Distal myopathy

Distal myopathy is a group of rare genetic disorders that cause muscle damage and weakness, predominantly in the hands and/or feet. Mutation of many different genes can be causative. Many types involve dysferlin.^[1]

Distal myopathy
Other names	Distal muscular dystrophy
Red depicts the preferentially affected areas in distal myopathy.
Specialty	Neurology, neuromuscular medicine
Symptoms	Weakness of hands and/or feet
Complications	Cardiomyopathy
Usual onset	Variable
Duration	Lifetime
Types	Classic, myofibrillar myopathy, other
Causes	Genetic mutation of various genes
Diagnostic method	Genetic testing, muscle biopsy
Frequency	Rare

Signs and symptoms

All of the different types affect different regions of the extremities and can show up as early as 5 years of age to as late as 50 years old. Distal myopathy has slow progress therefore the patient may not know that they have it until they are in their late 40s or 50s.^{[citation needed]}

Miyoshi myopathy affects the posterior muscles of the lower leg, more so than the anterior muscles of the lower leg.^[2][3]

Cause

DYSF

The cause of this myopathy is very hard to determine because it can be a mutation in any of at least eight genes and not all are known yet. These mutations can be inherited from one parent, autosomal dominant, or from both parents, autosomal recessive. There are eight known types of distal myopathy.^{[citation needed]}

Types

Classic distal muscular dystrophies

Type	Eponym	Inheritance	OMIM	Gene	Locus	Gene also implicated in:
Late adult-onset type 1[4]	Welander	AD[5]	604454	TIA1[6]	2p13[7]
Late adult-onset type 2a[5] - Finnish (tibial)	Udd	AD[5]	600334	TTN[5]	2q31.2
Late adult-onset type 2b[5]	Markesbery–Griggs	AD[8]		ZASP[5]	10q23.2
Early adult-onset type 1[4]	Nonaka	AR[5]	605820	GNE[5]	9p13.3
Early adult-onset type 2[4]	Miyoshi	AR[5]	254130	DYSF[5]	2p13.3-p13.1	limb-girdle muscular dystrophy type 2B.[9]
Distal myopathy with anterior tibial onset (DMAT)[10][11]			606768			DMAT can be considered a variant of Miyoshi.
Early adult-onset type 3[4]	Laing (Gower)	AD[5]	160500	MYH7[5]	14q11.2
AD = autosomal dominant; AR = autosomal recessive

Myofibrillar myopathies classifiable as distal myopathy

Type	Eponym	Inheritance	OMIM	Gene	Locus	Gene also implicated in:
Desmin — adult onset (MFM1)[5] Hereditary inclusion-body myositis type 1[5]		AD
αB-crystallin — early - mid adult (MFM2)[5]		AD
ZASP— late adult (MFM4)[5]		AD
Scapuloperoneal[5]		AD
MFM = myofibrillary myopathy; AD = autosomal dominant; AR = autosomal recessive

Other distal muscular dystrophies

Type	Eponym	Inheritance	OMIM	Gene	Locus	Gene also implicated in:
Distal myopathy with vocal cord and pharyngeal weakness[4]		AD[5]	606070	MATR3[5]	5q31[5]	Amyotrophic lateral sclerosis 21 (ALS21). One study suggests that all cases are ALS, justifying reclassification.[12]

Diagnosis

In terms of diagnosis, Vocal cord and pharyngeal distal myopathy should be assessed via serum CK levels, as well as muscle biopsy of the individual suspected of being afflicted with this condition^[13]

Management

As of 2011, no disease modifying treatments are known.^[8] Foot drop can be managed with ankle-foot orthoses or surgical tendon transfer,^[8] in which the tibialis posterior muscle is repurposed to function as a tibialis anterior muscle. In select types of distal myopathy, evaluation of the heart may be indicated.^[8] Scoliosis and contractures can be surgically managed.^[8] In 2024 a drug to treat distal myopathy was approved in Japan.^[14]