A Guide to Meckel-Gruber Syndrome

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Meckel-Gruber syndrome, or MKS, is a rare, fatal, and genetic autosomal recessive disorder. It is named after Johann Meckel and Georg Gruber, the two people attributed to publishing the first reports of the disorder during the early 19th century.

MKS is characterized by CNS malformations, renal cystic dysplasia, pulmonary hypoplasia and polydactyly or the emergence of extra toes and fingers, among other multiple abnormalities found in organ systems. Due to severe malformations and defects caused by the disease, infants that suffer from MKS syndrome die shortly after conception or are stillborn.

Causes and genetic aspects

MKS belongs to a category of disorders called ciliopathy, which is postulated to have been caused by cilia and flagella dysfunction. The inheritance pattern is autosomal recessive and both genders are reported to be equally affected. Carriers have a 25 percent chance of conceiving affected children during each pregnancy. Furthermore, healthy siblings of the affected child have a two-thirds chance of being a carrier of the disease.

Several ongoing research ventures investigating gene mutations that cause the disease have had various results. A study on Finnish families showed that the first MKS gene’s location has been narrowed down to chromosome 17’s short arm, although the exact location and precise details are yet to be established. The malfunction of the production of novel proteins, meckelin and MKS1, have been shown as the main culprit. Studies on non-Finnish patients reportedly did not yield evidence to a gene linked to chromosome 17, so a venture was set to discover the second MKS gene. Studies on families from North Africa and the Middle East suggest the second gene’s linkage to chromosome 11’s short arm. Further research is currently undertaken to yield more evidences and specific details.

Symptoms and diagnosis

Specific malformations that arise due to the Meckel-Gruber syndrome include:

  • Polydactyly or having too many toes or fingers, or both
  • Improper development of lungs and liver prior to childbirth
  • Kidneys contain several cysts, which thus cause kidneys to be dysfunctional or too large-shaped
  • The infant’s fontanel is too large, which thus allows the protrusion of some of the spinal and brain fluid or encephalocele.
  • Some infants also have problems in the physical aspects of their genitals or faces.

Infants that suffer from the disease can be clinically diagnosed through their immediate appearance after childbirth, and employing ultrasound for symptomatic detection prior to birth during the second trimester. When the ultrasound shows that the unborn suffers from the disease, some parents choose not to push through with the pregnancy.


Neurological intervention or cardiac repair for encephalocele may be a necessary procedure for patients. Various consultations may be undertaken with a Geneticist, Pathologist, and a Perinatologist. Because no definitive cure exists, drug therapy currently does not belong to standard care procedures for the disease.