Meckel syndrome

Meckel syndrome
Classification and external resources
Specialty medical genetics
ICD-10 Q61.9
OMIM 249000
DiseasesDB 31662
eMedicine ped/1390

Meckel syndrome (also known as Meckel–Gruber Syndrome, Gruber Syndrome, Dysencephalia Splanchnocystica) is a rare, lethal, ciliopathic, genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (post axial), hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.

Meckel–Gruber syndrome is named for Johann Meckel and Georg Gruber.[1][2][3]


Dysplastic kidneys are prevalent in over 95% of all identified cases. When this occurs, microscopic cysts develop within the kidney and slowly destroy it, causing it to enlarge to 10 to 20 times its original size. The level of amniotic fluid within the womb may be significantly altered or remain normal, and a normal level of fluid should not be criteria for exclusion of diagnosis.

Occipital encephalocele is present in 60% to 80% of all cases, and post-axial polydactyly is present in 55% to 75% of the total number of identified cases. Bowing or shortening of the limbs are also common.

Finding at least two of the three phenotypic features of the classical triad, in the presence of normal karyotype, makes the diagnosis solid. Regular ultrasounds and pro-active prenatal care can usually detect symptoms early on in a pregnancy.


This condition is inherited in an autosomal recessive pattern, meaning two copies of the gene in each cell are altered

Meckel–Gruber syndrome (MKS) is an autosomal recessive lethal malformation. Recently, two MKS genes, MKS1 and MKS3, have been identified. A study done recently has described the cellular, sub-cellular and functional characterization of the novel proteins, MKS1 and meckelin, encoded by these genes.[4] The malfunction of this protein production is mainly responsible for this lethal disorder.

Type OMIM Gene
MKS1 609883 MKS1
MKS2 603194 TMEM216
MKS3 607361 TMEM67
MKS4 611134 CEP290
MKS5 611561 RPGRIP1L
MKS6 612284 CC2D2A
MKS7 608002 NPHP3
MKS8 613846 TCTN2
MKS9 614144 B9D1
MKS10 611951 B9D2

Relation to other rare genetic disorders

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, Meckel–Gruber syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, and some forms of retinal degeneration.[5] The MKS1 gene has been identified as being associated with a ciliopathy.[6]


While not precisely known, it is estimated that the general rate of incidence, according to Bergsma,[7] for Meckel syndrome is 0.02 per 10,000 births. According to another study done six years later, the incidence rate could vary from 0.07 to 0.7 per 10,000 births.[8]

This syndrome is a Finnish heritage disease. Its frequency is much higher in Finland, where the incidence is as high as 1.1 per 10,000 births. It is estimated that Meckel syndrome accounts for 5% of all neural tube defects there.[9]


  1. synd/2055 at Who Named It?
  2. J. F. Meckel. Beschreibung zweier durch sehr ähnliche Bildungsabweichungen entstellter Geschwister. Deutsches Archiv für Physiologie, 1822, 7: 99–172.
  3. G. B. Gruber. Beiträge zur Frage "gekoppelter" Missbildungen (Akrocephalossyndactylie und Dysencephalia splancnocystica. Beitr path Anat, 1934, 93: 459–476.
  4. Dawe HR, Smith UM, Cullinane AR, Gerrelli D, Cox P, Badano JL, Blair-Reid S, Sriram N, Katsanis N, Attie-Bitach T, Afford SC, Copp AJ, Kelly DA, Gull K, Johnson CA (2007). "The Meckel–Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation". Human Molecular Genetics. 16 (2): 173–186. doi:10.1093/hmg/ddl459. PMID 17185389.
  5. Badano, Jose L.; Norimasa Mitsuma; Phil L. Beales; Nicholas Katsanis (Sep 2006). "The Ciliopathies : An Emerging Class of Human Genetic Disorders". Annual Review of Genomics and Human Genetics. 7: 125–148. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. Retrieved 2008-06-15.
  6. Kyttälä, Mira (May 2006). "Identification of the Meckel Syndrome Gene (MKS1) Exposes a Novel Ciliopathy" (pdf). National Public Health Institute, Helsinki. Retrieved 2008-07-06.
  7. Bergsma, D. (1979). "Birth Defects". Atlas and Compendium. London: Macmillan Press.
  8. Salonen, R.; Norio, R.; Reynolds, James F. (1984). "The Meckel syndrome: Clinicopathological Findings in 67 Patients". American Journal of Medical Genetics. 18 (4): 671–689. doi:10.1002/ajmg.1320180414. PMID 6486167.
  9. Nyberg, D. A.; et al. (1990). "Meckel–Gruber syndrome; Importance of Prenatal Diagnosis". Journal of Ultrasound Medicine. 9: 691–696.
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