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.
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  . 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 .
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  . 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.
- Abnormal Eye Movement
Joubert syndrome (JS) is an autosomal recessive disorder characterized by cerebellar vermis hypoplasia associated with hypotonia, developmental delay, abnormal respiratory patterns, and abnormal eye movements. [ncbi.nlm.nih.gov]
Joubert syndrome (JS; OMIM 213300) is marked by ataxia, hypotonia, abnormal eye movements, apraxia, neonatal respiratory anomalies, mental retardation, agenesis/hypoplasia of the cerebellar vermis, and a brain malformation known as the "molar tooth sign [preventiongenetics.com]
eye movements, retinal dystrophy, renal disease, ocular colobomas, and polydactyly. [invitae.com]
- Retinal Pigmentation
pigment epithelial cell line reported an association between Tctn2 depletion and the following  : Partial damage to the ciliary transition zone, a diffusion barrier involved in the regulation of both ciliogenesis and receptor localization for key [emedicine.com]
- Kidney Failure
Most often, affected infants die of respiratory problems or kidney failure. Meckel syndrome affects 1 in 13,250 to 1 in 140,000 people worldwide. [ghr.nlm.nih.gov]
Findings associated with cystic kidneys include loss of kidney function, leading to end-stage renal failure. Improper kidney function also results in a reduction in the amount of amniotic fluid surrounding the developing fetus (oligohydramnios). [rarediseases.org]
The doctors still advised me not to be too hopeful, because she would likely have kidney failure after birth and she would not be a candidate for dialysis or a kidney transplant. On October 2nd 2001, at 36 weeks I had an emergency C-section. [blogs.uwhealth.org]
- 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]
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 . 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   . 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 . Neural tube defects may be revealed by abnormal alpha-fetoprotein levels .
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  . Magnetic resonance imaging (MRI), also done prenatally, can aid diagnosis if ultrasound findings are unclear . 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.
- Occipital Encephalocele
Figure 3: Occipital encephalocele. Figure 3: Occipital encephalocele. Figure 4: Distended abdomen due to bilateral renal mass. Figure 4: Distended abdomen due to bilateral renal mass. [academic.oup.com]
In addition, an occipital encephalocele was seen. This constellation of findings is consistent with the Meckel-Gruber syndrome. [fetalsono.com]
The first child was a girl having occipital encephalocele and died at the age of one year. The second child was a boy with occipital encephalocele and died two hours after birth. [jiom.com.np]
Meckel-Gruber syndrome (MGS) is rare autosomal recessive disorder characterized by occipital encephalocele, postaxial polydactyly and polycystic kidneys. [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]
Appropriate treatment instituted in our case led to a good early outcome. [ncbi.nlm.nih.gov]
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]
Pulmonary hypoplasia is common which, together with kidney and liver disease, is responsible for the poor prognosis of most infants. [disorders.eyes.arizona.edu]
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]
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]
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]
Trends databases, including Google Trends database, can be used to estimate the digital epidemiology of these diseases. [nepjol.info]
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]
Hum Genet 1982; 62: 240–245. 15 Salonen R, Norio R : The Meckel syndrome in Finland: epidemiologic and genetic aspects. [nature.com]
Meckel–Gruber syndrome is named for Johann Meckel and Georg Gruber.    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]
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]
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- 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.