What Are POMGNT1-Related Disorders?
POMGNT1-related disorders include multiple conditions known as muscular dystrophy-dystroglycanopathies (MDDG). The various POMGNT1-related disorders, which are caused by mutations in the POMGNT1 gene, are described below in the order of severity.
Muscular Dystrophy-Dystroglycanopathy Type A3 (MDDGA3)
MDDGA3 includes POMGNT1-related Walker-Warburg syndrome (WWS) and muscle-eye-brain disease (MEB). These POMGNT1-related disorders are characterized by significant and progressive muscle weakness, vision problems, changes in brain structure, and severe intellectual and developmental disabilities. In infancy, the child may feel floppy when held. In childhood, the development of motor skills is affected, with many children being unable to sit or walk independently. A wide range of eye problems may be seen in children with MDDGA3, including severe near-sightedness, glaucoma, cataracts, and changes in the retina. As a result, significant vision impairment is common. With both WWS and MEB, changes in the brain are characteristic, including a buildup of fluid around the brain (hydrocephalus) and underdevelopment of the brainstem. A hallmark of WWS, but which may also be seen in MEB, is a brain abnormality known as cobblestone lissencephaly (or type II lissencephaly), where the brain develops a bumpy “cobblestone” appearance and lacks the normal folding structure. Individuals with MDDGA3 may also experience seizures, and significant intellectual disability is expected. The severity of symptoms varies, but most individuals with MDDGA3 are severely affected and their lifespans are significantly shortened.
Muscular Dystrophy-Dystroglycanopathy Type B3 (MDDGB3)
Individuals with MDDGB3, which may also be referred to as POMGNT1-related Fukuyama congenital muscular dystrophy (FCMD), experience significant and progressive muscle weakness, although it is generally less severe than with MDDGA3. Some individuals may eventually be able to walk, while others may not. The eye problems in individuals with MDDGB3 are variable, but they also tend to be milder than seen with MDDGA3. In addition, developmental delays, moderate intellectual disability, seizures, and brain changes of variable severity are common among those with this POMGNT1-related disorder.
Muscular Dystrophy-Dystroglycanopathy Type C3 (MDDGC3)
MDDGC3 is also referred to as limb-girdle muscular dystrophy (LGMD) type 2O. LGMD2O is the mildest of the POMGNT1-related disorders, and both age of onset and severity of symptoms vary greatly among individuals with this condition. Typically, the only symptom is weakness in the muscles closest to the center of the body, specifically the muscles of the shoulders, upper arms, pelvic area, and thighs. However, the weakness is progressive and may affect mobility. The brain and eyes are not affected in those with LGMD2O, and both intelligence and lifespan are typically normal.
How Common Are POMGNT1-Related Disorders?
The exact prevalence of POMGNT1-related disorders is unknown, although these conditions are considered rare. Certain subtypes, however, may be more common in specific populations. For example, MEB appears to be more common in the Finnish population, where the prevalence is 1 in 50,000.
How Are POMGNT1-Related Disorders Treated?
There is no treatment for the underlying cause of POMGNT1-related disorders. Available treatments address only the symptoms of the condition, such as physical and occupational therapy to improve motor skills and mobility, vision services and glasses to treat eye problems, and the use of medication to control seizures.
What Is the Prognosis for a Person with a POMGNT1-Related Disorder?
The prognosis for an individual with a POMGNT1-related disorder varies depending on the severity of the condition. Most individuals with WWS and MEB (MDDGA3) have severe vision loss and intellectual disability, and lifespan is significantly shortened. Individuals with FCMD (MDDGB3) also tend to have significant complications that result in a shortened lifespan. In contrast, those with LGMD2O (MDDGC3) are expected to have normal intelligence and a normal lifespan.