoplegia), weakness in other muscles of the face, and absent reflexes (areflexia).

In X-linked myotubular myopathy, muscle weakness often disrupts normal bone development and can lead to fragile bones, an abnormal curvature of the spine (scoliosis), and joint deformities (contractures) of the hips and knees. People with X-linked myotubular myopathy may have a large head with a narrow and elongated face and a high, arched roof of the mouth (palate). They may also have recurrent ear and respiratory infections, seizures, or liver disease. Some affected individuals develop a serious liver condition called peliosis hepatitis, which can cause life-threatening bleeding (hemorrhage).

Because of their severe breathing problems, individuals with X-linked myotubular myopathy usually survive only into early childhood; however, some people with this condition have lived into adulthood.

X-linked myotubular myopathy is the most severe condition in a group of disorders called centronuclear myopathy. In centronuclear myopathy, the nucleus is found at the center of many rod-shaped muscle cells instead of at either end, where it is normally located.  https://medlineplus.gov/genetics/condition/x-linked-myotubular-myopathy

Clinical features

From HPO
Cryptorchidism
MedGen UID:
8192
Concept ID:
C0010417
Congenital Abnormality
Cryptorchidism, or failure of testicular descent, is a common human congenital abnormality with a multifactorial etiology that likely reflects the involvement of endocrine, environmental, and hereditary factors. Cryptorchidism can result in infertility and increases risk for testicular tumors. Testicular descent from abdomen to scrotum occurs in 2 distinct phases: the transabdominal phase and the inguinoscrotal phase (summary by Gorlov et al., 2002).
Arachnodactyly
MedGen UID:
2047
Concept ID:
C0003706
Congenital Abnormality
Abnormally long and slender fingers ("spider fingers").
Slender toe
MedGen UID:
866814
Concept ID:
C4021168
Finding
Toes that are disproportionately narrow (reduced girth) for the hand/foot size or build of the individual.
Birth length greater than 97th percentile
MedGen UID:
326443
Concept ID:
C1839271
Finding
Tube feeding
MedGen UID:
8641
Concept ID:
C0014327
Therapeutic or Preventive Procedure
Feeding problem necessitating food and nutrient delivery via a tube.
Congenital hypertrophic pyloric stenosis
MedGen UID:
196010
Concept ID:
C0700639
Congenital Abnormality
Pyloric stenosis, also known as infantile hypertrophic pyloric stenosis, is an uncommon condition in infants characterized by abnormal thickening of the pylorus muscles in the stomach leading to gastric outlet obstruction. Clinically infants are well at birth. Then, at 3 to 6 weeks of age, the infants present with projectile vomiting, potentially leading to dehydration and weight loss.
Hydrocephalus
MedGen UID:
9335
Concept ID:
C0020255
Disease or Syndrome
Hydrocephalus is an active distension of the ventricular system of the brain resulting from inadequate passage of CSF from its point of production within the cerebral ventricles to its point of absorption into the systemic circulation.
Hypokinesia
MedGen UID:
39223
Concept ID:
C0086439
Finding
Abnormally diminished motor activity. In contrast to paralysis, hypokinesia is not characterized by a lack of motor strength, but rather by a poverty of movement. The typical habitual movements (e.g., folding the arms, crossing the legs) are reduced in frequency.
Areflexia
MedGen UID:
115943
Concept ID:
C0234146
Finding
Absence of neurologic reflexes such as the knee-jerk reaction.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Dandy-Walker syndrome
MedGen UID:
4150
Concept ID:
C0010964
Disease or Syndrome
Dandy-Walker malformation is defined by hypoplasia and upward rotation of the cerebellar vermis and cystic dilation of the fourth ventricle. Affected individuals often have motor deficits such as delayed motor development, hypotonia, and ataxia; about half have mental retardation and some have hydrocephalus. DWM is a heterogeneous disorder. The low empiric recurrence risk of approximately 1 to 2% for nonsyndromic DWM suggests that mendelian inheritance is unlikely (summary by Murray et al., 1985).
Diaphragmatic eventration
MedGen UID:
8359
Concept ID:
C0011981
Congenital Abnormality
A congenital failure of muscular development of part or all of one or both hemidiaphragms, resulting in superior displacement of abdominal viscera and altered lung development.
Dolichocephaly
MedGen UID:
65142
Concept ID:
C0221358
Congenital Abnormality
An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture.
Neck muscle weakness
MedGen UID:
66808
Concept ID:
C0240479
Finding
Decreased strength of the neck musculature.
Flexion contracture
MedGen UID:
83069
Concept ID:
C0333068
Anatomical Abnormality
A flexion contracture is a bent (flexed) joint that cannot be straightened actively or passively. It is thus a chronic loss of joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevents normal movement of joints.
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Generalized muscle weakness
MedGen UID:
155433
Concept ID:
C0746674
Sign or Symptom
Generalized weakness or decreased strength of the muscles, affecting both distal and proximal musculature.
Severe muscular hypotonia
MedGen UID:
326544
Concept ID:
C1839630
Finding
A severe degree of muscular hypotonia characterized by markedly reduced muscle tone.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Neonatal hypotonia
MedGen UID:
412209
Concept ID:
C2267233
Disease or Syndrome
Muscular hypotonia (abnormally low muscle tone) manifesting in the neonatal period.
Respiratory failure requiring assisted ventilation
MedGen UID:
870821
Concept ID:
C4025279
Finding
A state of respiratory distress that requires a life saving intervention in the form of gaining airway access and instituting positive pressure ventilation.
Neonatal respiratory distress
MedGen UID:
924182
Concept ID:
C4281993
Finding
Respiratory difficulty as newborn.
Elevated hepatic transaminase
MedGen UID:
338525
Concept ID:
C1848701
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Dental malocclusion
MedGen UID:
9869
Concept ID:
C0024636
Anatomical Abnormality
Dental malocclusion refers to an abnormality of the occlusion, or alignment, of the teeth and the way the upper and lower teeth fit together, resulting in overcrowding of teeth or in abnormal bite patterns.
High forehead
MedGen UID:
65991
Concept ID:
C0239676
Finding
An abnormally increased height of the forehead.
High palate
MedGen UID:
66814
Concept ID:
C0240635
Congenital Abnormality
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Long face
MedGen UID:
324419
Concept ID:
C1836047
Finding
Facial height (length) is more than 2 standard deviations above the mean (objective); or, an apparent increase in the height (length) of the face (subjective).
Narrow face
MedGen UID:
373334
Concept ID:
C1837463
Finding
Bizygomatic (upper face) and bigonial (lower face) width are both more than 2 standard deviations below the mean (objective); or, an apparent reduction in the width of the upper and lower face (subjective).
Caesarian section
MedGen UID:
863
Concept ID:
C0007876
Therapeutic or Preventive Procedure
Delivery of a fetus through surgical incisions made through the abdominal wall (laparotomy) and the uterine wall (hysterotomy).
Polyhydramnios
MedGen UID:
6936
Concept ID:
C0020224
Pathologic Function
The presence of excess amniotic fluid in the uterus during pregnancy.
Premature birth
MedGen UID:
57721
Concept ID:
C0151526
Pathologic Function
The birth of a baby of less than 37 weeks of gestational age.
Decreased fetal movement
MedGen UID:
68618
Concept ID:
C0235659
Finding
An abnormal reduction in quantity or strength of fetal movements.
Low 1-minute APGAR score
MedGen UID:
1369505
Concept ID:
C4476848
Finding
Low 5-minute APGAR score
MedGen UID:
1370671
Concept ID:
C4476849
Finding
External ophthalmoplegia
MedGen UID:
57662
Concept ID:
C0162292
Disease or Syndrome
Paralysis of the external ocular muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
Follow this link to review classifications for Severe X-linked myotubular myopathy in Orphanet.

Professional guidelines

PubMed

Gómez-Oca R, Cowling BS, Laporte J
Int J Mol Sci 2021 Oct 21;22(21) doi: 10.3390/ijms222111377. PMID: 34768808Free PMC Article
Natera-de Benito D, Ortez C, Jou C, Jimenez-Mallebrera C, Codina A, Carrera-García L, Expósito-Escudero J, Cesar S, Martorell L, Gallano P, Gonzalez-Quereda L, Cuadras D, Colomer J, Yubero D, Palau F, Nascimento A
Pediatr Neurol 2021 Feb;115:50-65. Epub 2020 Nov 5 doi: 10.1016/j.pediatrneurol.2020.11.002. PMID: 33333461
Morin G, Biancalana V, Echaniz-Laguna A, Noury JB, Lornage X, Moggio M, Ripolone M, Violano R, Marcorelles P, Maréchal D, Renaud F, Maurage CA, Tard C, Cuisset JM, Laporte J, Böhm J
Hum Mutat 2020 Jan;41(1):17-37. Epub 2019 Sep 15 doi: 10.1002/humu.23899. PMID: 31448844

Curated

Biancalana V, Beggs AH, Das S, Jungbluth H, Kress W, Nishino I, North K, Romero NB, Laporte J
Eur J Hum Genet 2012 Oct;20(10) Epub 2012 May 23 doi: 10.1038/ejhg.2012.91. PMID: 22617344Free PMC Article

Recent clinical studies

Etiology

Vandersmissen I, Biancalana V, Servais L, Dowling JJ, Vander Stichele G, Van Rooijen S, Thielemans L
Neuromuscul Disord 2018 Sep;28(9):766-777. Epub 2018 Jul 1 doi: 10.1016/j.nmd.2018.06.012. PMID: 30122513

Diagnosis

Bryen SJ, Oates EC, Evesson FJ, Lu JK, Waddell LB, Joshi H, Ryan MM, Cummings BB, McLean CA, MacArthur DG, Kornberg AJ, Cooper ST
Eur J Hum Genet 2021 Jan;29(1):61-66. Epub 2020 Aug 29 doi: 10.1038/s41431-020-00715-7. PMID: 32862205Free PMC Article

Prognosis

Vandersmissen I, Biancalana V, Servais L, Dowling JJ, Vander Stichele G, Van Rooijen S, Thielemans L
Neuromuscul Disord 2018 Sep;28(9):766-777. Epub 2018 Jul 1 doi: 10.1016/j.nmd.2018.06.012. PMID: 30122513
Tyson RW, Ringel SP, Manchester DK, Shikes RH, Goodman SI
Pediatr Pathol 1992 Jul-Aug;12(4):535-43. doi: 10.3109/15513819209024203. PMID: 1409152

Supplemental Content

Table of contents

    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.
    • Bookshelf
      See practice and clinical guidelines in NCBI Bookshelf. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • EuroGenetest, 2012
      Clinical utility gene card for: Centronuclear and myotubular myopathies.

    Recent activity

    Your browsing activity is empty.

    Activity recording is turned off.

    Turn recording back on

    See more...