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.

• Coarctation of the Aorta

  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. [symptoma.com]

  Other anomalies include microcephaly, microphthalmia or anophthalmia, cleft lip and/or palate, genital anomalies, lung hypoplasia, and congenital heart disease such as atrial septal defect (ASD), ventricular septal defect (VSD), coarctation of the aorta [accessanesthesiology.mhmedical.com]

  Cardiac lesions like atrial septal defect, coarctation of the aorta and pulmonary stenosis may be present [ 7, 8 ]. Worldwide, the incidence of Meckel-Gruber syndrome is 1 per 13,250–140,000 live births. [ncbi.nlm.nih.gov]

• Bowing of The Long Bones

  Additional skeletal malformations include bowing of the long bones of the arms and legs, curvature of the fifth fingers (clinodactyly), webbing of the fingers and toes (syndactyly), and club foot where the foot are rotated internally (talipes equinovarus [rarediseases.org]

• Suggestibility

  USG abdomen was suggestive of bilateral multicystic dysplastic kidneys [Figure 3]. Computerized tomography (CT) brain was suggestive of large occipital encephalocele with normal ventricles [Figure 4]. [ncbi.nlm.nih.gov]

  Together, these data suggest that defective cilia loading, but not a global loss of ciliogenesis, basal body docking or PCP signaling leads to dysfunctional cilia in MKS3 tissues. [mayoclinic.pure.elsevier.com]

• Kidney Failure

  Prognosis MKS is lethal in utero or in the very early neonatal period with pulmonary hypoplasia and kidney failure as the main causes of early demise. * European Reference Network The documents contained in this web site are presented for information [orpha.net]

  […] fatalities are due to respiratory problems or kidney failure. [verywellhealth.com]

  Most often, affected infants die of respiratory problems or kidney failure. 2. Frequency Meckel syndrome affects 1 in 13,250 to 1 in 140,000 people worldwide. [encyclopedia.pub]

  Most often, affected infants die of respiratory problems or kidney failure. Frequency Meckel syndrome affects 1 in 13,250 to 1 in 140,000 people worldwide. [medlineplus.gov]

  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]

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.

• Multiple Renal Cysts

  Meckel-Gruber syndrome (MGS) is classically characterized by the triad of: renal cystic dysplasia : multiple renal cysts (present most cases) occipital encephalocoele / holoprosencephaly (~70%) postaxial polydactyly : usually hexadactyly (~65%) Additional [radiopaedia.org]

• Occipital Encephalocele

  In addition, an occipital encephalocele was seen. This constellation of findings is consistent with the Meckel-Gruber syndrome. [fetalsono.com]

  Keywords: Encephalocele, Meckel-Gruber syndrome, polycystic kidney, polydactyly Introduction Meckel-Gruber syndrome (MGS) is a triad of occipital encephalocele, large polycystic kidneys, and postaxial polydactyly. [ncbi.nlm.nih.gov]

  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]

  J Pediatr Neurosci 2013;8:154-7 Meckel-Gruber syndrome (MGS) is a triad of occipital encephalocele, large polycystic kidneys, and postaxial polydactyly. [pediatricneurosciences.com]

  The occipital encephalocele usually comes through an apical defect of the occipital bone or enlarged posterior fontanelle. Often a second, smaller defect of the basal occipital bone is found with or without another meningocele. [ruralneuropractice.com]

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]

Management and treatment No treatment is currently available for Meckel syndrome which has a constantly fatal outcome. [orpha.net]

Appropriate treatment instituted in our case led to a good early outcome. [ncbi.nlm.nih.gov]

The adult phenotype will be characterized and chaperone treatment tested. [grantome.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]

What is the prognosis for an individual with an MKS1-related Disorder? Meckel-Gruber syndrome is a lethal condition, and prognosis is poor. Those affected are either stillborn or die in the first few hours or days of life. [myriad.com]

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]

TMEM67 mutation (MKS3) is a major cause of MKS and the related ciliopathy Joubert syndrome, although the complete etiology of the disease is not well understood. [mayoclinic.pure.elsevier.com]

A more indolent presentation characterized by abdominal pain of unclear etiology will often be evaluated over the course of weeks to months. [visualdx.com]

In recent years, the molecular etiology of the diseases in the ciliopathic group has been elucidated owing to the widespread use of next-generation sequencing technology. [liebertpub.com]

Etiology Defective ciliary biology underlies MKS. Mutations in many different cilia-related genes have been associated with this disorder, often in the context of consanguineous unions. [orpha.net]

Overall this study will contribute major insight into the etiology and pathogenicity of recessive forms of PKD, and provide clues for therapeutics. [grantome.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]

There is a shortage of epidemiological studies surveying the region of the Middle East and Arabic countries. [ccsenet.org]

Pathophysiology It has been suggested that a failure of mesodermal induction causes MKS. The induction cascades of early morphogenesis involve numerous growth factors, homeobox genes, and paired domain genes. [accessanesthesiology.mhmedical.com]

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]

Etiology and Pathophysiology Several genetic loci have been identified in individuals with Meckel-Gruber syndrome. The disorder is caused by dysfunction of primary cilia during embryogenesis. [radiologykey.com]

140,000 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]

Prevention How Is Meckel Syndrome Prevented? There is no known way to prevent Meckel syndrome. [unitedbrainassociation.org]

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]

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]

[…] 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]

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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.
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