Format

Send to:

Choose Destination

Hereditary myopathy with early respiratory failure(MFM9)

MedGen UID:
350930
Concept ID:
C1863599
Disease or Syndrome
Synonyms: EDSTROM MYOPATHY; Hereditary Myopathy with Early Respiratory Failure (HMERF); MFM9; MYOPATHY, DISTAL, WITH EARLY RESPIRATORY FAILURE, AUTOSOMAL DOMINANT; MYOPATHY, MYOFIBRILLAR, 9, WITH EARLY RESPIRATORY FAILURE; MYOPATHY, PROXIMAL, WITH EARLY RESPIRATORY MUSCLE INVOLVEMENT
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM, Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
SNOMED CT: MPRM - myopathy, proximal, with early respiratory muscle involvement (702373006); HMERF - hereditary myopathy with early respiratory failure (702373006); Hereditary myopathy with early respiratory failure (702373006); Hereditary proximal myopathy with early respiratory failure (702373006); Edstrom myopathy (702373006)
 
Gene (location): TTN (2q31.2)
OMIM®: 603689
Orphanet: ORPHA178464

Disease characteristics

Hereditary myopathy with early respiratory failure (HMERF) is a slowly progressive myopathy that typically begins in the third to fifth decades of life. The usual presenting findings are gait disturbance relating to distal leg weakness or nocturnal respiratory symptoms due to respiratory muscle weakness. Weakness eventually generalizes and affects both proximal and distal muscles. Most affected individuals require walking aids within a few years of onset; some progress to wheelchair dependence and require nocturnal noninvasive ventilatory support. The disease course varies even among individuals within the same family: some remain ambulant until their 70s whereas others may require ventilator support in their 40s. [from GeneReviews]
Authors:
Gerald Pfeffer  |  Patrick F Chinnery   view full author information

Additional descriptions

From OMIM
Myofibrillar myopathy-9 with early respiratory failure (MFM9) is an autosomal dominant muscle disorder characterized by adult onset of slowly progressive muscle weakness with diaphragmatic involvement causing respiratory insufficiency. Patients present between 20 and 70 years of age with distal or proximal muscle weakness, mainly affecting the lower limbs with foot drop or difficulty walking. The age at onset is highly variable, even within families. Nearly all patients eventually develop significant proximal and distal weakness, as well as respiratory insufficiency requiring nocturnal ventilation. Additional, more variable features may include axial weakness, neck muscle weakness, and rarely, cardiac involvement. Muscle biopsy shows myopathic or dystrophic changes with fiber splitting, eosinophilic cytoplasmic inclusions consistent with myofibrillar myopathy, rimmed vacuoles, and increased connective or fatty tissue (summary by Pfeffer et al., 2014). For a phenotypic description and a discussion of genetic heterogeneity of myofibrillar myopathy (MFM), see MFM1 (601419).  http://www.omim.org/entry/603689
From GHR
Hereditary myopathy with early respiratory failure (HMERF) is an inherited disease that affects muscles used for movement (skeletal muscles) and muscles that are needed for breathing (respiratory muscles).The major signs and symptoms of HMERF usually appear in adulthood, often in the mid-thirties. Among the earliest signs of the condition are breathing problems and difficulty walking. Weakness of the respiratory muscles, particularly the diaphragm (the muscle that separates the organs in the abdomen from those in the chest), causes breathing problems. This weakness worsens over time and can lead to life-threatening respiratory failure. Some affected individuals have weakness of muscles of the lower leg and foot, which makes it difficult to lift the toes while walking, a condition known as foot drop. Other muscles that become weak in people with HMERF include those of the hips, thighs, upper arms, and neck.When viewed under a microscope, muscle fibers from affected individuals contain abnormal structures called cytoplasmic bodies. In many cases, the cytoplasmic bodies are arranged side-by-side in a ring inside the muscle fiber, resembling a necklace (necklace cytoplasmic bodies).  https://ghr.nlm.nih.gov/condition/hereditary-myopathy-with-early-respiratory-failure

Clinical features

Diaphragmatic weakness
MedGen UID:
101067
Concept ID:
C0521532
Finding
A decrease in the strength of the diaphragm.
Proximal muscle weakness
MedGen UID:
325534
Concept ID:
C1838869
Sign or Symptom
A lack of strength of the proximal muscles.
Neck flexor weakness
MedGen UID:
334801
Concept ID:
C1843637
Finding
Weakness of the muscles involved in neck flexion (sternocleidomastoid, longus capitus, longus colli, and scalenus anterior).
Foot dorsiflexor weakness
MedGen UID:
356163
Concept ID:
C1866141
Finding
Weakness of the muscles responsible for dorsiflexion of the foot, that is, of the movement of the toes towards the shin. The foot dorsiflexors include the tibialis anterior, the extensor hallucis longus, the extensor digitorum longus, and the peroneus tertius muscles.

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  
  • CROGVHereditary myopathy with early respiratory failure
Follow this link to review classifications for Hereditary myopathy with early respiratory failure in Orphanet.

Recent clinical studies

Etiology

Steele HE, Harris E, Barresi R, Marsh J, Beattie A, Bourke JP, Straub V, Chinnery PF
Neurology 2016 Sep 6;87(10):1031-5. Epub 2016 Aug 10 doi: 10.1212/WNL.0000000000003064. PMID: 27511179Free PMC Article
Pfeffer G, Sambuughin N, Olivé M, Tyndel F, Toro C, Goldfarb LG, Chinnery PF
Neuromuscul Disord 2014 Mar;24(3):241-4. Epub 2013 Dec 11 doi: 10.1016/j.nmd.2013.12.001. PMID: 24444549Free PMC Article
Izumi R, Niihori T, Aoki Y, Suzuki N, Kato M, Warita H, Takahashi T, Tateyama M, Nagashima T, Funayama R, Abe K, Nakayama K, Aoki M, Matsubara Y
J Hum Genet 2013 May;58(5):259-66. Epub 2013 Feb 28 doi: 10.1038/jhg.2013.9. PMID: 23446887
Ohlsson M, Hedberg C, Brådvik B, Lindberg C, Tajsharghi H, Danielsson O, Melberg A, Udd B, Martinsson T, Oldfors A
Brain 2012 Jun;135(Pt 6):1682-94. Epub 2012 May 9 doi: 10.1093/brain/aws103. PMID: 22577218
Pfeffer G, Elliott HR, Griffin H, Barresi R, Miller J, Marsh J, Evilä A, Vihola A, Hackman P, Straub V, Dick DJ, Horvath R, Santibanez-Koref M, Udd B, Chinnery PF
Brain 2012 Jun;135(Pt 6):1695-713. Epub 2012 May 9 doi: 10.1093/brain/aws102. PMID: 22577215Free PMC Article

Diagnosis

Uruha A, Hayashi YK, Oya Y, Mori-Yoshimura M, Kanai M, Murata M, Kawamura M, Ogata K, Matsumura T, Suzuki S, Takahashi Y, Kondo T, Kawarabayashi T, Ishii Y, Kokubun N, Yokoi S, Yasuda R, Kira J, Mitsuhashi S, Noguchi S, Nonaka I, Nishino I
J Neurol Neurosurg Psychiatry 2015 May;86(5):483-9. Epub 2014 Sep 24 doi: 10.1136/jnnp-2014-309009. PMID: 25253871
Palmio J, Evilä A, Chapon F, Tasca G, Xiang F, Brådvik B, Eymard B, Echaniz-Laguna A, Laporte J, Kärppä M, Mahjneh I, Quinlivan R, Laforêt P, Damian M, Berardo A, Taratuto AL, Bueri JA, Tommiska J, Raivio T, Tuerk M, Gölitz P, Chevessier F, Sewry C, Norwood F, Hedberg C, Schröder R, Edström L, Oldfors A, Hackman P, Udd B
J Neurol Neurosurg Psychiatry 2014 Mar;85(3):345-53. Epub 2013 Apr 19 doi: 10.1136/jnnp-2013-304965. PMID: 23606733
Toro C, Olivé M, Dalakas MC, Sivakumar K, Bilbao JM, Tyndel F, Vidal N, Farrero E, Sambuughin N, Goldfarb LG
BMC Neurol 2013 Mar 20;13:29. doi: 10.1186/1471-2377-13-29. PMID: 23514108Free PMC Article
Izumi R, Niihori T, Aoki Y, Suzuki N, Kato M, Warita H, Takahashi T, Tateyama M, Nagashima T, Funayama R, Abe K, Nakayama K, Aoki M, Matsubara Y
J Hum Genet 2013 May;58(5):259-66. Epub 2013 Feb 28 doi: 10.1038/jhg.2013.9. PMID: 23446887
Tasca G, Mirabella M, Broccolini A, Monforte M, Sabatelli M, Biscione GL, Piluso G, Gualandi F, Tonali PA, Udd B, Ricci E
Neuromuscul Disord 2010 Nov;20(11):730-4. Epub 2010 Aug 13 doi: 10.1016/j.nmd.2010.07.269. PMID: 20708934

Prognosis

Uruha A, Hayashi YK, Oya Y, Mori-Yoshimura M, Kanai M, Murata M, Kawamura M, Ogata K, Matsumura T, Suzuki S, Takahashi Y, Kondo T, Kawarabayashi T, Ishii Y, Kokubun N, Yokoi S, Yasuda R, Kira J, Mitsuhashi S, Noguchi S, Nonaka I, Nishino I
J Neurol Neurosurg Psychiatry 2015 May;86(5):483-9. Epub 2014 Sep 24 doi: 10.1136/jnnp-2014-309009. PMID: 25253871
Izumi R, Niihori T, Aoki Y, Suzuki N, Kato M, Warita H, Takahashi T, Tateyama M, Nagashima T, Funayama R, Abe K, Nakayama K, Aoki M, Matsubara Y
J Hum Genet 2013 May;58(5):259-66. Epub 2013 Feb 28 doi: 10.1038/jhg.2013.9. PMID: 23446887
Ohlsson M, Hedberg C, Brådvik B, Lindberg C, Tajsharghi H, Danielsson O, Melberg A, Udd B, Martinsson T, Oldfors A
Brain 2012 Jun;135(Pt 6):1682-94. Epub 2012 May 9 doi: 10.1093/brain/aws103. PMID: 22577218

Clinical prediction guides

Uruha A, Hayashi YK, Oya Y, Mori-Yoshimura M, Kanai M, Murata M, Kawamura M, Ogata K, Matsumura T, Suzuki S, Takahashi Y, Kondo T, Kawarabayashi T, Ishii Y, Kokubun N, Yokoi S, Yasuda R, Kira J, Mitsuhashi S, Noguchi S, Nonaka I, Nishino I
J Neurol Neurosurg Psychiatry 2015 May;86(5):483-9. Epub 2014 Sep 24 doi: 10.1136/jnnp-2014-309009. PMID: 25253871
Palmio J, Evilä A, Chapon F, Tasca G, Xiang F, Brådvik B, Eymard B, Echaniz-Laguna A, Laporte J, Kärppä M, Mahjneh I, Quinlivan R, Laforêt P, Damian M, Berardo A, Taratuto AL, Bueri JA, Tommiska J, Raivio T, Tuerk M, Gölitz P, Chevessier F, Sewry C, Norwood F, Hedberg C, Schröder R, Edström L, Oldfors A, Hackman P, Udd B
J Neurol Neurosurg Psychiatry 2014 Mar;85(3):345-53. Epub 2013 Apr 19 doi: 10.1136/jnnp-2013-304965. PMID: 23606733

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center