Facioscapulohumeral muscular dystrophy

Facioscapulohumeral muscular dystrophy
Timelapse of DUX4 being expressed in FSHD muscle cells
Synonyms	Landouzy–Dejerine muscular dystrophy, FSHMD, FSH
Pronounce
Specialty	N/A
Symptoms	Facial weakness, scapular winging, foot drop
Complications
Onset	Adolescence
Duration	Long term
Types	FSHD1, FSHD2
Causes	Genetic (inherited or new mutation)
Risks
Diagnosis	Genetic testing
Differential diagnosis	Limb-girdle muscular dystrophy (especially LGMD2A) Pompe disease, Mitochondrial myopathy, Polymyositis
Prevention
Treatment	N/A
Medication
Prognosis
Frequency	1 in 8333 to 1 in 15000
Deaths

DUX4 signaling in FSHD-affected skeletal muscle.

T1-weighted axial MRI at the level of thoracic vertebra T8, in which the right (left side of screen) lower trapezius is distinguishable, but the left lower trapezius is not.

Scapula-to-scapula scapulopexy

Facioscapulohumeral muscular dystrophy (FSHD) is a type of muscular dystrophy (MD) characterized by progressive weakness primarily affecting the skeletal muscles of the face (facio), scapula (scapulo), and upper arm (humerus). While initially, these muscles are predominantly affected, weakness may also develop in other areas of the body over time. The onset of symptoms typically occurs in early childhood, with manifestations becoming noticeable during the teenage years. Approximately 95% of affected individuals exhibit symptoms by the age of 20. In addition to muscular symptoms, FSHD may also present with non-muscular manifestations such as hearing loss and retinal blood vessel abnormalities.

FSHD is primarily inherited, although up to 30% of cases result from new mutations. The condition is attributed to incomplete suppression of the DUX4 gene, which is typically expressed during early human development. In 95% of cases, abnormal DUX4 expression arises from contraction of the D4Z4 repeat array in the subtelomeric region of chromosome 4 (locus 4q35), termed FSHD type 1 (FSHD1). The remaining 5% of cases, categorized as FSHD type 2 (FSHD2), result from various mutations. Diagnosis is typically confirmed through genetic testing.

Signs and Symptoms

Muscle weakness in FSHD predominantly affects the facial, scapular, and upper arm muscles, although other muscle groups may also be involved. The distribution and severity of weakness vary widely among individuals, even among identical twins. Weakness often begins unilaterally, affecting one side of the body before progressing to the other side. Symptoms usually appear in the teenage or early adult years, but onset may occur earlier or later, or some individuals may remain asymptomatic despite carrying the genetic mutation.

Facial weakness may lead to eyelid drooping, difficulty with facial expressions, and challenges with speech articulation. Weakness in the shoulder girdle muscles can result in sloping shoulders and winged scapulae, where the shoulder blade protrudes outward and upward. As the condition progresses, weakness may extend to the arms, causing difficulty with overhead activities and arm elevation. Pelvic girdle weakness may manifest as difficulty walking or maintaining an upright posture. Musculoskeletal pain, particularly in the neck, shoulders, and lower back, is common. Additionally, retinal blood vessel abnormalities and hearing loss may occur in some cases.

Genetics

FSHD is associated with abnormalities in the D4Z4 repeat array, leading to aberrant expression of the DUX4 gene. Hypomethylation of the surrounding genomic region allows transcription of DUX4 mRNA, resulting in muscle damage. FSHD is subclassified into FSHD1 and FSHD2 based on the underlying genetic mutations responsible for epigenetic dysregulation.

Management and Prognosis

Currently, there is no cure for FSHD, and treatment focuses on managing symptoms and improving quality of life. Physiotherapy, orthopedic interventions, and assistive devices such as braces may help address muscle weakness and functional limitations. Scapulothoracic fusion surgery may be considered to alleviate shoulder symptoms. Prognosis varies widely among individuals, with some experiencing minimal disability while others may become severely disabled and require mobility aids. Life expectancy is typically not affected, except in rare cases of respiratory insufficiency.

Research into potential therapies and interventions for FSHD continues, with ongoing efforts to elucidate the underlying disease mechanisms and identify therapeutic targets. Collaboration between clinicians, researchers, and patient advocacy groups is crucial in advancing our understanding and management of this complex genetic disorder.

Facioscapulohumeral muscular dystrophy Resources
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