Facioscapulohumeral Muscular Dystrophy (FSHD)

FSHD symptoms follow a characteristic asymmetric cranio-caudal pattern:

Facial Muscles (Early Signs):

• Orbicularis oculi weakness: difficulty closing the eyes completely.

• Orbicularis oris weakness: difficulty whistling or drinking through a straw.

• Facial asymmetry: often unilateral or more pronounced on one side.

• Ptosis (rare): its absence helps differentiate FSHD from myasthenia gravis.

Shoulder Girdle (Pathognomonic Sign):

• Scapular winging: a characteristic early sign.

• Atrophy of scapular fixators: involves the trapezius, rhomboids, and serratus anterior.

• Difficulty with arm elevation: challenges with combing hair or reaching for overhead objects.

• Asymmetric involvement: often clearly visible.

Humeral Muscles:

• Biceps brachii atrophy: the long head is typically spared.

• Forearm flexor weakness: leads to early functional impairment.

• Deltoid and triceps preservation: these muscles are often relatively spared.

Progression by Stages:

• Initial (Ages 20-30): asymptomatic facial weakness, intermittent scapular winging.

• Manifest (Ages 30-50): functional limitation of upper limbs, possible abdominal involvement.

• Advanced (Age >50): positive Beevor’s sign, lower limb weakness (tibialis anterior, peroneals, gluteal muscles).

Atypical Forms:

• Severe Infantile Forms: onset <10 years, hearing loss (75%), Coats’ retinopathy, and rare cases of epilepsy.

• Extramuscular involvement: strictly correlated with very small deletions (1-3 D4Z4 repeats).

• Clinical Evaluation:

  • Family history: assessment of autosomal dominant inheritance patterns.

  • Facial functional tests: evaluation of eye closure and whistling ability.

  • Assessment of scapular winging: clinical observation of the shoulder girdle.

  • Beevor’s test: evaluation of abdominal muscle involvement.

  • Asymmetric cranio-caudal pattern: identification of the characteristic progression.

  Laboratory Tests:

  • Creatine Kinase (CK): normal or slightly elevated levels (typically <5x the upper limit of normal); levels do not strictly correlate with disease severity.

  Genetic Diagnosis (Gold Standard):

  • D4Z4 methylation testing: used for initial screening.

  • Southern blot: confirmation of FSHD1 via repeat unit sizing.

  • SMCHD1 gene sequencing: performed to identify FSHD2.

  • 4qA/4qB haplotype analysis: to confirm the presence of a permissive haplotype.

  Emerging Technologies:

  • Optical Genome Mapping (OGM), long-read sequencing, and epigenomic analysis.

  Electromyography (EMG):

  • Myopathic pattern: characterized by short-duration, polyphasic potentials.

  • Spontaneous activity: detection of fibrillations.

  Muscle Imaging:

  • Muscle MRI: identification of the specific asymmetric FSHD pattern.

  • STIR sequences: detection of edema during active inflammatory phases.

  • T1-weighted sequences: assessment of fibro-fatty replacement.

  Specialist Evaluations:

  • Audiometry: recommended for infantile forms (hearing loss).

  • Fundus examination: to screen for retinopathy (Coats’ disease).

  • Spirometry: to monitor respiratory function in advanced stages.