Scientific Medical Center of Obstetrics and Gynecology, Republic of Uzbekistan
Definition
Meckel syndrome, also known as Meckel-Gruber syndrome, is a severe pleiotropic autosomal recessive developmental disorder caused by dysfunction of primary cilia during early embryogenesis. The classic triad of Meckel syndrome comprises:
- cystic renal disease;
- central nervous system malformation, most commonly occipital encephalocele;
- polydactyly, most often postaxial.
Synonyms
Dysencephalia splanchnocystica.
Diagnostic criteria
There is extensive clinical variability and controversy as to the minimum diagnostic criteria.
Early reports, including that of Opitz and Howe, [4] and Wright et al. [7], stated that the classic triad of Meckel syndrome comprises:
- cystic renal disease;
- central nervous system malformation, most commonly occipital encephalocele;
- polydactyly, most often postaxial.
However, based on a study of 67 patients, Salonen [5] concluded that the minimum diagnostic criteria are:
- cystic renal disease;
- central nervous system malformation,
- hepatic abnormalities, including portal fibrosis or ductal proliferation.
In a review of Meckel syndrome, Logan et al. [4] stated that the classic triad first described by Meckel [1] included
- occipital encephalocele;
- cystic kidneys;
- fibrotic changes of the liver.
History
The first reports of Meckel-Gruber syndrome were published in 1822 by Johann Friedrich Meckel [1]. G. B. Gruber also published reports of patients with Meckel-Gruber syndrome in 1934 and gave it the name dysencephalia splanchnocystica. Meckel-Gruber syndrome is also known as Meckel syndrome and Gruber syndrome [2].
The triad of occipital encephalocele, large polycystic kidneys, and postaxial polydactyly characterizes Meckel-Gruber syndrome. Majewski et al. [3] concluded that sometimes the polydactyly in Meckel syndrome is preaxial and that bowing of the long bones of the limbs occurs in about one-sixth of cases.
Associated abnormalities
Oral clefting, genital anomalies, central nervous system malformations, including Dandy-Walker and Arnold-Chiari malformation, hepatic fibrosis, micrognathia, hypopituitarism, cardiac and genital anomalies, short-webbed neck, accessory spleens, syndactyly, clinodactyly, clubbed feet.
Prevalence
The incidence of Meckel-Gruber syndrome varies from 0.07 - 0.75 : 10,000 births. Meckel-Gruber syndrome occurs in all ethnicities although there is increased incidence reported in the Belgian population (3.3 : 10,000), the Finnish population (1.1 : 10,000), and the Ashkenazi Jewish population (0.2 : 10,000). Males and females are affected equally. It is estimated that Meckel-Gruber syndrome accounts about 5% of all neural tube defects.
Etiology
Meckel-Gruber syndrome (OMIM 24900) is a lethal, rare, autosomal recessive condition mapped to 6 different loci in chromosomes 17q21-24 (MKS1), 11q13 (MKS2), 8q21.3-q22.1 (MKS3), 12q21.31-q21.33 (MKS4), 16q12.2 (MKS5), and 4p15.3 (MKS6). This mapping suggests genetic heterogeneity in Meckel-Gruber syndrome.
Differential diagnosis
Trisomy 13 may have similar findings as seen in Meckel-Gruber syndrome. Any fetus, however, with a neural tube defect (particularly an encephalocele) can be considered as a possible Meckel-Gruber syndrome, particularly if the kidneys are abnormal.
Prognosis
Lethal - infants born with Meckel-Gruber syndrome are stillborn or die within a few hours to days after birth.
Recurrence risk
25%.
Management
Pregnancy termination before viability.
Treatment
Currently there is no treatment for this syndrome.
Case reports
During the last six months, we observed three cases of the Meckel Gruber syndrome at State Science Center of Obstetrics and Gynecology, Republic of Uzbekistan.
Case 1
A 22-year-old patient (G2P0A1) presented for sonography at 15 weeks. Her previous pregnancy was terminated six month ago due to Meckel-Gruber syndrome of the fetus at 21st week of pregnancy.
Our examination found an encephalocele involving the posterior fossa with a large posterior fossa cyst protruding from the occiput. Cystic hygroma was also found. The kidneys were echogenic, suggesting cystic dysplasia. Based on these findings, recurrent diagnosis of Meckel-Gruber was made. The patient elected to terminate the pregnancy, and the diagnosis was confirmed after delivery.
Image 1: 15 weeks of pregnancy; occipital encephalocele and mild oligohydramnios was present.