Overview
- Meckel-Gruber Syndrome (MKS) is a lethal, autosomal recessive neurodevelopmental condition characterized by a triad of symptoms which are occipital encephalocele, large polycystic kidneys and postaxial polydactyly. It is caused by mutations in genes encoding proteins that allow an appropriate structure and function of the primary cilium. It belongs to a group of diseases known as ciliopathies, and since cilia are present in a variety of organs in the human organism it has several other manifestations. Associated abnormalities include oral clefting, genital anomalies, CNS alterations and liver fibrosis. The leading cause of death is pulmonary hypoplasia.
- The Igenomix Meckel-Gruber Syndrome Precision Panel can be used to make a directed and accurate diagnosis ultimately leading to a better management and prognosis of the disease. It provides a comprehensive analysis of the genes involved in this disease using next-generation sequencing (NGS) to fully understand the spectrum of relevant genes involved.
Indication
- The Igenomix Meckel-Gruber Syndrome Precision Panel is indicated for those patients with a clinical suspicion or diagnosis of Meckel-Gruber Syndrome presenting with:
- CNS abnormalities: occipital encephalocele, Dandy-Walker malformation, hydrocephalus, Arnold-Chiari malformation, microcephaly
- Polycystic kidneys
- Polydactyly
- Hepatic fibrosis
- Cardiac malformations: atrial septal defect, coarctation of aorta and pulmonary stenosis
- Cleft lip and palate
- Genital anomalies
Clinical Utility
The clinical utility of this panel is:
- The genetic and molecular confirmation for an accurate clinical diagnosis of a symptomatic patient.
- Early initiation of treatment with a multidisciplinary team in the form of surgical repair of anatomic abnormalities.
- Risk assessment of asymptomatic family members according to the mode of inheritance.
- Improvement of delineation of genotype-phenotype correlation.
References
Hartill, V., Szymanska, K., Sharif, S. M., Wheway, G., & Johnson, C. A. (2017). Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances. Frontiers in pediatrics, 5, 244. https://doi.org/10.3389/fped.2017.00244
Radhakrishnan, P., Nayak, S. S., Shukla, A., Lindstrand, A., & Girisha, K. M. (2019). Meckel syndrome: Clinical and mutation profile in six fetuses. Clinical genetics, 96(6), 560–565. https://doi.org/10.1111/cge.13623
Szymanska, K., Hartill, V. L., & Johnson, C. A. (2014). Unraveling the genetics of Joubert and Meckel-Gruber syndromes. Journal of pediatric genetics, 3(2), 65–78. https://doi.org/10.3233/PGE-14090
Khurana, S., Saini, V., Wadhwa, V., & Kaur, H. (2017). Meckel-Gruber syndrome: ultrasonographic and fetal autopsy correlation. Journal of ultrasound, 20(2), 167–170. https://doi.org/10.1007/s40477-016-0231-4
Smith, U., Consugar, M., Tee, L., McKee, B., Maina, E., & Whelan, S. et al. (2006). The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nature Genetics, 38(2), 191-196. doi: 10.1038/ng1713
Magann, E., Haas, D., Hill, J., Chauhan, S., Watson, E., & Learman, L. (2011). Oligohydramnios, Small for Gestational Age and Pregnancy Outcomes: An Analysis Using Precise Measures. Gynecologic And Obstetric Investigation, 72(4), 239-244. doi: 10.1159/000324570
Barker, A. R., Thomas, R., & Dawe, H. R. (2014). Meckel-Gruber syndrome and the role of primary cilia in kidney, skeleton, and central nervous system development. Organogenesis, 10(1), 96–107. https://doi.org/10.4161/org.27375
