What You Should Know About Meckel-Gruber Syndrome

Meckel-Gruber syndrome, also known as dysencephalia splanchnocystica, Meckel syndrome, and Gruber syndrome, is a genetic disorder that causes a variety of severe physical defects. Because of these severe defects, those with Meckel syndrome typically die before or shortly after birth.

Genetic Mutations

Meckel syndrome is associated with an autosomal recessive mutation in at least one of 13 genes. Mutations in these eight genes account for approximately 75% of Meckel-Gruber cases. The other 25% are caused by mutations that have yet to be discovered.

In order for a child to have Meckel-Gruber syndrome, both parents must carry copies of the defective gene. If both parents carry the defective gene, there is a 25% chance their child will have the condition. There is a 50% chance that their child will inherit one copy of the gene. If the child inherits one copy of the gene, they will be a carrier of the condition. They will not have the condition themselves.

Prevalence

The incidence rate of Meckel-Gruber syndrome varies from 1 in 13,250 to 1 in 140,000 live births. Research has found that some populations, like those of Finnish descent (1 in 9,000 people) and Belgian ancestry (about 1 in 3,000 people), are more likely to be affected. Other high incidence rates have been found among among Gujarati Indians (1 in 1,300).

Despite these prevalence rates, the condition can affect any ethnic background, as well as both genders.

Symptoms

Meckel-Gruber syndrome is known for causing specific physical deformities, including:

• Enlarged kidneys with numerous fluid-filled cysts
• An abnormality called occipital encephalocele, a condition in which an infant is born with a gap in the skull (i.e., a part of one or more of the plates that form the skull does not seal). The membranes that cover the brain (meninges) and brain tissue often protrude through this gap.
• Additional fingers or toes (polydactyly)
• Heart defects
• Large kidneys full of cysts (polycystic kidneys)
  
• Liver scarring (liver fibrosis)
• Incomplete lung development (pulmonary hypoplasia)
• Cleft lip and cleft palate
• Genital abnormalities

Most Meckel-Gruber fatalities are due to respiratory problems or kidney failure.

Diagnosis

Infants with Meckel-Gruber syndrome can be diagnosed based on their appearance at birth, or by ultrasound before birth. Most cases diagnosed through ultrasound are diagnosed in the second trimester. However, a skilled technician may be able to identify the condition as early as 14 weeks into the first trimester. Molecular genetic testing can be used to confirm the diagnosis.

Treatment

Unfortunately, there is no treatment for Meckel-Gruber syndrome because the child’s underdeveloped lungs and abnormal kidneys cannot support life. Almost 100% of newborns die within days to weeks after birth. If Meckel-Gruber syndrome is detected during pregnancy, some families may choose to terminate the pregnancy.