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Meckel-gruber Syndrome

Disease Details

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Description: Meckel-Gruber syndrome is a rare, lethal genetic disorder characterized by renal cystic dysplasia, encephalocele, and polydactyly.
Type: Meckel-Gruber syndrome is typically transmitted in an autosomal recessive manner.
Signs And Symptoms: Meckel-Gruber syndrome, also known as Meckel syndrome, is a rare, lethal genetic disorder characterized by multiple congenital anomalies. Key signs and symptoms include:

1. **Occipital encephalocele**: A neural tube defect in which a sac-like protrusion of the brain and membranes extends through an opening in the skull.
2. **Polycystic kidneys**: Large, cyst-filled kidneys that can lead to renal failure.
3. **Postaxial polydactyly**: Extra fingers or toes.
4. **Liver fibrosis**: Abnormal fibrous tissue growth in the liver that can lead to liver dysfunction.
5. **Dandy-Walker malformation**: An abnormal development of the back part of the brain, affecting the cerebellum and the fluid spaces around it.

These congenital defects usually result in death shortly before or after birth.
Prognosis: Meckel-Gruber syndrome is a rare, lethal, autosomal recessive disorder that typically presents with a combination of renal cystic dysplasia, occipital encephalocele, and polydactyly. The prognosis is generally poor, as most affected infants are either stillborn or die shortly after birth due to complications related to these severe congenital anomalies.
Onset: Meckel-Gruber syndrome is typically characterized by its onset during the prenatal period. It is a severe congenital disorder that is usually identified through prenatal ultrasound screening due to its associated malformations.
Prevalence: The prevalence of Meckel-Gruber syndrome is estimated to be approximately 1 in 13,250 to 1 in 140,000 live births, although it can be higher in certain populations due to genetic factors.
Epidemiology: Meckel-Gruber syndrome is a rare, autosomal recessive disorder. The estimated incidence varies but is generally around 1 in 13,250 to 1 in 40,000 live births. It is more prevalent in certain populations, for example, among Finnish and Belgian populations. This syndrome frequently leads to prenatal or neonatal death, contributing to underreporting of exact prevalence.
Intractability: Meckel-Gruber syndrome is generally considered intractable. It is a rare, lethal, genetic disorder characterized by multiple congenital anomalies, including, but not limited to, renal cystic dysplasia, occipital encephalocele, and polydactyly. Most affected infants are either stillborn or die shortly after birth due to severe complications. There is currently no cure, and management focuses largely on supportive care and symptomatic treatment.
Disease Severity: Meckel-Gruber syndrome is a severe, typically lethal congenital disorder characterized by the triad of occipital encephalocele, polycystic kidneys, and polydactyly. The disease often leads to perinatal death.
Pathophysiology: Meckel-Gruber syndrome (MKS) is a rare, lethal, autosomal recessive disorder characterized by a combination of malformations. The pathophysiology of Meckel-Gruber syndrome involves defects in ciliary function, given its categorization as a ciliopathy. Primary cilia are involved in various cellular processes, including signaling pathways crucial for development. Mutations in genes responsible for cilia structure and function (such as MKS1, TMEM67, and CC2D2A) lead to impaired cilia, resulting in the syndrome's characteristic anomalies. These include encephalocele, polycystic kidneys, hepatic fibrosis, and polydactyly. The disruption in the normal function of the cilia affects multiple organ systems, leading to the severe manifestations observed in MKS.
Carrier Status: Carrier status describes an individual who carries one altered copy of a gene associated with an autosomal recessive disorder, like Meckel-Gruber syndrome, but does not show symptoms of the disease because they have one normal copy of the gene.
Mechanism: Meckel-Gruber syndrome (MKS) is a rare, lethal autosomal recessive disorder characterized by renal cystic dysplasia, occipital encephalocele, and polydactyly. The syndrome results from mutations in genes involved in the primary cilium, a cellular organelle that plays a crucial role in various signaling pathways.

**Molecular Mechanisms:**

1. **Ciliopathy:** Mutations in genes associated with Meckel-Gruber syndrome (e.g., MKS1, TMEM216, TMEM67, CC2D2A) disrupt the structure and function of primary cilia. These cilia are essential for various signaling pathways, including those regulating cell differentiation, tissue maintenance, and embryonic development.

2. **Signal Transduction Disruption:** The primary cilium acts as a hub for several signaling pathways, including Hedgehog (Hh), Wnt, and PDGF. Mutations in MKS genes lead to defective signaling cascades, causing abnormal tissue development and organogenesis.

3. **Cell Cycle and Apoptosis:** Ciliary defects can alter the cell cycle and increase apoptosis, particularly in the developing kidney and brain, contributing to renal cysts and encephaloceles.

4. **Basal Body Dysfunction:** Many MKS proteins localize to the basal body, the anchoring point for primary cilia. Mutations can impair basal body function, preventing the proper assembly and maintenance of cilia.

Together, these molecular disruptions underscore the pathogenesis of Meckel-Gruber syndrome, leading to the characteristic anomalies seen in affected individuals.
Treatment: Meckel-Gruber syndrome is a rare, lethal, genetic disorder with no available cure. Treatment primarily focuses on supportive care and managing symptoms. Due to its severity, prenatal diagnosis often leads to counseling and consideration of pregnancy options. Postnatal care is typically centered around providing comfort measures for the affected infant.
Compassionate Use Treatment: Meckel-Gruber syndrome is a rare genetic disorder, and there are currently no established cures or specific treatments for it. Management primarily focuses on symptomatic and supportive care, often involving a multidisciplinary team.

**Compassionate Use Treatment:**
Compassionate use treatment, also known as expanded access, allows patients with serious or life-threatening conditions to gain access to investigational drugs or treatments that have not yet been approved by regulatory agencies like the FDA. For Meckel-Gruber syndrome, compassionate use might involve enrolling in clinical trials or accessing experimental therapies, though these options are generally limited due to the rarity and severity of the syndrome.

**Off-label or Experimental Treatments:**
As of now, there are no well-documented off-label treatments specifically for Meckel-Gruber syndrome. Experimental treatments would likely be in the realm of genetic research, aiming to better understand and potentially correct the genetic mutations involved. Gene therapy and CRISPR-based technologies are areas of active research that might hold future potential, although they are currently not available as standard treatments.

Supportive care includes addressing the individual symptoms such as managing renal issues, addressing liver fibrosis, and possibly surgical interventions for associated anatomical abnormalities. Genetic counseling is also recommended for affected families.
Lifestyle Recommendations: Meckel-Gruber syndrome is a rare, genetic disorder that usually presents significant complications and is often fatal shortly after birth. Due to its severe nature, specific lifestyle recommendations are generally not applicable. Supportive care and prenatal counseling are key aspects for families affected by this condition. Prenatal diagnosis through genetic testing and imaging can help in early detection and planning. Families may benefit from the support of a genetic counselor and healthcare team to understand their options and manage the emotional and medical challenges associated with this syndrome.
Medication: Meckel-Gruber syndrome is a rare, genetic, fatal disorder that typically results in death shortly after birth. There is no specific medication for treating Meckel-Gruber syndrome. Management of the condition often focuses on supportive care and symptom management. Genetic counseling is recommended for affected families.
Repurposable Drugs: Currently, there are no repurposable drugs identified for Meckel-Gruber syndrome. Research into potential treatments is ongoing, but as of now, management focuses on supportive care and symptom management.
Metabolites: Meckel-Gruber syndrome is a rare, fatal genetic disorder. Due to its complex nature and a lack of comprehensive metabolic profiling in current scientific literature, specific metabolite data for Meckel-Gruber syndrome is not well-established or readily available (hence, "nan" for not applicable/available). The syndrome primarily affects the development of multiple organ systems, particularly the central nervous system and kidneys, often leading to perinatal death. If you need information on particular metabolic abnormalities associated with this syndrome or related research, a specialist in genetic metabolic disorders or a review of the most recent scientific research might be needed.
Nutraceuticals: There are no known nutraceuticals that have been proven to treat or mitigate Meckel-Gruber Syndrome. This is a rare, genetic disorder characterized by a combination of anomalies such as encephalocele, polycystic kidneys, and polydactyly. Management primarily involves supportive care and symptomatic treatment after thorough medical evaluation.
Peptides: Meckel-Gruber syndrome is a rare genetic disorder that typically leads to severe developmental anomalies such as encephalocele, polycystic kidneys, and polydactyly. There is limited specific information on peptides directly related to Meckel-Gruber syndrome. Further scientific research is necessary to outline any particular peptides involved in the pathophysiology of this condition. If you're looking for genomic or proteomic insights, consulting recent scientific literature or specialized databases would be advisable.