Meckel-Gruber Syndrome: Characteristics and Prospective Survival
Meckel-Gruber syndrome is a rare, genetic disorder that affects approximately 1 in 13,250 to 1 in 140,000 live births worldwide. This condition is characterized by a variety of developmental problems and affects several organs and systems, including the face and head, heart, lungs, liver, genitourinary tract, and eyes.
The outlook for babies born with Meckel-Gruber syndrome is poor, with problems in the brain, lungs, and kidneys leading to death in 100% of cases. The typical life expectancy is measured in days or weeks. However, it's important to note that mental-health support services, such as counseling and case management, can be beneficial for parents in coping with the stress, grief, and other emotions that come with this diagnosis. Most hospitals have mental-health support staff, counselors, and case managers to help families find the support they need.
Meckel-Gruber syndrome is caused by mutations in multiple cilia-related genes, making it a ciliopathy. The syndrome is genetically heterogeneous, with around 14 known disease genes involved. The most common individual gene mutations are C5orf42 (12%), TMEM67 (10%), and AHI1 (8%). TMEM67 gene mutations contribute significantly, accounting for around 10% in Meckel-Gruber and 70% in related COACH syndrome, implying a major role in about 75% of cases when considering combined gene involvement.
Meckel-Gruber syndrome is an autosomal recessive disorder, meaning a fetus needs to receive a copy of a variant gene from each parent to acquire the condition. The condition has an equal chance of occurring in males and females. When two parents have the recessive gene, a baby has a 25% chance of inheriting the disorder. The odds do not increase or decrease with additional children. In some cases, the cause of Meckel-Gruber syndrome is unknown.
Some populations have a higher likelihood of occurrence, such as Finnish, Belgian, and Gujarati Indian populations. Diagnosis can occur prior to birth through ultrasound and genetic testing. If prenatal testing indicates Meckel-Gruber syndrome, parents may choose to terminate the pregnancy with guidance from genetic counselors and healthcare staff.
Meckel-Gruber syndrome was first recorded by Johann Friedrich Meckel in 1822 and was later named dysencephalia splanchnocystica by Meckel. The disorder is passed down to a child in utero when both parents have the recessive gene alteration. Meckel-Gruber syndrome may be a particularly severe form of Joubert syndrome.
Current treatment cannot cure or correct Meckel-Gruber syndrome, and it is always fatal. Treatment is typically supportive and addresses symptoms. It's crucial for parents and healthcare providers to work together to provide the best care possible for affected babies during their short lives.
[1] Genetics Home Reference. (2021). Meckel-Gruber syndrome. Retrieved March 15, 2023, from https://ghr.nlm.nih.gov/condition/meckel-gruber-syndrome [3] OMIM. (2023). MECKEL-GRUBER SYNDROME. Retrieved March 15, 2023, from https://omim.org/entry/249000
- Despite the poor prognosis of Meckel-Gruber syndrome, mental-health support services can offer immense help for parents navigating through such challenging circumstances.
- Meckel-Gruber syndrome is categorized under ciliopathies, a group of conditions caused by mutations in multiple cilia-related genes.
- The condition, which is genetically heterogeneous, involves around 14 known disease genes, with C5orf42, TMEM67, and AHI1 being the most common individual gene mutations.
- Meckel-Gruber syndrome is an autosomal recessive disorder, with each parent contributing a variant gene for the fetus to develop the condition, and equally impacting males and females.
- Some populations, including Finnish, Belgian, and Gujarati Indian populations, are observed to have a higher likelihood of occurrence.
- While there is no cure for Meckel-Gruber syndrome, proper management focusing on alleviating symptoms is crucial to provide the best possible care during the child's short life, emphasizing collaboration between parents and healthcare providers.
