alpha-Dystroglycanopaties
The Alpha-Dystroglycan Related Muscular Dystrophies are a group of muscular dystrophies that represent a large spectrum of neurologic and physical impairment.  Affected individuals that present in infancy are classified as having congenital muscular dystrophy (Walker-Warburg Syndrome, Muscle Eye Brain Disease and Fukuyama) and may also have brain involvement, including seizures and developmental delays.  Affected individuals that present in childhood or adulthood are classified as having limb girdle muscular dystrophy, with muscle involvement and possibly cognitive impairment.  Respiratory and cardiac involvement may also present during disease progression.  Inheritance in this group of disorders is autosomal recessive.

Video library:

The Physiology of the Alpha-Dystroglycan Related Muscular Dystrophies 

The genes involved in the dystroglycanopathies help modify a protein called alpha (α)- dystroglycan.  This modification is called glycosylation and it is necessary for the alpha (α)-dystroglycan to work. The α-dystroglycan protein helps anchor the structural framework inside each cell (cytoskeleton) to the lattice of proteins and other molecules outside the cell (extracellular matrix). In skeletal muscles, the anchoring function of α-dystroglycan helps stabilize and protect muscle fibers. In the brain, it helps direct the movement (migration) of nerve cells (neurons) during early development.

Disease
Genes
Onset
Walker-Warburg Syndrome and Muscle Eye Brain Disease
ALG13, B3GLNT2, B4GAT1, DAG1, FKRP, FKTN, GMPPB, ISPD, LARGE, POMGnT1, POMGnT2, POMT1, POMT2, RXYLT1/TMEM5
Birth
Infancy
Fukuyama Congenital Muscular Dystrophy
FKTN
Birth
Infancy
Congenital Muscular Dystrophy with or without Cognitive Impairment
DOLK, DPM1, DPM2, DPM3, FKRP, FKTN, POMT1,POMT2, POMGnT1
Birth
Infancy
Limb Girdle Muscular Dystrophy with or without Cognitive Impairment
DAG1, FKRP, FKTN, GMPPB, ISPD, POMT1, POMT2, POMGnT1, POMGnT2
Childhood or early Adulthood

Diagnosing the Alpha-Dystroglycan Related Muscular Dystrophies

To confirm a diagnosis beyond the clinical characteristics, genetic panel testing can identify which gene is affected.  Genetic panel testing involves looking for genetic mutations in genes known to cause congenital muscular dystrophy.  It is possible that the gene-causing mutations cannot be identified with current testing technology. New genes that can cause dystroglycanopathy continue to be discovered. 

In partnership with...

The Physiology of the Alpha-Dystroglycan Related Disorders

 

Walker-Warburg Syndrome

Walker-Warburg Syndrome involves genetic mutations in B3GLNT2, B4GAT1, DAG1, FKRP, FKTN, GMPPB, ISPD, or LARGE. WWS is associated with brain and eye abnormalities. Signs and symptoms are typically present at birth and include hypotonia, muscle weakness, developmental delay, intellectual disability and sometimes, seizures. WWS is also associated with lissencephaly, hydrocephalus, cerebellar malformations, eye abnormalities, and other abnormalities. Respiratory and cardiac involvement is also common. Many children do not survive beyond the age of three years.   

 

Muscle Eye Brain Disease 

Muscle Eye Brain disease involves genetic mutations in B3GLNT2, B4GAT1, DAG1, FKRP, FKTN, GMPPB, ISPD, or LARGE. Symptoms are present at birth.  Individuals with this condition are born with muscle weakness (hypotonia), severe nearsightedness (myopia), glaucoma, and brain abnormalities. They also have developmental delay and intellectual disability, a buildup of fluid in the brain (hydrocephalus), and distinctive facial features. Respiratory and cardiac involvement is also common. The prognosis for MEB varies depending on the severity of the condition. 

 

Fukuyama Congenital Muscular Dystrophy (FCMD) 

Fukuyama CMD involves mutations in the FKTN gene.  Symptoms are present at birth or in early infancy and involve poor feeding, weak muscle tone (hypotonia), droopy eyelids, muscle weakness and joint contractures.  Affected individuals experience development delays in motor skills such as sitting, standing and walking.  FCMD also affects brain development with 

delayed speech, motor skills, and moderate to severe intellectual disability.  Seizures, respiratory and cardiac complications are also common.  

 

Congenital Muscular Dystrophies with Cognitive Impairment

This group of congenital muscular dystrophies results from mutations in FKRP, LARGE, POMT1, POMT2, or POMGNT1. Symptoms can be present at birth or within the first two years of life. Symptoms may include muscle weakness, feeding difficulties, hypotonia, joint contractures and scoliosis. Motor skill delays are observed with walking achieved only in some cases.  Cognitive Impairment is present, ranging from moderate to severe retardation. Respiratory and cardiac abnormalities may also be present. 

 

Congenital Muscular Dystrophies without Cognitive Impairment

These congenital muscular dystrophies are a result of genetic mutations in FKRP or FKTN.  Symptoms can present at birth or later.  Symptoms may include muscle weakness, feeding difficulties, hypotonia, joint contractures and scoliosis. Affected individuals may have difficulty walking, difficulty climbing stairs and some will never achieve ambulation.  Respiratory and cardiac abnormalities may also be present. 

 

Limb Girdle Muscular Dystrophy: LGMDR9 FRRP Related (formerly LGMD2I), LGMDR11 POMT1 Related (formerly LGMD2K), LGMDR13 FKTN Related (formerly LGMD2M), LGMDR14 POMT2 Related (formerly LGMD2N) and LGMDR15 POMGnT1 (formerly LGMD2O), LGMDR16 DAG1 Related (formerly LGMD2P), LGMDR19 GMPPB Related (formerly LGMD2T), LGMDR20 ISPD Related (formerly LGMD2U) and LGMDR24 POMGnT2 Related (formerly known as POMGnT2).

Limb Girdle Muscular Dystrophy associated with glycosylation abnormalities involving genetic mutations in DAG1, FKRP, FKTN, GMPPB, ISPD, POMGnT1, POMGnT1, POMT1, or POMT2.  These disorders primarily involve weakness in arms and legs.  Affected individuals should be monitored for respiratory and cardiac complications. Some affected persons will have cognitive impairment.

More Resources

Connect
with Us:

Cure CMD

3217 E. Carson St. #1014
Lakewood, CA 90712 USA
+1-562-444-5656

General Inquiries:
Fundraising:

Science:

Research Grants:

About Us

Copyright © 2020 Cure CMD

Cure CMD is U.S. registered 501(c)(3) non-profit organization.
Donations are tax deductible to the extent allowable by law. 
U.S. Federal Tax ID: 26-2640975