Facioscapulohumeral muscular dystrophy
| Classification according to ICD-10 | |
|---|---|
| G71.0 | Muscular dystrophy |
| ICD-10 online (WHO version 2019) | |
The facioscapulohumeral muscular dystrophy (FSHMD, FSHD, muscular dystrophy Landouzy-Dejerine or Landouzy-Dejerine syndrome ) is a muscle disease (myopathy). The Latin name of the disease is derived from the muscle groups mainly affected: the facial muscles (- fazio ), the shoulder girdle muscles (- skapulo ) and the upper arm muscles (- humeral ).
The disease is caused by a change in the genetic material (genome) and is inherited as an autosomal dominant trait.
In most cases, the disease begins in adolescence or young adulthood. Compared to many other muscular dystrophies , the course is relatively mild in most cases. However, around 20 percent of patients will need a wheelchair to cope with longer walking distances. In most cases, the suspicion of FSHD can already be made based on the typical distribution pattern in connection with the symptoms. The diagnosis is confirmed with the help of a molecular genetic examination . The main focus of treatment is regular physiotherapy . A cure is not possible.
Medical history
The first description of the disease in 1868 goes back to Guillaume-Benjamin Duchenne , a French physiologist. The disease was named after the French neurologists Louis Théophile Joseph Landouzy and Joseph Jules Dejerine , who described the clinical picture in great detail in 1884.
frequency
The frequency (prevalence) of FSHD is estimated at one patient per 20,000 population. This makes it the third most common hereditary muscle disease after the progressive muscular dystrophy type Duchenne and the myotonic muscular dystrophy Curschmann-Steinert .
Genetic cause
Depending on the underlying mutation, the following forms can be distinguished:
- Type 1 (FSHD1) “classic form”, mutations in the DUX4 gene on chromosome 4 locus q35.2
- Type 2 (FSHD2), mutations in the SMCHD1 gene on chromosome 18 at p11.32
FSHD is associated with a partial deletion of the polymorphic segment D4Z4 on chromosome 4 , which codes for the double homeobox protein DUX4 . The result is the translation of splice variants of DUX4 that differ from the normal DUX4. These differences are particularly noticeable in the fact that DUX4 is now no longer expressed in myoblasts or in a lower amount . DUX4 is a transcription factor that normally stimulates the expression of several proteins in myoblasts that are essential for the differentiation of the myoblasts into adult muscle cells, including the myosin heavy chain . So no muscles can grow from the muscle precursor cells.
Clinical picture
Both the beginning of the symptoms - the manifestation of the disease - and the severity of the symptoms are very variable overall. The disease can manifest itself at almost any age. However, it typically begins in the first or second decade of life. In about one fifth, the onset of the disease occurs in infancy. This is often associated with a more severe and faster course of the disease. The severity of the symptoms ranges from mild facial paralysis to severe paralysis of almost all of the muscles.
The disease usually first shows itself with weakness of the facial muscles (facial muscles). The muscles are often affected asymmetrically, especially at the beginning of the disease. Typically, patients suffer from paralysis of the eye ring muscles from decreased eyelid closure (lagophthalmos), which in the early stages can lead to patients sleeping with their eyes open. During the physical examination, the incomplete eyelid closure can initially be detected as a ciliary sign (Signe de cils), which means that when the eyes are squeezed shut, in contrast to healthy people, the eyelashes remain visible. Another characteristic is that the affected patients cannot whistle or drink through a straw (due to paralysis of the orbicularis oris muscle ). A frequently encountered hypertrophy of the orbicularis oris muscle leads to a so-called tapir or pout .
In addition to the affected facial muscles, weakness of the shoulder girdle muscles usually also occurs early on. When the patient leans against a wall with his arms stretched forward, the shoulder blades protrude from the atrophy of the shoulder girdle muscles. A protruding shoulder blade is called a scapula alata . Another characteristic is a horizontal or laterally sloping position of the collarbones. Atrophy of the chest muscles ( muscles pectorales majores and muscles pectorales minores ) is also typical, causing the chest to flatten.
Contrary to what the name of the disease suggests, the muscles of the foot lifters are usually affected relatively early on. Due to the weakness of the dorsiflexion , the affected patients show a typical gait pattern, which is known as a stepper gait . The upper arm muscles are affected relatively late. In addition, the pelvic girdle muscles can also be affected, usually in later stages of the disease.
In advanced stages, patients have difficulty climbing stairs, working over their heads, and straightening up from a lying position. In an average of 20 percent of all patients, a wheelchair is necessary to move around.
In addition to the skeletal muscles, many patients experience hearing loss , which in most cases is only very slight and is therefore often not even noticed by the patient. If FSHD manifests itself in infancy or in toddlerhood, the hearing loss can occasionally extend to deafness. In addition, an abnormality of the retinal vessels is often detectable, but this is rarely noticeable clinically. In rare cases, however, a so-called Coats syndrome occurs, damage to the retina (retinopathy) with telangiectasia , which can lead to blindness. Involvement of the heart muscles is also rare and rather atypical compared to other muscle diseases . In individual cases, cardiac arrhythmias such as atrial flutter and atrial fibrillation and conduction disorders such as disorders of the sinus node can occur.
See also
literature
- F. Jerusalem, S. Zierz: Muscle Diseases . 3. Edition. Thieme-Verlag, 2003, ISBN 3-13-567803-2 , pp. 103-106 ff.
- J. Sieb, B. Cabinet: Neuromuscular Diseases. 1st edition. Kohlhammer Verlag, 2009, ISBN 978-3-17-018381-0 , pp. 93-104.
Web links
Individual evidence
- ↑ GBA Duchenne: Recherches sur la paralysie musculaire pseudo-hypertrophique, ou paraly- sie myo-sclérosique. In: Arch Gén Méd. 6 ser. 1868; 6 ser, 11, pp. 5-25, 179-209, 305-321, 421-443, 552-588.
- ↑ a b M. Krasnianski et al .: Facioscapulohumeral muscular dystrophy. The spectrum of clinical manifestations and molecular genetic changes. In: Neurologist. 2003 Feb; 74 (2), pp. 151-158. PMID 12596016
- ↑ L. Landouzy, J. Dejerine: De la myopathie atrophique progressive (myopathie héréditaire, débutant d'ordinaire dans l'enfance par la face, sans altération du système nerveux). In: Comptes rendus de l'Académie des sciences. Paris 1884, 98, pp. 53–55 and in detail in Révué de Médédine 1885; 5: 81-117
- ↑ PW Lunt et al .: Genetic counseling in facioscapulohumeral muscular dystrophy. In: J Med Genet. 1991 Oct; 28 (10), pp. 655-664. PMID 1941962 .
- ↑ Facio-scapulo-humeral muscular dystrophy. In: Orphanet (Rare Disease Database).
- ↑ Facioscapulohumeral muscular dystrophy 1. In: Online Mendelian Inheritance in Man . (English)
- ↑ Facioscapulohumeral muscular dystrophy 2. In: Online Mendelian Inheritance in Man . (English)
- ↑ DUX4. In: Online Mendelian Inheritance in Man . (English)