Congenital Muscular Dystrophy (CMD)

Types Of CMD List

The list includes 33 types of congenital muscular dystrophy, listed in alphabetical order.

Types of Congenital Muscular Dystrophies

CMD with adducted (drawn inward) thumbs, ophthalmoplegia (paralyzed eye muscles) and intellectual disability

Description: rare form of CMD with inward-drawn thumbs, contractures (permanent shortening) of the toe joints, weakness, lack of muscle tone, delayed walking, paralysis of eye muscles and intellectual disability

Molecular basis: unknown

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with cardiomyopathy

Description: weakness beginning within first year; delayed motor milestones; slowly progressive; walking achieved in adolescence; contractures of the joints, neck and spine; progressive cardiomyopathy (cardiac muscle deterioration) beginning ages 5-12; cardiac rhythm abnormalities

Molecular basis: mutations in titin gene, causing deficiency of titin protein; protein normally plays a role in muscle assembly and force transmission in skeletal and cardiac muscles

Recent sequencing approaches are able to link titin mutations to dilated cardiomyopathy. Some of these mutations can also be linked to irregular heart rhythms like atrial fibrillation and ventricular tachycardia, which are serious conditions but can be managed by treatment.

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with central nervous system atrophy and absence of large myelinated fibers in peripheral nervous system

Description: onset in newborn period; weakness, lack of muscle tone, poor motor function; respiratory failure in some; diminished size of major parts of the brain; joint contractures

Molecular basis: unknown

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with cerebellar atrophy (diminished size of the cerebellum, a part of the brain involved in motor control)

Description: nonprogresssive form of CMD with onset by 7 months, weakness, lack of muscle tone, delayed motor milestones, lack of coordination of movements, difficulty speaking, involuntary eye movements and intellectual disability

Molecular basis: unknown

Inheritance pattern: possibly recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with desmin inclusions (abnormal accumulations of the muscle protein desmin in some muscle fibers)

Description: onset of progressive weakness and low muscle tone at birth or during early infancy; small muscles; cardiac abnormalities in some; spinal curvatures at 8-14 years; joint contractures; respiratory impairment

Molecular basis: mutations in SEPN1 gene, causing deficiency of SEPN1 protein; protein is thought to play a role in early development or regeneration of muscle tissue

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with integrin alpha 7 mutations

Description: early-onset low muscle tone, weakness; may walk at age 2-3; respiratory involvement with disease progression

Molecular basis: mutations in the integrin-alpha 7 gene, causing a deficiency of the integrin alpha 7 beta 1 protein; protein normally provides a link between muscle fibers and the surrounding matrix

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with joint hyperlaxity (abnormally flexible joints)

Description: weakness, poor muscle tone and contractures from birth; slowly progressive; walking at 1-3 years; wheelchair later, between teens and 30s; reduced respiratory capacity that does not progress; contractures in some joints and abnormal flexibility in others; spinal curvature possible; normal intelligence

Molecular basis: thought to be due to mutations in the integrin alpha 9 gene, causing a deficiency of the integrin alpha 9 protein; protein normally plays a role in how cells stick to each other and to their surroundings

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with familial junctional epidermolysis bullosa

Description: onset of weakness or poor muscle tone, with skin blistering, at birth; skin blisters with injury and heat; slowly progressive; many need wheelchair by age 10; elbow contractures; respiratory impairment; cardiomyopathy; diminished brain size; treatment with 3,4-diaminopyridine, which increases signal transmission from nerve to muscle, may be helpful

Molecular basis: mutations in the gene for the plectin protein, causing a deficiency of this protein; protein is thought to provide mechanical strength to cells and tissues

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with muscle hypertrophy (enlargement of muscles); also called MDC1C

Description: low muscle tone and weakness starting in first weeks of life; may sit unassisted but walking not achieved; some muscles enlarged, especially calf muscles; other muscles small, especially in shoulder area; joint contractures in some; cognitive function usually normal; mild intellectual disability or speech problems can occur

Molecular basis: mutations in gene for fukutin-related protein (FKRP), leading to FKRP deficiency; protein normally helps glycosylate (sugar-coat) a protein called alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with muscle hypertrophy and respiratory failure; also called MDC1B

Description: early-onset weakness with involvement of the diaphragm and respiratory failure; walking at 1.5 to 2.5 years; weakness does not appear to progress; generalized muscle enlargement; contractures in ankles; spinal rigidity in about 50 percent; normal intelligence

Molecular basis: mutations in unknown gene on chromosome 1

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with muscle hypertrophy and severe intellectual disability; also called MDC1D

Description: onset around 5 months, with low muscle tone and weakness; some muscles enlarged; global developmental delay; profound intellectual disability; contractures of ankles and elbows

Molecular basis: mutations in LARGE gene, leading to deficiency of LARGE protein; protein thought to play a role in sugar-coating (glycosylation) of alpha-dystroglycan protein

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with myasthenic syndrome

Description: rare form of CMD with onset by time of birth; weakness, lack of muscle tone, small muscles; slowly progressive; respiratory involvement possible; most survivors able to walk as children and adults; normal intelligence

Molecular basis: DOK7 gene mutation leading to deficiency of DOK7 protein; protein normally plays a role in forming the connections between nerves and muscles

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with (early) spinal rigidity

Description: onset birth to 1 year or during first decade of life; early-onset poor muscle tone, weakness; respiratory capacity often reduced; small muscles; early improvement, followed by stabilization or slow decline; spinal rigidity beginning ages 3-7, with limited ability to flex the neck and spine; spinal curvature beginning ages 4-12 and progressing; joint contractures; minor cardiac abnormalities, if any; normal intelligence

Molecular basis: mutations in SEPN1 gene, causing deficiency of SEPN1 protein; protein is thought to play a role in early development or regeneration of muscle tissue

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with spinal rigidity and lamin A/C abnormality

Description: weakness within first year; respiratory involvement; rigid spine, curved spine, curved feet; cardiac rhythm abnormalities in some; premature aging in some; abnormalities of fatty tissue in some

Molecular basis: mutation in lamin A/C gene, causing an abnormality in the lamin A or C proteins; these normally form part of a membrane that surrounds the cell nucleus

Inheritance pattern: dominant (requiring a mutation in only one copy of a gene to produce symptoms)

CMD with spinal rigidity and selenoprotein deficiency

Description: early-onset weakness; developmental delay; reduced respiratory capacity; fatigue; skin abnormalities; hearing loss; straight, rigid spine

Molecular basis: mutations in SBP2 gene, causing deficiency of SBP2 protein; protein normally involved in the production of selenoproteins

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

CMD with structural abnormalities of mitochondria (energy-producing subunits of cells)

Description: poor muscle tone, weakness from birth, with late walking; loss of muscle tissue; cardiomyopathy; intellectual disability; mitochondria (seen in muscle biopsy samples) are enlarged and have an abnormal structure

Molecular basis: mutations in choline kinase beta gene, which leads to deficiency of choline kinase beta protein; protein normally helps make a key substance in muscle and brain

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Fukuyama CMD; also called MDDGA4

Description: common in Japan; rare in Western countries; spectrum of severity; weakness and low muscle tone within first year; some achieve walking; joint contractures; spinal curvatures; seizures in 50 percent; intellectual disability; eye involvement

Molecular basis: mutations in fukutin gene, causing a deficiency of fukutin protein; protein normally helps sugar-coat (glycosylate) the alpha-dystroglycan protein in muscle and brain tissue

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Merosin-deficient CMD; also called MDC1A

Description: early-onset weakness and low muscle tone; spectrum of severity; some learn to walk at age 2-3 years; spinal curvature; contractures; respiratory impairment; intelligence often normal; seizures in about 20 percent

Molecular basis: mutations in laminin alpha 2 gene, leading to deficiency of laminin alpha 2 protein; leads to deficiency of laminin 211 protein, also known as merosin; protein normally helps connect muscle fiber with surrounding matrix

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Merosin-positive CMD; this is an old term referring to a variety of CMD types in which merosin is normal

Description: examples are CMD with early spinal rigidity; CMD with muscle hypertrophy; CMD with muscle hypertrophy and respiratory failure; CMD with myasthenic syndrome; and Ullrich CMD; see individual listings for different types

Molecular basis: variety of gene mutations, causing variety of protein defects that do not affect merosin protein

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Santavuori muscle-eye-brain disease

Description: low muscle tone at birth; slow development; intellectual disability; eye abnormalities

Molecular basis: Mutations in POMGnT1 gene, causing deficiency of POMGnT1 protein; protein normally helps sugar-coat (glycosylate) the alpha-dystroglycan protein

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Ullrich CMD

Description: early-onset weakness, poor muscle tone; severity varies; some joints have contractures; some joints have hyperlaxity (excessive flexibility); spinal rigidity, curvature; respiratory impairment; soft skin; normal cardiac function; normal intelligence

Molecular basis: mutations in COLGA1, COL6A2 or COL6A3 genes, causing deficiency of or abnormalities in collagen 6 protein; protein normally has an anchoring function in many tissues, including the matrix surrounding muscle fibers

Inheritance pattern: dominant (requiring a mutation in only one copy of a gene to produce symptoms) or recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in B3GNT1 gene, causing deficiency of the B3GNT1 protein; protein normally helps sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA1 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in POMT1 gene, causing deficiency of POMT1 protein; protein normally helps sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA2 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in POMT2 gene, causing deficiency of POMT2 protein; protein normally helps sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA3 type; same as Santavuori muscle-eye-brain disease

Walker-Warburg syndrome: MDDGA4 type; same as Fukuyama CMD

Walker-Warburg syndrome: MDDGB5 type; same as CMD with muscle hypertrophy (MDC1C)

Walker-Warburg syndrome: MDDGA6 type; same as CMD with muscle hypertrophy and severe intellectual disability (MDC1D)

Walker-Warburg syndrome: MDDGA7 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in ISPD gene, causing deficiency of the ISPD protein; protein normally helps sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA8 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in GTDC2 gene, causing deficiency of the GTDC2 protein; protein may help sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA10 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in TMEM5 gene, causing deficiency of the TMEM5 protein; protein may help sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA11 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: mutations in B3GALNT2 gene, causing deficiency of the B3GALNT2 protein; protein normally helps sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)

Walker-Warburg syndrome: MDDGA12 type

Description: early-onset weakness with brain and eye abnormalities; intellectual disability

Molecular basis: Mutations in SGK196 gene, causing deficiency of SGK196 protein; protein normally may help sugar-coat (glycosylate) alpha-dystroglycan

Inheritance pattern: recessive (requires mutations in both copies of a gene to produce symptoms)