Disease Variants

LGMD Subtypes

OVERVIEW

Limb-girdle muscular dystrophy (LGMD) is an umbrella term for a group of genetic diseases with significant variation in their symptoms and severity

 

 

34
LGMD subtypes currently identified
Each is caused by a particular gene mutation
~8
LGMDs are subtype 1
These are inherited in an autosomal dominant pattern
~26
LGMDs are subtype 2
These are inherited in an autosomal recessive pattern

About 10% of people with LGMD have subtype 1,which has an autosomal dominant inheritance pattern—meaning they inherited the gene mutation from only one parent. Generally, most LGMD1 subtypes first show symptoms later in life (adolescence to late adulthood) and are associated with milder muscle weakness.

The other ~90% of people with LGMD have subtype 2,which has an autosomal recessive pattern—meaning they inherited the gene mutation from both parents. These subtypes generally show symptoms earlier in life (childhood to young adulthood) and are associated with moderate to severe muscle weakness.

New therapies are in development

New therapies are in development. Knowing your specific subtype provides valuable information to help you discuss with your doctor which disease management strategies may be appropriate.

To learn more about clinical trials visit clinicaltrials.gov to search for “LGMD” (under “Condition”), or speak with your healthcare provider.
 

Sarepta’s LGMD Research Focus: 6 Subtypes

Sarepta Therapeutics is currently researching potential new gene therapies for six LGMD subtypes. They are all subtype 2, inherited in an autosomal recessive pattern.

Three of these (LGMD2C, LGMD2D, LGMD2E) are caused by a deficiency of one of the sarcoglycans, a group of proteins responsible for preventing muscle damage during contraction. The “sarcoglycanopathy” subtypes (which also include a fourth, LGMD2F) are estimated to account for 15-20% of all LGMD cases.

LGMD2A is caused by an enzyme deficiency that leads to waste build-up in muscle cells. The other two subtypes (LGMD2B, LGMD2L) result from protein deficiencies that prevent proper muscle membrane repair.

To learn more about clinical trials, visit www.clinicaltrials.gov and search for “LGMD,” or speak with your healthcare provider.
 

A Note About Naming

You may see variants of LGMD subtype names, as there are several systems in use. Historically, the numerals “1” and “2” have been used to designate the inheritance pattern, followed by a letter indicating the subtypes’ order of discovery. More recently, an alternate system uses the letter “D” for some type-1 dominant inheritance variants, and the letter “R” for some type-2 recessive inheritance variants, plus a number for the order of discovery.

The subtypes are also sometimes referred to by the gene or protein abnormality involved; for example, LGMD2E is also called beta-sarcoglycanopathy because it results from a mutation of the beta-sarcoglycan gene (“-opathy” means a disease or disorder).

 

 

LEARN ABOUT THE LGMD SUBTYPES

LGMD1A (z-disk proteinopathy or myofibrillar myopathy)

An autosomal dominant subtype, LGMD1A is characterized by weakness of the shoulder, upper arm, and hip muscles.

  • Gene mutation: MYOT
  • Protein involved: myotilin
  • Age of first symptoms: 18-35 years

 Signs, symptoms, & disease progression

  • Muscle weakness occurs more often in the legs, but also occasionally in the arms
  • May involve damage to and weakening of the heart
  • A distinctive feature of this subtype is weakening of speaking muscles, resulting in a nasal and/or soft speaking voice
  • May have normal to high levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged), up to 9 times normal
LGMD1B (nuclear envelopathy or Emery-Dreifuss muscular dystrophy)

An autosomal dominant subtype, LGMD1B can vary considerably in its signs and symptoms across different people.

  • Gene mutation: LMNA
  • Protein involved: lamin A/C
  • Age of first symptoms: 5-25 years

Signs, symptoms, & disease progression

  • Weakness of the shoulder and hip muscles usually develops in the early teens
  • Contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement) that affect posture and gait, and may occur before muscle weakness develops
  • Serious damage to and weakening of the heart, which may occur before other muscle weakness develops
  • May have normal to slightly higher levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged), up to 5 times normal
LGMD1C (rippling muscle disease or caveolae-associated muscular dystrophy)

An autosomal dominant subtype, LGMD1C can vary considerably in its signs, symptoms, and rate of progression across different people, even within the same family.

  • Gene mutation: CAV3
  • Protein involved: caveolin 3
  • Age of first symptoms: 1st decade – late adulthood

Signs, symptoms, & disease progression

  • Weakening and damage of the heart is common
  • Very high levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
  • This subtype encompasses six distinct types of effects:
    • Enlargement of calf muscles, associated with weakness or pain caused by exercise
    • Rippling muscle disease, where muscles tense, “bunch up,” or visibly ripple from touch or movement
    • Weakness of the limbs
    • Elevated levels of CK but without outward muscle symptoms
    • Thickening of the heart muscle that causes less effective pumping of blood through the body
    • Muscle pain, exercise intolerance, and muscle damage that can lead to serious kidney disease
LGMD1D (LGMDD1 or z-disk proteinopathy)

An autosomal dominant subtype, LGMD1D occurs in slightly different forms depending on age of disease onset.

  • Gene mutation: DNAJB6
  • Protein involved: DNAJ/HSP40 homolog, subfamily B, member 6
  • Age of first symptoms: 2nd decade – upper middle age

 Signs, symptoms, & disease progression

  • The adult-onset form is characterized by more slowly progressing weakness in limb muscles closer to the body, and patients generally remain mobile into their 60s
  • The childhood-onset form may affect muscles of the arms and legs and can lead to loss of mobility by early adulthood
  • The childhood-onset form may also involve breathing difficulties
  • In all forms, creatine kinase (CK, an enzyme released into the blood when muscles are damaged) may be normal or elevated
LGMD1E (z-disk proteinopathy or myofibrillar myopathy)

An autosomal dominant subtype, LGMD1E is characterized by severe muscle weakness, not just around the limb-girdle but also typically extending out to the arms and legs.

  • Gene mutation: DES
  • Protein involved: desmin
  • Age of first symptoms: generally puberty – 50 years, but some earlier cases have been reported

 Signs, symptoms, & disease progression

  • Muscle weakness may be concentrated specifically around the shoulder blades and in the smaller leg muscles below the knee (scapuloperoneal syndrome)
  • May involve heart weakening and damage
  • Breathing difficulties occur in 25% of patients
  • Weakening of the swallowing muscles is common
  • Creatine kinase (CK, an enzyme released into the blood when muscles are damaged) may be normal or slightly elevated
LGMD1F (LGMDD2 or nuclear envelopathy)

An autosomal dominant subtype, LGMD1F occurs in different variants depending on age of disease onset.

  • Gene mutation: TNP03
  • Protein involved: transportin
  • Age of first symptoms: infancy – late adulthood

Signs, symptoms, & disease progression

  • The adult-onset form is characterized by weakness in the hip and shoulder muscles, with varying rates of disease progression and severity but generally milder symptoms
  • The childhood-onset form is characterized by more severe muscle weakness and symptoms
  • The childhood-onset form typically leads to wheel-chair dependence and also involves breathing difficulties
LGMD1G (LGMDD3)

An autosomal dominant subtype, LGMD1G is an adult-onset form with generally slower disease progression.

  • Gene mutation: HNRNPDL
  • Protein involved: heterogeneous nuclear ribonucleo-protein D-like
  • Age of first symptoms: adulthood

Signs, symptoms, & disease progression

  • Typically affects limb muscles closer to the body, with the hips more often affected than the shoulders
  • Generally slower rate of progression
  • A distinctive feature of this subtype is difficulty bending the fingers and/or toes
LGMD1H

An autosomal dominant subtype, LGMD1H is characterized by slowly progressive muscle weakness.

  • Gene mutation: mapped to chr3p23-p25.1
  • Protein involved: unconfirmed
  • Age of first symptoms: 2nd – 5th decade

Signs, symptoms, & disease progression

  • Decreased reflexes
  • Wasting of limb muscles closer to the body
  • Enlargement of calf muscles, with or without weakness
  • Occasionally, elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
  • Slow progressive weakness
LGMD2A (LGMDR1 or calpainopathy)

An autosomal recessive subtype, LGMD2A has high prevalence among the subtypes, occurring in an estimated 15-40% of LGMD patients.

  • Gene mutation: CAPN3
  • Protein involved: calpain-3
  • Age of first symptoms: highly variable, from 2 to 50 years of age

Signs, symptoms, & disease progression

  • Weakness of the hip and thigh muscles (similar to Becker and Duchenne muscular dystrophies)
  • Some patients also experience weakness in the shoulder area muscles
  • High levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
  • May involve scoliosis (curving of the spine) and contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement) of the elbows and calves
LGMD2B (LGMDR2 or dysferlinopathy)

An autosomal recessive subtype, LGMD2B is related to another disease called Myoshi myopathy, which has the same underlying genetic cause but slightly different symptoms.

  • Gene mutation: DYSF
  • Protein involved: dysferlin
  • Age of first symptoms: typically 15-30 years

 Signs, symptoms, & disease progression

  • Typical onset in adolescence with weakness of the hip and shoulder muscles
  • Slow disease progression
  • Very high levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2C (LGMDR5 or gamma-sarcoglycanopathy)

An autosomal recessive subtype, LGMD2C is generally very debilitating but can sometimes occur in a milder, later-onset form if there is only a partial deficiency of the associated protein.

  • Gene mutation: SGCG
  • Protein involved: gamma-sarcoglycan
  • Age of first symptoms: typically 1-15 years, sometimes later with partial protein deficiency

Signs, symptoms, & disease progression

  • Weakness of hip muscles of arms and legs, leading to difficulties with running and walking
  • Enlargement of calf muscle, tongue, and heart
  • Protrusion of the shoulder blades and extreme curvature of the lower back
  • Late progression may involve scoliosis (curving of the spine) and joint contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement)
  • Patients can progress to wheelchair dependence by ~15 years
  • May involve breathing difficulties and heart problems
  • Elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2D (LGMDR3 or alpha-sarcoglycanopathy)

An autosomal recessive subtype, LGMD2D is believed to be the most common of the sarcoglycanopathies.

  • Gene mutation: SGCA
  • Protein involved: alpha-sarcoglycan
  • Age of first symptoms: typically 1-15 years, sometimes later with partial protein deficiency

Signs, symptoms, & disease progression

  • Weakness of hip muscles of arms and legs, leading to difficulties with running and walking
  • Enlargement of calf muscle and tongue, and rarely of the heart
  • Protrusion of the shoulder blades and extreme curvature of the lower back
  • Late progression may involve scoliosis (curving of the spine) and joint contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement)
  • Patients can progress to wheelchair dependence by ~15 years
  • May involve breathing difficulties
  • Elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2E (LGMDR4 or beta-sarcoglycanopathy)

An autosomal recessive subtype, LGMD2E is a debilitating subtype similar in symptoms and effects to LGMD2C.

  • Gene mutation: SGCB
  • Protein involved: beta-sarcoglycan
  • Age of first symptoms: typically 1-15 years, sometimes later with partial protein deficiency

Signs, symptoms, & disease progression

  • Weakness of hip muscles of arms and legs, leading to difficulties with running and walking
  • Enlargement of calf muscle, tongue, and heart
  • Protrusion of the shoulder blades and extreme curvature of the lower back
  • Late progression may involve scoliosis (curving of the spine) and joint contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement)
  • Patients can progress to wheelchair dependence by ~15 years
  • May involve breathing difficulties and heart problems
  • Elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2F (LGMDR6 or delta-sarcoglycanopathy)

An autosomal recessive subtype, LGMD2E is a debilitating subtype similar in symptoms and affects to LGMD2C.

  • Gene mutation: SGCD
  • Protein involved: delta-sarcoglycan
  • Age of first symptoms: typically 1-15 years, sometimes later with partial protein deficiency

Signs, symptoms, & disease progression

  • Weakness of hip muscles of arms and legs, leading to difficulties with running and walking
  • Enlargement of calf muscle, tongue, and heart
  • Protrusion of the shoulder blades and extreme curvature of the lower back
  • Late progression may involve scoliosis (curving of the spine) and joint contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement)
  • Patients can progress to wheelchair dependence by ~15 years
  • May involve breathing difficulties and heart problems
  • Elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2G (LGMDR7 or z-disk proteinopathy)

An autosomal recessive subtype, LGMD2G can vary considerably in its signs and symptoms across different people. Females may be less severely affected than males.

  • Gene mutation: TCAP
  • Protein involved: titin-cap / telethonin
  • Age of first symptoms: 9-15 years 

Signs, symptoms, & disease progression

  • Characterized by significant weakness of the shoulder and/or hip muscles
  • Muscle weakness may extend into the upper and/or lower limbs
  • May involve weakened thigh muscles, causing difficulty running, and difficult lifting the feet due to weakened lower leg muscles
  • Calf muscles may become enlarged
  • Heart weakening and problems occur in approximately 50% of patients
  • Females appear to be less severely affected than males
LGMD2H (LGMDR8)

An autosomal recessive subtype, LGMD2H is characterized by relatively slowly progressive muscle weakness and can vary considerably in its severity across different people.

  • Gene mutation: TRIM32
  • Protein involved: tripartite motif-containing protein 32
  • Age of first symptoms: 8-27 years 

Signs, symptoms, & disease progression

  • Early signs typically include weakness of the hip and thigh muscles, leading to a “waddling” gait and difficulty climbing stairs
  • Muscle weakness may also extend to the upper back and shoulders, facial muscles, and calves
  • Patients can progress to wheelchair dependence late in life
  • Variable in severity
LGMD2I (LGMDR9 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2I can vary considerably in its age of onset and severity across different people.

  • Gene mutation: FKRP
  • Protein involved: fukutin-related protein
  • Age of first symptoms: infancy – 4th decade

Signs, symptoms, & disease progression

  • Weakness of the hip muscles, sometimes extending into the leg muscles, causing difficulty running and walking
  • Weakness of the shoulder and/or upper arm muscles
  • May involve enlargement of the calf muscles and/or tongue
  • May involve severe curvature of the lower back
  • Heart and breathing difficulties are common, with weakening of the heart muscle occurring in approximately 50% of patients
  • Variable in severity
LGMD2J (LGMDR10 or z-disk proteinopathy)

An autosomal recessive subtype, LGMD2J occurs in different variants depending on age of disease onset.

  • Gene mutation: TTN
  • Protein involved: titin
  • Age of first symptoms: childhood – late adulthood

Signs, symptoms, & disease progression

  • The childhood-onset form is characterized by weakness of the hip and shoulder muscles
  • The adult-onset form may involve arm muscle weakness, weakness of the muscles around the shins, and weakening/wasting of the calf muscles
LGMD2K (LGMDR11 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2K typically first presents in early childhood.

  • Gene mutation: POMT1
  • Protein involved: protein O-mannosyl-transferase 1
  • Age of first symptoms: 1-3 years

Signs, symptoms, & disease progression

  • Mild weakness of the limb muscles, primarily closer to the body, with difficulty running and climbing stairs, and increased fatigue from exertion
  • Weakness may extend to the calf and thigh muscles
  • Contractures of the ankles (hardening and deformity of connective tissues that cause stiffness and restrict movement) may occur
  • May involve language difficulties and cognitive limitations
  • High levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged), up to 20-40 times normal
LGMD2L (LGMDR12 or anoctaminopathy)

An autosomal recessive subtype, LGMD2L most affects the lower limbs.

  • Gene mutation: ANO5
  • Protein involved: anoctamin-5
  • Age of first symptoms: typically averages 10-20 years of age

 Signs, symptoms, & disease progression

  • Weakness of the leg muscles, especially the thighs
  • Effects may be asymmetric, with one leg more affected than the other
  • High levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2M (LGMDR13 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2M involves skeletal muscle weakness that appears in early childhood. It has the same underlying genetic cause as another disorder called Fukuyama muscular dystrophy, but different symptoms.

  • Gene mutation: FKTN
  • Protein involved: fukutin
  • Age of first symptoms: 4 months – 4 years

Signs, symptoms, & disease progression

  • Skeletal muscle weakness that begins in early childhood
  • Weakness is more pronounced in the lower rather than upper limbs, leading to difficulties climbing stairs
  • Weakening usually begins in muscles closer to the body but may extend to the calves, thighs, and upper arms
  • Common cause of Fukuyama muscular dystrophy
LGMD2N (LGMDR14 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2N is a rare, early-onset subtype that has been studied in two diagnosed patients.

  • Gene mutation: POMT2
  • Protein involved: protein O-mannosyl-transferase 2
  • Age of first symptoms: early childhood 

Signs, symptoms, & disease progression

Note that these signs are based on two diagnosed patients, with widely varying disease presentations:

  • A 5-year-old female patient displayed minimal outward symptoms, but additional exams showed abnormally protruding shoulder blades, weakened calf muscles, and slowness in running and getting up
  • An 18-month-old patient exhibited developmental delays and intellectual disabilities, as well as muscle weakness and abnormalities in electrical impulses running through heart muscle
LGMD2O (LGMDR15 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2N is a rare subtype that has been studied in one diagnosed patient.

  • Gene mutation: POMGNT1
  • Protein involved: protein O-mannose beta-1, 2-N-acetyl-glucosaminyl-transferase 1
  • Age of first symptoms: undefined

 Signs, symptoms, & disease progression

Note that these signs are based on one diagnosed female patient with disease onset at 12 years old, who exhibited:

  • Muscle weakness in the neck, shoulder, and hip muscles, with difficulty rising from sitting and climbing stairs
  • Weakening of the calf and front thigh muscles
  • Wasting of the hamstring and upper back muscles
  • Contractures of the ankles (hardening and deformity of connective tissues that cause stiffness and restrict movement) may occur
  • Severely near-sighted vision
LGMD2P (LGMDR16 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2N is a rare and little studied subtype. One patient case report has noted cognitive delays.

  • Gene mutation: DAG1
  • Protein involved: dystrophin-associated glycoprotein 1
  • Age of first symptoms: undefined
LGMD2Q (LGMDR17 or z-disk proteinopathy)

An autosomal recessive subtype, LGMD2Q has some variability in its signs and symptoms across different people.

  • Gene mutation: PLEC1
  • Protein involved: plectin
  • Age of first symptoms: undefined

 Signs, symptoms, & disease progression

  • One form with later-onset progressive muscular dystrophy has also been associated with a condition that causes fragile, easily blistered skin
  • Another form with later-onset muscle weakness has been associated with problems at the junction of nerve and muscle cells
  • An early-childhood-onset form has also been identified with progressive muscular dystrophy but no associated skin problems
LGMD2R (myofibrillar myopathy or z-disk proteinopathy)

An autosomal recessive subtype, LGMD2R is caused by the same gene mutation and protein deficiency as the dominant subtype LGMD1E.

  • Gene mutation: DES
  • Protein involved: desmin
  • Age of first symptoms: early childhood – 2nd decade

Signs, symptoms, & disease progression

  • Weakness of the limb muscles closest to the body
  • Weakness of facial muscles, and a high, arched palate (roof of the mouth)
  • Breathing muscle weakness
  • Scoliosis (curving of the spine)
  • Problems with movement of electrical impulses running through the heart muscle, leading to the need for a pacemaker (an implanted device that helps regulate these impulses)
LGMD2S (LGMDR18 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2S typically first presents in early childhood.

  • Gene mutation: TRAPPC11
  • Protein involved: trafficking protein particle complex, subunit 11
  • Age of first symptoms: early childhood

Signs, symptoms, & disease progression

  • Weakness of the limb muscles closest to the body
  • Abnormally protruding shoulder blades
  • Mildly weakened facial muscles, leading to a droopy or expressionless appearance
  • Developmental delays
  • Beginning in infancy there may be involuntary movements and torso instability, possibly associated with brain problems
  • High levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged), up to 10 times normal
LGMD2T (LGMDR19 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2T can vary considerably in its age of onset and signs and symptoms across different people.

  • Gene mutation: GMPPB
  • Protein involved: GDP-mannose-pyrophosphorylase B
  • Age of first symptoms: birth – 40 years

 Signs, symptoms, & disease progression

  • Slowly progressing weakness of the limb muscles closest to the body
  • Early-onset patients may have limp, “floppy” muscles in infancy, intellectual disabilities, and occasional seizures
  • Later-onset patients may have enlarged calf muscles, muscle damage that can lead to serious kidney disease, muscle cramping, and sometimes heart problems
LGMD2U (LGMDR20 or alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2K typically first presents in early childhood.

  • Gene mutation: ISPD
  • Protein involved: isoprenoid synthase domain-containing
  • Age of first symptoms: early childhood

Signs, symptoms, & disease progression

  • Limp, “floppy” muscles
  • Muscle weakness, predominantly of the hips and thighs, causing difficulty rising from a sitting position
  • Gait disorders
  • May involve heart complications
  • High levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged), generally 3-50 times normal
LGMD2V (Pompe disease)

An autosomal recessive subtype, LGMD2V is commonly categorized as the glycogen storage disorder Pompe disease.

  • Gene mutation: GAA
  • Protein involved: alpha 1,4-glucosidase
  • Age of first symptoms: infancy – adolescence – adulthood 

Signs, symptoms, & disease progression

  • Considerable variability in age of onset and symptom severity and progression
  • The infantile-onset form is typically characterized by a weakened heart and limp, “floppy” muscles
  • The later-onset forms (adolescents and adults) is characterized by weakness of the limb muscles closest to the body, thigh muscle weakness, and breathing difficulties
LGMD2W (PINCH-2 related myopathy)

An autosomal recessive subtype, LGMD2W is characterized by severe and slowly progressing muscle weakness.

  • Gene mutation: LIMS2
  • Protein involved: lim and senescent cell antigen-like domains 2
  • Age of first symptoms: childhood

Signs, symptoms, & disease progression

  • Severe weakness of the upper and lower limb muscles closest to the body
  • Slow progression of muscle weakness
  • Distinctive features include an enlarged tongue and/or triangular in shape and enlarged calf muscles
  • Heart weakening and problems usually occur by the 20s
  • High levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged), up to 25 times normal
LGMD2X (BVES related myopathy or nuclear envelopathy)

An autosomal recessive subtype, LGMD2X is characterized by slowly progressing lower limb weakness.

  • Gene mutation: BVES
  • Protein involved: blood vessel epicardial substance
  • Age of first symptoms: adulthood

Signs, symptoms, & disease progression

  • Slowly progressing weakness of the lower limb muscles closest to the body
  • Irregular heartbeat, which may cause episodes of fainting
  • Elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)
LGMD2Y (TOR1AIP1 related myopathy or nuclear envelopathy)

An autosomal recessive subtype, LGMD2Y is characterized by slowly progressing lower limb weakness.

  • Gene mutation: TOR1AIP1
  • Protein involved: torsin A-interactin protein 1
  • Age of first symptoms: 1st – 2nd decades

Signs, symptoms, & disease progression

  • Slowly progressing weakness of the lower limb muscles closest to the body
  • Over time, weakness may also extend out to the arms and legs
  • Joint contractures (hardening and deformity of connective tissues that cause stiffness and restrict movement) in the fingers and ankles
  • A rigid spine, especially close to the neck
  • Breathing difficulties caused by restricted lung function
  • May involve mild heart problems
  • Creatine kinase (CK, an enzyme released into the blood when muscles are damaged) may be normal or elevated
LGMD2Z (alpha-dystroglycanopathy)

An autosomal recessive subtype, LGMD2Z typically first presents in early adulthood.

  • Gene mutation: POGLUT1
  • Protein involved: protein O-glucosyl-transferase 1
  • Age of first symptoms: young adulthood 

Signs, symptoms, & disease progression

  • Slowly progressing weakness of the upper and lower limb muscles closest to the body
  • Abnormally protruding shoulder blades
  • Mildly elevated levels of creatine kinase (CK, an enzyme released into the blood when muscles are damaged)

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What Is LGMD?

A group of genetic diseases that cause progressive muscle weakness…

Disease Management

urrent approaches focus on symptom management for individual patient needs…