Meckel–Gruber syndrome

Embryos with mutation in Mks1krc, a cause of Meckel syndrome

Meckel–Gruber syndrome

Meckel–Gruber syndrome (MKS), also known as Meckel syndrome, is a rare, lethal, autosomal recessive genetic disorder characterized by a combination of renal cystic dysplasia, occipital encephalocele, and polydactyly. The syndrome is named after the German anatomist Johann Friedrich Meckel and the Swiss pathologist George Gruber.

Clinical Features

The primary features of Meckel–Gruber syndrome include:

• Renal cystic dysplasia: Abnormal development of the kidneys with the presence of multiple cysts.
• Occipital encephalocele: A neural tube defect where brain tissue protrudes through an opening in the skull.
• Polydactyly: The presence of extra fingers or toes.

Other associated anomalies may include hepatic fibrosis, central nervous system malformations, cleft lip and palate, and genital anomalies.

Genetics

Meckel–Gruber syndrome is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. Several genes have been implicated in MKS, including MKS1, MKS2, MKS3, and others. These genes are involved in the development and function of cilia, which are hair-like structures on the surface of cells that play a crucial role in cell signaling and tissue development.

Diagnosis

The diagnosis of Meckel–Gruber syndrome is typically made based on clinical features and confirmed by prenatal ultrasound or genetic testing. Prenatal ultrasound can detect characteristic features such as renal cysts, encephalocele, and polydactyly.

Management

There is no cure for Meckel–Gruber syndrome, and management is primarily supportive. Due to the severe nature of the condition, most affected pregnancies result in stillbirth or neonatal death. Genetic counseling is recommended for families with a history of MKS to discuss the risks of recurrence in future pregnancies.

Epidemiology

Meckel–Gruber syndrome is a rare disorder, with an estimated incidence of 1 in 13,250 to 1 in 140,000 live births. It is more common in certain populations, such as the Finnish and Gujarati Indian communities.

See Also

• Genetic disorder
• Autosomal recessive inheritance
• Renal cystic dysplasia
• Occipital encephalocele
• Polydactyly
• Prenatal diagnosis
• Genetic counseling