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Meckel-Gruber Syndrome

Meckel Gruber Syndrome

Meckel-Gruber syndrome is an uncommon disorder that is inherited in an autosomal recessive pattern. It typically involves occipital encephalocele, polycystic kidneys, and postaxial polydactyly. Various additional abnormalities may occur simultaneously.


Presentation

Meckel-Gruber syndrome (MGS) is a rare autosomal recessive disorder that is the product of a number of different gene mutations and often occurs in consanguinity [1] [2]. There is no male or female preponderance. The features associated with MGS are severe and often not compatible with life resulting in intrauterine fetal death, usually due to renal failure. Also, there is an impaired amniotic fluid production and lung maturation. A minority of pregnancies are carried to term and the babies who are born with MGS rarely survive past the neonatal period, while the longest surviving case documented died at 28 months [3].

MGS chiefly affects the nervous system, kidneys, and limbs, which is mediated by defective ciliary function. The main central nervous system (CNS) manifestation is the presence of a meningoencephalocele, usually located in the occiput. Renal pathology in the form of polycystic kidneys is often the case and occurs bilaterally. Postaxial polydactyly can affect both upper and lower extremities. Individuals with MGS may also exhibit microphthalmia, cleft lip, micrognathia, liver fibrosis, gonadal dysgenesis, and congenital cardiovascular malformations such as aortic septal defect (ASD) and coarctation of the aorta [4] [5]. Moreover, there are several other congenital defects that can arise, giving MGS a more variable clinical picture. These include hydrocephalus, anencephaly, and holoprosencephaly. MGS has many genotypic features of Joubert syndrome.

Pallister-Hall Syndrome
  • L G Biesecker and J M Graham, Pallister-Hall syndrome., Journal of Medical Genetics, 10.1136/jmg.33.7.585, 33, 7, (585-589), (1996). Michael C. Summers and Alan E.[doi.org]
Saddle Nose
  • We report a fetus affected by Meckel-Gruber syndrome whose phenotype was characterized by macrocephaly, frontal bossing, a saddle nose, marked micrognathia, a distended abdomen, omphalocele, post-axial polydactyly and talipes equinovarus.[ncbi.nlm.nih.gov]
Heart Block
  • We aimed to present a fetus with Meckel-Gruber syndrome (MKS) who had left atrial isomerism, heterotaxy syndrome and complete heart block. A 26-year-old healthy female was referred to our clinic in the 23rd week of her pregnancy.[ncbi.nlm.nih.gov]
Angiomatosis
  • Von Hippel-Lindau syndrome is a different entity characterised by angiomatosis of the retina, haemangioblastoma of the cerebellum and walls of the fourth ventricle, commonly associated with polycystic lesions of the kidney and pancreas.[whonamedit.com]
Vaginal Bleeding
  • At the 32nd week, she referred to hospital with complaints of vaginal bleeding and uterine contractions. An emergency cesarean section was perfomed due to plasental malposition. A 1380 gr, female fetus was delivered.[ncbi.nlm.nih.gov]

Workup

The diagnosis of Meckel-Gruber syndrome relies on the clinical presentation. It is generally accepted that patients are diagnosed with MGS if they display a minimum of two of the most commonly occurring manifestations, that is, multicystic kidneys, occipital encephalocele, and postaxial polydactyly [6]. Other defects may also be taken into consideration during the diagnostic process, such as liver fibrosis. The characteristic features of MGS can be visualized via antenatal ultrasonography and most cases are recognized at this stage [7] [8] [9]. Early ultrasound examination is preferred (usually in the first or early second trimester), as late ultrasound scans pose a diagnostic challenge due to additional features such as oligohydramnios [8]. Neural tube defects may be revealed by abnormal alpha-fetoprotein levels [10].

Clinical diagnosis can be complicated by the presence of other disorders such as Joubert syndrome. Molecular genetic testing and karyotyping are especially useful in cases of clinical uncertainty, where the signs are atypical or masked by comorbidities. Late ultrasound findings include oligohydramnios and no visible bladder [4] [7]. Magnetic resonance imaging (MRI), also done prenatally, can aid diagnosis if ultrasound findings are unclear [11]. Although it cannot record fetal movements, MRI is effective in the detection of CNS pathology.

Karyotyping is useful in ruling out trisomy 13. Additional possible prenatal procedures include chorionic villus sampling (CVS) and amniocentesis.

Third Degree Atrioventricular Block
  • The heart rate was 46/min, consistent with third-degree atrioventricular block.[ncbi.nlm.nih.gov]
Occipital Encephalocele
  • Meckel-Gruber syndrome (MGS) is rare autosomal recessive disorder characterized by occipital encephalocele, postaxial polydactyly and polycystic kidneys.[ncbi.nlm.nih.gov]
  • Meckel-Gruber syndrome (MGS) is a rare autosomal recessive disorder which is characterized by a classic triad of occipital encephalocele, polycystic kidneys and postaxial polydactyly.[ncbi.nlm.nih.gov]
  • Each affected sib manifested only two of the three cardinal signs of MGS: occipital encephalocele and polycystic kidneys, lacking polydactyly. The phenotypic variability of the MGS pleiotropic gene is briefly discussed.[ncbi.nlm.nih.gov]
  • Meckel Gruber syndrome is a rare autosomal recessive lethal malformation characterized by typical manifestations of occipital encephalocele, bilateral polycystic kidneys and post-axial polydactyly.[ncbi.nlm.nih.gov]
  • Meckel-Gruber syndrome is a congenital disorder characterized by occipital encephalocele, polydactyly and polycystic kidneys. This rare syndrome has been reported in the literature as incompatible with life.[ncbi.nlm.nih.gov]

Treatment

  • Appropriate treatment instituted in our case led to a good early outcome.[ncbi.nlm.nih.gov]
  • Treatment Treatment Options: There is no treatment for this syndrome. The prognosis for life beyond infancy is poor due to the advanced dysfunction of numerous organs such as the kidney, lungs, liver and the central nervous system.[disorders.eyes.arizona.edu]
  • CBD Oil and Parkinson’s Disease Exercises that Ease Arthritis Proving Painsomnia is Real: A Case Study Acute Flaccid Myelitis Causes and Diagnosis Antibodies and Huntington's: Diagnosis & Treatment Advertisement Latest News WPI researchers use brain imaging[news-medical.net]
  • Treatment Unfortunately, there is no treatment for Meckel-Gruber syndrome because the child’s underdeveloped lungs and abnormal kidneys cannot support life. The condition has a 100 percent mortality rate within days of birth.[verywell.com]
  • Given the rarity of these diseases, the treatments outlined in the abstracts are not always evidence based. The information in the abstracts isnot intended to replace existing local, regional or country specific recommendations and guidelines.[orpha.net]

Prognosis

  • The prognosis is poor. The affected child is still born or dies early in infancy. If diagnosis is done by prenatal ultrasound examination termination of pregnancy can be done.[ncbi.nlm.nih.gov]
  • The parents should be counseled about prognosis of the fetus and the outcome. Counselers should strictly give information about the recurrence risk for the next pregnancies.[ncbi.nlm.nih.gov]
  • Pulmonary hypoplasia is common which, together with kidney and liver disease, is responsible for the poor prognosis of most infants.[disorders.eyes.arizona.edu]
  • Prognosis can vary if the baby has atypical signs of MGS or if the baby has a different syndrome. Elective termination of affected pregnancies may be an option for some couples. Prognosis The prognosis for MGS is quite poor.[encyclopedia.com]
  • Treatment and prognosis The condition is almost always fatal at birth either because of pulmonary hypoplasia or neonatal renal failure 3,5 . Parents can be counseled appropriately about the subsequent risk being 25%.[radiopaedia.org]

Etiology

  • A common molecular etiology appears to be disruption of ciliary TZ structure and function, affecting essential developmental signaling and the regulation of secondary messengers.[eprints.uwe.ac.uk]
  • They are organised into groups, and further divided into clinical, etiological or histopathological sub-types.[orpha.net]
  • […] category of diseases thought to be caused by dysfunction of cilia and flagella; polycystic liver and kidney disease, Bardet-Biedl syndrome, Alstrom syndrome and Joubert syndrome also belong to the same group ( Annu Rev Genomics Hum Genet 2006;7:125 ) Etiology[pathologyoutlines.com]

Epidemiology

  • We present the largest population-based epidemiological study to date using data provided by the European Surveillance of Congenital Anomalies (EUROCAT) network.[ncbi.nlm.nih.gov]
  • The Meckel syndrome in Finland: epidemiologic and genetic aspects. Am J Med Genet. 1984 Aug. 18(4):691-8. [Medline]. Salonen R. The Meckel syndrome: clinicopathological findings in 67 patients. Am J Med Genet. 1984 Aug. 18(4):671-89. [Medline].[emedicine.com]
Sex distribution
Age distribution

Pathophysiology

  • Meckel–Gruber syndrome is named for Johann Meckel and Georg Gruber. [1] [2] [3] Pathophysiology [ edit ] Meckel–Gruber syndrome (MKS) is an autosomal recessive lethal malformation. Recently, two MKS genes, MKS1 and MKS3, have been identified.[en.wikipedia.org]
  • […] live births; the live birth prevalence is significantly higher in the Finnish population (1/9,000); therefore this syndrome is suggested to be a Finnish heritage disease ( J Pediatr Neurosci 2013;8:154 ) No gender or ethnic predilection is reported Pathophysiology[pathologyoutlines.com]
  • PMID: 17389183 The role of primary cilia in the pathophysiology of neural tube defects. Vogel TW, Carter CS, Abode-Iyamah K, Zhang Q, Robinson S. Neurosurg Focus. 2012 Oct;33(4):E2. PMID: 23025443 OMIM: 213300 , 249000[bredagenetics.com]
  • The pathophysiology of MGS is complex, One study screened patients with Meckel syndrome for mutations in B9D1 and B9D2 and identified homozygous c.301A C (p.Ser101Arg) B9D2 mutation.[ncbi.nlm.nih.gov]

Prevention

  • Downstream therapeutic targeting of the Wnt5a-TMEM67-ROR2 axis might, therefore, reduce or prevent pulmonary hypoplasia in ciliopathies and other congenital conditions. 2015. Published by The Company of Biologists Ltd.[ncbi.nlm.nih.gov]
  • […] for up to one month Engineers have developed a Jell-O-like pill that quickly expands on reaching the stomach and uses an embedded sensor to monitor health status over an extended period of time. ‹ › New understanding could help improve prediction and prevention[news-medical.net]
  • Early diagnosis and proper management can prevent death at an early age. Parents should be given proper advise and genetic counselling for future management of the infants. References 1.[jiom.com.np]

References

Article

  1. Su SL, Liu CM, Lee JN. Prenatal diagnosis of Meckel-Gruber syndrome case reports. Gaoxiong Yi Xue Ke Xue Za Zhi. 1995;11(2):127–132.
  2. Smith UM, Consugar M, Tee LJ, et al. The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat Genet. 2006;38(2):191–196.
  3. Parelkar SV, Kapadnis SP, Sanghvi BV, Joshi PB, Mundada D, Oak SN. Meckel-Gruber Syndrome: a are and lethal anomaly with review of literature. J Pediatr Neurosci. 2013;8(2):154–157.
  4. Alexiev BA, Lin X, Sun CC, Brenner DS. Meckel-Gruber Syndrome: pathologic manifestations, minimal diagnostic criteria, and differential diagnosis. Arch Pathol Lab Med. 2006;130(8):1236–1238.
  5. Paavola P, Salonen R, Baumer A, et al. Clinical and genetic heterogeneity in Meckel syndrome. Hum Genet. 1997;101(1):88–92.
  6. Paavola P, Salonen R, Weissenbach J, Peltonen L. The locus for Meckel syndrome with multiple congenital anomalies maps to chromosome 17q21-q24. Nat Genet. 1995;11(2):213–215.
  7. Ickowicz V, Eurin D, Maugey-Laulom B, et al. Meckel-Gruber Syndrome: sonography and pathology. Ultrasound Obstet Gynecol. 2006;27(3):296–300.
  8. Eckmann-Scholz C, Jonat W, Zerres K, Ortiz-Brüchle N. Earliest ultrasound findings and description of splicing mutations in Meckel-Gruber Syndrome. Arch Gynecol Obstet. 2012;286(4):917–921.
  9. de Silva MV, Senanayake H, Siriwardana KD. Meckel Gruber Syndrome: Occurrence in non-consanguineous marriages. Ceylon Med J. 2004;49(1):30–31.
  10. Sepulveda W, Sebire NJ, Souka A, Snijders RJ, Nicolaides KH. Diagnosis of Meckel Gruber syndrome at eleven to fourteen weeks’ gestation. Am J Obstet Gynecol. 1997;176(2):316–319.
  11. Behairy NH, Talaat S, Saleem SN, El-Raouf MA. Magnetic resonance imaging in fetal anomalies: what does it add to 3D and 4D US? Eur J Radio. 2010;74(1):250–255.

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Last updated: 2019-06-28 10:41