Facioscapulohumeral dystrophy (Landouzy-Déjerine dystrophy)

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Background     Histopathology & Immunohistochemistry    Differential Diagnosis    

BACKGROUND AND CLINICAL INFORMATION: Head  

Summary    Molecular Pathology    Clinical Features

Summary: Fascioscapulohumeral dystrophy (FSHD) affects predominantly the shoulder girdle and the facial muscles and is transmitted in an autosomal dominant pattern. It may occur as a clinical triad of fascioscapulohumeral muscle weakness, hearing loss, and retinal vasculopathy. Subclinical cases may be identified after careful examination.  Wheelchair bound severe cases, however, may occur. This condition is relatively mild and progression is slow. The facial weakness may precede the scapulohumeral muscles and the severity within a pedigree is variable. In contrast to its name, muscle of the lower extremity and the pelvic girdle can also be involved. Other features include high tone hearing loss and retinal vascular changes. Cardiac involvement is usually not part of the disease.

Biopsy site: Deltoid and other muscles that have weakness. The pathologic changes correlates with weakness and duration of disease can vary from minimal non-specific changes to end-stage muscle. This is particularly true in children.

Age of onset: It is difficult to sharply define the age of onset. If the self-awarelss of facial muscle weakness is defined as the time of onet, most cases has onset in teenage. Congenital onset characterized by facial asymmetry can also occur.

Genetics: Autosomal dominant with variation of severity within the same pedigree. Autosomal recessive and sporadic cases are also found. Sporadic cases tend to be more severe.

Molecular pathology: Linked to deletion of an integral number of 3.3 kb tandem repeats at the subtelomere of chromosome 4 (4q35). FSHD1A are cases that are linked to chromosome 4q35, FSHD1B are cases that are not linked to chromosome 4q35.

·        The D4Z4 locus (EcoRI restriction fragments, site bounded by p13E-11 probe in normal individuals contains 12 to 85 nearly identical tandem repeats of approximately 3.3 kb each. The EcoR1 fragments in normal individuals is 35-300 kb, those in FSHD1A is under 35 kb and contain only up to 9 repeats.

Clinical:

·        Genenral: This is a relatively mild dystrophy with slow progression. It may occur as a clinical triad of fascioscapulohumeral muscle weakness, hearing loss, and retinal vasculopathy. The muscle weakness is not specific and overlaps with other neuromuscular diseases including myasthenia gravis, other muscular dystrophy, myotubular myopathy, and other myopathies. The cardiac muscle is usually not involved. CK level: Elevated CK level rarely exceeds 5 times of normal. It decline significantly with age and duration of the disease.

·        Asymmetry: Involvement of muscle is largely asymmetrical.

·        Variation: The weakness may be very focal and slight. The diagnosis can usually be made by clinical examination. Subclinical cases may be identified after careful examination. Facial weakness may precede shoulder weakness. They can also occur without facial weakness. Severe wheelchair bound cases can occur.

·        Facial weakness: Inability to screw the eyes closed and bury the eyelashes, to purse the lips, or blow the whistles.

·        Shoulder weakness: Muscles of the upper arm and sternocleidomastoid muscles are most affected. Posterior neck muscles such as the trapezii are spared. Difficulty in rising the arms when the shoulders are abducted. Striking upward riding of the scapulae giving a characteristic stepwise or terraced appearance to the shoulders.

·        Other muscles may be involved, particularly in cases of longer duration and in more severe cases.

·        Sensorineural hearing loss: This is not an uncommon sign of early onset FSHD. The high tone range is typically affected. There is a tendency towards increasing hearing impairment with age.

·        Ocular changes: Retinovasculopathic changes can be seen in a good proportion of patient and can be well demonstrated by fluorescein angiography. Ocular muscles are not involved.

HISTOPATHOLOGY AND IMMUNOHISTOCHEMISTRY: Head  

General: Similar to other muscular dystrophies, the histologic picture is non-diagnostic. Both fiber types may be affected. There is variation of fiber size and the smaller fibers are often type 1 fibers. Endomysial fibrosis between fibers may be found but they are never as prominent and abundant as in Duchenne muscular dystrophy.

NADH-TR: Abnormal reaction pattern that gives a “lacey” appearance may be seen.

Inflammatory infiltration: A subtle increase in interstitial inflammatory cells can be demonstrated by Immunostaining for lymphocytes. In a minor proportion of cases, there is extensive inflammatory cell infiltration. Invasion of necrotic fibers by mononuclear cells (a phenomenon in polymyositis and inclusion body myositis) is not present but “degenerating” and “partially degenerating” fibers are invaded by histiocytes.

DIFFERENTIAL DIAGNOSIS: Head

Inflammatory myopathies.