Emery tripod muscular dystrophy

Classification according to ICD-10
G71.0	Muscular dystrophy
ICD-10 online (WHO version 2019)

The Emery-Dreifuss Muscular Dystrophy ( EDMD ) in 1962 for the first time as an independent muscular dystrophy described.

Synonym: Hauptmann-Thannhauser syndrome .

There are currently two known hereditary forms of the disease. On the one hand, it can occur through the mutation of the 34 kDa core protein Emerin (gene locus Xq28) (X-linked EDMD). Furthermore, various mutations of the LMNA gene (gene locus 1q21), which codes for the core structural proteins Lamin A / C , can initiate the autosomal dominant form of the disease (AD-EDMD).

Symptoms

Symptoms of the disease are slowly emerging in young patients. The disease can be characterized by three different abnormalities:

• Most patients show a shortening of the Achilles tendons and elbow muscles. It is usually not possible for those affected to straighten their arms or legs.
• Many patients show slow muscle wear and tear, followed by muscle weakness.
• Dilated cardiac vessels, especially in the right atrium of the heart, are the result of EDMD.

diagnosis

When EDMD is diagnosed, the first sign of disease is an increase in serum creatine kinase levels. Electromyography can also show changes in muscle activity. It is important to diagnose cardiac involvement with EKG, long-term EKG, echocardiography and, if necessary, further examinations, since cardiac arrhythmias represent a potentially fatal complication of the disease. Muscle histology usually reveals muscle necrosis and phagocytosis of necrotic muscle cells.

Molecular pathology

The gene locus for X-linked EDMD is Xp28. The STA gene is 2100 base pairs long and contains six exons . This creates a 34 kDa protein called emerin, which is expressed in the inner nuclear membrane of skeletal, heart and smooth muscle. Mutation databases have so far recorded several hundred mutations of the STA gene. All mutations in the STA gene result in a complete loss of emerin. The connection between the deletion of the core protein Emerin and the resulting muscular dystrophy has not yet been clarified.

The gene for AD-EDMD was identified at locus 1q21. Using the alternative splice process, this gene codes for core lamines A and C, which are both core structural proteins. They interact with chromatin as well as with different IM proteins like MAN1, LAPs or Emerin. In addition to AD-EDMD, limb gurtle muscular dystrophy also shows a mutation in the LMNA gene.

So far, the connection between the mutation of the LMNA gene and the resulting muscular dystrophy was unclear and was based only on speculation. Misteli et al. Showed in a publication (2009) that a mislocalization of the nucleus of the muscle cells leads to an incorrect structure of the motor end plate . The cytoskeleton in connection with Lamin A, Nesprin- 1 and SUN proteins plays a major role in positioning the specialized nuclei on the motor endplate of the muscle . If one of these proteins is expressed incorrectly or not at all, the synaptic nuclei at the postsynapse of the motor endplate are mislocated. As a result, the muscle cannot be properly innervated.

therapy

Affected patients must first adjust their lifestyle. This includes avoiding sporting activities that can cause deformations in muscles. Furthermore, the patients are treated with physiotherapy .

The most important aspect, however, is the early detection of the disease in order to be able to prevent heart defects. It is also useful to take a family history to identify possible genetic predispositions.

Some approaches, which are not yet in the clinical phase, deal with gene therapy and the use of adenoviral vectors to smuggle in emerin equivalents.

See also

• Davidenkow Syndrome
• Mandibuloacral dysplasia

swell

• AE Emery, FE Dreifuss: Unusual type of benign x-linked muscular dystrophy. In: J Neurol Neurosurg Psychiatry. 1966 Aug; 29 (4), pp. 338-342. PMID 5969090

• JA Ellis: Emery-Dreifuss muscular dystrophy at the nuclear envelope: 10 years on. In: Cell Mol Life Sci. 2006 Dec; 63 (23), pp. 2702-2709. Review. PMID 17013557

• A. Méjat et al .: Lamin A / C-mediated neuromuscular junction defects in Emery-Dreifuss muscular dystrophy. In: J Cell Biol . 2009 Jan 12; 184 (1), pp. 31-44. Epub 2009 Jan 5. PMID 19124654

Web links

• Emery-Dreifuss syndrome at www.whonamedit.com

Individual evidence

1. ^ Emery Dreifuss Muscular Dystrophy.  In: Online Mendelian Inheritance in Man . (English)

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