Meckel syndrome

Meckel syndrome (also known as Meckel-Gruber syndrome, MKS, or dysencephalia splanchnocystica) is a severe, lethal autosomal recessive ciliopathy characterized by a classic triad of findings: bilateral renal cystic dysplasia, occipital encephalocele, and postaxial polydactyly. It is one of the most common syndromic forms of neural tube defect. The condition affects multiple organ systems, with the kidneys being the most consistently involved feature (present in nearly 100% of cases). The occipital encephalocele occurs in approximately 60-80% of cases, and polydactyly is seen in about 55-75% of cases. Additional features may include hepatic ductal plate malformation (hepatic fibrosis and bile duct proliferation), pulmonary hypoplasia, cleft lip and palate, cardiac defects, genital anomalies, and central nervous system malformations such as Dandy-Walker malformation and holoprosencephaly. Meckel syndrome is genetically heterogeneous, with pathogenic variants identified in at least 16 genes (including MKS1, TMEM216, TMEM67, CEP290, RPGRIP1L, CC2D2A, NPHP3, TCTN2, B9D1, B9D2, TMEM231, KIF11, TMEM107, NPHP4, CSPP1, and TXNDC15), all of which encode proteins involved in the structure or function of primary cilia or the basal body. This places Meckel syndrome within the broader spectrum of ciliopathies, which includes related but less severe conditions such as Joubert syndrome and Bardet-Biedl syndrome. Diagnosis can often be made prenatally through ultrasound imaging, typically in the second trimester, revealing the characteristic combination of cystic kidneys, encephalocele, and polydactyly. Meckel syndrome is uniformly lethal, with most affected infants being stillborn or dying within hours to days after birth, primarily due to pulmonary hypoplasia and renal failure. There is currently no curative treatment or disease-modifying therapy available. Management is limited to supportive and palliative care. Genetic counseling is essential for affected families, as the recurrence risk is 25% with each pregnancy. Prenatal diagnosis and preimplantation genetic testing are available for families with a known molecular diagnosis.

Common questions about Meckel syndrome