Meckel-Gruber Syndrome
Overview
Meckel-Gruber Syndrome (MKS) is a rare, lethal, genetic, multisystem disorder characterized by the presence of occipital encephalocele, cystic kidneys, and polydactyly. It is an autosomal recessive disorder, meaning that both parents must carry and pass on the defective gene for a child to be affected. The syndrome is named after Johann Friedrich Meckel and Georg Bartsch Gruber, who first described the condition in the 19th century.
Clinical Features
The clinical features of MKS are variable and can include numerous abnormalities. The three primary characteristics are encephalocele, polycystic kidney disease, and polydactyly. Other features can include cleft lip/palate, liver fibrosis, and anomalies in the genitalia.
Encephalocele
An encephalocele is a neural tube defect characterized by sac-like protrusions of the brain and the membranes that cover it through openings in the skull. In MKS, the encephalocele is typically occipital, meaning it is located at the back of the skull.
Polycystic Kidney Disease
Polycystic kidney disease in MKS is characterized by the presence of numerous cysts in the kidneys. These cysts are filled with fluid and can cause the kidneys to become enlarged. This can lead to kidney failure at an early age.
Polydactyly
Polydactyly is a condition in which a person is born with more than the usual number of fingers or toes. In MKS, polydactyly is often seen, and the extra digits are usually postaxial, meaning they are on the little finger side of the hand or the little toe side of the foot.
Genetics
MKS is an autosomal recessive disorder, which means that both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
MKS is caused by mutations in several different genes, including MKS1, MKS3, and others. These genes are involved in the formation and function of cilia, which are tiny, hair-like structures that project from the surface of cells and are involved in cell movement and signaling.
Diagnosis
Diagnosis of MKS is based on clinical features and can be confirmed by genetic testing. Prenatal diagnosis is possible through ultrasound examination and can be confirmed by genetic testing if the causative mutations are known.
Management and Prognosis
There is currently no cure for MKS, and management is supportive. The prognosis for individuals with MKS is poor, with most infants dying shortly after birth due to respiratory difficulties or kidney failure.
Epidemiology
MKS 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 population, due to a founder effect.