Landouzy-Dejerine Dystrophy (Facioscapulohumeral Muscular Dystrophy)

Risk

• Prevalence estimated to be 1:20,000

• Affects equally males and females

• Third most common familial myopathy after myotonic dystrophy and Duchenne muscular dystrophy

Perioperative Risks

• No greater risk of malignant hyperthermia than normal population.

• Possible risk of acute rhabdomyolysis if succinylcholine and/or a halogenated agent is used. However, the dystrophin-glycoprotein complex is not involved in Landouzy-Dejerine dystrophy, and no case of anesthesia-induced rhabdomyolysis has been reported so far.

Worry About

• Muscle weakness

• Perioperative respiratory complications

• Supraventricular paroxysmal tachycardia

Overview

• Muscular dystrophies are a heterogeneous group of genetic muscle disorders leading to progressive weakness and muscle wasting. They were grouped together based on a common histologic picture: variations in fiber size and areas of muscle necrosis progressively replaced with fat or connective tissue. They are classified based on three phenotypic considerations: predominant distribution of affected muscles, whether facial muscles are affected or not, and mode of inheritance.

• Its clinical presentation varies widely. Approximately 30% of people with a mutation do not present any clinical sign; this could be due to mosaicism. For those presenting with clinical signs, the distribution of muscle weakness varies widely. Two main clinical forms are described below.

• Congenital or infantile form: Facial muscles are affected before 5 years of age, and the muscles of the shoulder and hip girdle around 10 years: muscular involvement is bilateral and symmetric, resulting in apparent facial diplegia and poor expression of emotions. Sensorineural hearing loss is common. Hyperlordosis and scoliosis appear in late childhood and adolescence.

• Usual form: Muscular involvement is asymmetric and starts during adolescence. The first signs affect the face and the shoulder girdle: difficulties drinking with a straw, pursing the lips or whistling, inability to close the eyes (risk of keratitis during sleep), and protruding lips (tapir mouth). All muscles of the shoulder are affected but the deltoid is usually spared, which results in a preserved deltoid bulk despite surrounding muscles atrophy: this produces scapular winging when the arms are abducted. The foot dorsiflexors and the hip are affected later and result in stepping and difficult walking (need for a cane). Weakness of abdominal wall muscles is frequent and can result in some abdominal wall protrusion. The following signs are also frequent: (1) early onset and bilateral sensorineural hearing loss, which varies from mild to moderate; (2) bilateral retinal exudative telangiectasia, called Coats disease, with marked tortuosity of retinal arterioles. Respiratory muscle involvement is usually mild, but severe cases can result in early onset and progression of severe restrictive pulmonary dysfunction, and cor pulmonale. A few cases of hypertrophic cardiomyopathy and cardiac arrhythmias (mainly supraventricular paroxysmal tachycardia) have been observed.

• The evolution is slow and progressive: 20% become wheelchair bound, and less than 5% of pts end up with some form of ventilation support during sleep.

• Paraclinical examinations: CPK: Normal or mildly elevated (<1500 UI/L); RFT: Restrictive pattern in severe forms; EMG: Myopathic changes.

Etiology

There are currently two different known genetic causes of LDD:

• Type 1 [OMIM 158 900] is the most frequent (85% of cases); it is caused by a shortening of the D4Z4 zone in the subtelomeric region of chromosome 4q (4q35.2). This zone is usually hypermethylated and includes tandem repeats of a fragment containing a DUX4 (nuclear protein) open reading frame. The normal number of these repeats varies between 11 and 100: it is lower than 10 in case of myopathy but results in insufficient repression of the usually silent DUX4 gene only if there is a functional pLAM sequence nearby. In this case the degree of chromosomal shortening is correlated with the severity of the disease, and its earlier age of onset

• Type 2 [OMIM 158 901] is due to a mutation of a gene on chromosome 18p11.32 encoding for protein SMCHD1: this produces a hypomethylation of chromosomes 4 and 10, including both alleles of the D4Z4 zone and has the same consequence on repression of DUX4 gene