What Is Meckel-Gruber Syndrome?

Meckel-Gruber syndrome is a fatal genetic condition

Newborn Babies
Newborn Babies. Dan Kitwood / Staff / Getty Images

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

The Genes Behind Meckel-Gruber Syndrome

Meckel syndrome is associated with a mutation in at least one of eight genes.

Mutations in these eight genes account for approximately 75-percent of Meckel-Gruber cases. The other 25 percent 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-percent chance their child will have the condition. There is a 50-percent 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.

The Rarity of the Disease

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 the Bedouins in Kuwait (1 in 3,500) and among Gujarati Indians (1 in 1,300).

These populations also have high carrier rates, with anywhere from 1 in 50 to 1 in 18 people carrying a copy of the defective genes. Despite these prevalence rates, the condition can affect any ethnic background, as well as both genders.

Common Symptoms of Meckel-Gruber Syndrome

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

  • A large front soft spot (fontanel), which allows some of the brain and spinal fluid to bulge out (encephalocele)
  • Heart defects
  • Large kidneys full of cysts (polycystic kidneys)
  • Additional fingers or toes (polydactyly)
  • Liver scarring (liver fibrosis)
  • Incomplete lung development (pulmonary hypoplasia)
  • Cleft lip and cleft palate
  • Genital abnormalities

Cystic kidneys are the most common symptom, followed by polydactyly. Most Meckel-Gruber fatalities are due to pulmonary hypoplasia, incomplete lung development.

Diagnosis Through Appearance and Chromosome Analysis

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 during the first trimester. Chromosome analysis, either through chorionic villus sampling or amniocentesis, can be done to rule out Trisomy 13, an almost equally fatal condition with similar symptoms.

Treatment

Unfortunately, there is no treatment for Meckel-Gruber syndrome because the child’s underdeveloped lungs and abnormal kidneys cannot support life. The condition has a 100 percent mortality rate within days of birth. If Meckel-Gruber syndrome is detected during pregnancy, some families may choose to terminate the pregnancy.

Sources:

Carter, S.M. (2015). Meckel-Gruber syndrome. eMedicine.

NIH Genetics Home Reference. Meckel Syndrome (2016)

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