Meckel-Gruber syndrome (MKS) is a rare, lethal, autosomal recessive genetic disorder characterized by a specific combination of malformations, most notably occipital encephalocele, bilateral polycystic kidneys, and postaxial polydactyly.
Key Features of Meckel-Gruber Syndrome
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Occipital Encephalocele: This involves a sac-like protrusion of the brain through an opening in the back of the skull (occipital region). The sac may contain brain tissue and cerebrospinal fluid.
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Bilateral Polycystic Kidneys: Both kidneys are affected by the formation of numerous cysts, which disrupt normal kidney function. This typically leads to kidney failure.
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Postaxial Polydactyly: The presence of extra fingers or toes located on the side of the hand or foot furthest from the thumb or big toe, respectively.
Other Possible Features
While the three features above are considered the cardinal signs, individuals with MKS can also exhibit other abnormalities, including:
- Central Nervous System: Microcephaly, hydrocephalus, agenesis of the corpus callosum, and other brain malformations.
- Facial Abnormalities: Cleft lip and/or palate, micrognathia (small jaw), and other facial dysmorphisms.
- Skeletal Abnormalities: Rib abnormalities, limb shortening, and other skeletal defects.
- Liver Abnormalities: Hepatic fibrosis and bile duct proliferation.
- Genital Abnormalities: Ambiguous genitalia.
- Eye Abnormalities: Abnormalities within the eye itself.
Inheritance and Incidence
Meckel-Gruber syndrome is inherited in an autosomal recessive pattern. This means that both parents must carry a copy of the mutated gene for their child to be affected. If both parents are carriers, there is a 25% chance with each pregnancy that the child will inherit the disorder.
The worldwide incidence of MKS varies, ranging from approximately 1 in 13,250 to 1 in 140,000 live births. Certain populations, such as those with higher rates of consanguinity (marriage between close relatives), may have a higher incidence.
Diagnosis and Prognosis
Diagnosis is typically based on ultrasound findings during pregnancy or physical examination after birth. Genetic testing can confirm the diagnosis.
The prognosis for individuals with MKS is very poor. Due to the severity of the malformations, particularly the kidney and brain abnormalities, most affected infants die shortly before or after birth.
