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 [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.
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.