Landouzy — Dejerine myodystrophy: clinical presentation, diagnosis, therapy. Clinical case



Landouzy — Dejerine muscular dystrophy (facioscapulohumeral muscular dystrophy) is a rare hereditary disease characterized by progressive weakness and atrophy of the muscles of the face, shoulders, and upper body. The article presents a clinical case of a young woman with this pathology, describes the features of her clinical picture, including the gradual development of symptoms, family history, and the results of an objective examination. Diagnostic methods, including electromyography and genetic tests that confirmed the presence of a mutation in the DUX4 gene, are considered in detail. Modern approaches to the treatment of Landouzy-Dejerine muscular dystrophy aimed at maintaining muscle function and improving the quality of life of patients are discussed.

Keywords: Landouzy Dejerine muscular dystrophy, facioscapulohumeral muscular dystrophy, clinical case, clinic, diagnostics, treatment

Introduction. Landouzy-Dejerine muscular dystrophy or facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder caused by ectopic expression of the transcription factor DUX4 in skeletal muscle. The prevalence of the disease in different populations ranges from 1:20,000 to 1:14,000, second only to Duchenne muscular dystrophy and myotonic dystrophy [1,2]. There is considerable variation in the presentation and progression of FSHD, and it can be diagnosed throughout life, from the very young to the very old. Although FSHD does not usually shorten life expectancy, it can lead to significant impairment of quality of life [3].

Objective. To review the literature, considering current information on the epidemiology, clinical picture, diagnosis and therapy of facioscapulohumeral muscular dystrophy; to present a clinical case.

Materials and methods. A review of the literature data was conducted, the PubMed database was used. A retrospective assessment of the medical history of a 25-year-old female patient was conducted, who was treated in the neurological department of a multidisciplinary hospital in Stavropol.

Clinical case. A 25-year-old woman was hospitalized in the neurology department of a multidisciplinary hospital with complaints of facial muscle weakness («cannot whistle, drink through a straw, etc».), mild hearing loss, and weakness of the back and arm muscles.

The disease began about three years ago in the form of weakness of the facial and arm muscles, with symptoms gradually progressing. The girl's father and paternal aunt noted weakness of the facial and limb muscles, difficulty getting up from a lying and sitting position, and also when walking. The patient's older brother (28 years old) is healthy.

His life history is not burdened, he denies the presence of chronic diseases, neuroinfections and head trauma, and denies bad habits.

Upon examination, the patient's condition is satisfactory. The skin and visible mucous membranes are clean. The lymph nodes are not enlarged. Vesicular breathing in the lungs, no wheezing. Heart sounds are clear and rhythmic. The abdomen is soft and painless on palpation. The liver and spleen are not enlarged.

Neurological status. Conscious, oriented, adequate. Emotionally labile. Full eye movements. Pupils D=S, photoreactions are preserved. The face is hypomimetic. When trying to close the eyes, there is an «eyelash symptom». «Tapir» lips. Swallowing, phonation and speech are not impaired. Muscle strength is symmetrically reduced in the proximal parts of the upper limbs. Weakness of the muscles of the back and anterior abdominal wall. Tendon reflexes are not evoked. There are no sensory disturbances. Romberg's test is stable. Gait is unchanged. «Winged» scapulae. Hypotrophy of the muscles of the shoulder girdle. Increased lumbar lordosis.

Complete blood count, complete urine analysis, general therapeutic blood biochemistry are within reference values. Blood for HIV, hepatitis B, C, syphilis is negative. Blood creatine phosphokinase is 950 U/l.

Needle electromyography was performed: a decrease in the duration of the motor unit potential by 40 %, the amplitude of the motor unit potential — up to 300–500 μV, 35 % polyphasic potentials of motor units.

Taking into account the clinical picture, age of onset, course of the disease, results of laboratory and instrumental studies, it was decided to conduct genetic testing: presence of a mutation in the DUX4 gene on 4q35.2.

Clinical diagnosis: facioscapulohumeral muscular dystrophy, type 1.

Discussion. There are currently two types of FSHD: FSHD1 and FSHD2. FSHD1 is inherited in an autosomal dominant manner, accounts for >95 % of all cases, and is characterized by a deletion of large repeat elements on the long arm of chromosome 4q (region D4Z4). Healthy individuals have more than 10 repeats, while patients with FSHD1 have 1 to 10 repeats [4]. FSHD2 is inherited in a digenic manner and occurs in less than 5 % of cases [3].

Since 1991, studies have shown that the prevalence of FSHD worldwide ranges from 2.03 to 6.8 per 100,000 people [5]. No clear racial or ethnic differences in FSHD are observed, but in one of the largest US registries, 95 % of participants were white, 4 % were Asian, and 0.9 % were Native American. Penetrance is thought to be lower in women than in men, and, on average, women are diagnosed at an older age and are often less severely affected [6].

FSHD has a characteristic pattern of muscle involvement and progression, but there is a high degree of variability both between patients from different families and within affected families from generation to generation. Both FSHD1 and FSHD2 have a similar clinical presentation. Typically, FSHD initially affects the muscles of the face, shoulder girdle, and upper arms (facial muscles, serratus anterior, rhomboid muscles, and biceps and triceps). Ptosis or difficulty swallowing are not usually present. The most common initial symptom is the inability to raise the arms above shoulder level. There may be a high degree of asymmetry in muscle involvement from side to side. The disease then progresses to involve the lower extremities, typically initially involving the distal musculature (tibialis anterior and gastrocnemius) in a facioscapulofibular pattern, then later involving the more proximal muscles (quadriceps and hamstrings) and the pelvic girdle. On neurological examination, numerous signs may be observed on the patient's face, including decreased superciliary fold, inability to close the eyes or hide the eyelashes when forced to close the eyes, a flattened transverse smile, and inability to tense the platysma muscle when the patient is asked to growl [7,8].

Supportive features for the diagnosis of FSHD include the following: new weakness involving the facial muscles or shoulder girdle musculature; positive family history; asymmetric muscle involvement; abdominal weakness; presence of retinal vasculopathy or hearing loss in early-onset FSHD. These features should be observed in the absence of the following: ptosis or extraocular muscle involvement, tongue involvement or swallowing difficulty, severe contractures, cardiomyopathy, electromyographic (EMG) or muscle biopsy findings suggesting an alternative diagnosis [9].

Current guidelines for the diagnosis of FSHD do not require EMG, serum creatine kinase, or muscle biopsy to make the diagnosis. Genetic testing is necessary for patients with characteristic clinical features [10].

The list of other neuromuscular conditions that present with a similar clinical picture is short and includes: some limb-girdle muscular dystrophies, scapuloperoneal syndromes, mitochondrial myopathy, inclusion body myositis, polymyositis, and acid maltase deficiency. Most of these can be readily distinguished from FSHD based on clinical presentation and subsequent testing [3].

There are no registered treatments approved for FSHD. Although many drugs have been tried in clinical trials (prednisone, diltiazem, albuterol and myostatin inhibitor), none have shown clear benefit, and treatment is mainly symptomatic [11,12].

The clinical case presented in this article describes a 25-year-old woman with progressive muscle weakness that began three years ago and affected the muscles of the face, back, and arms. Family history indicates similar symptoms in the patient's father and aunt, suggesting a hereditary nature of the disease. Objective examination data confirm the presence of muscle weakness, especially pronounced in the proximal parts of the upper limbs, back, and anterior abdominal wall. Electromyographic studies show changes characteristic of myopathy. Genetic testing revealed a mutation in the DUX4 gene, which confirms the diagnosis of facioscapulohumeral muscular dystrophy type 1.

Conclusion. Landouzy-Dejerine muscular dystrophy is a rare hereditary disease characterized by progressive weakness and atrophy of the muscles of the shoulder girdle and pelvic girdle. The clinical picture of the disease is varied and may include weakness of the muscles of the arms and legs, difficulty walking, difficulty lifting objects, and other symptoms. Diagnosis of Landouzy-Dejerine muscular dystrophy is based on the clinical picture, results of genetic testing, and data from an electrophysiological study. Treatment of this disease is aimed at maintaining muscle function, preventing contractures, and improving the quality of life of patients. It is important to note that Landouzy-Dejerine muscular dystrophy is an incurable disease, so the main focus is on symptomatic treatment and rehabilitation. Although a complete recovery is impossible, timely diagnosis and adequate therapy can significantly improve the quality of life of patients and slow down the progression of the disease.

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