PP-17 A case of Meckel-Gruber syndrome diagnosed in the first trimester

Objective

Meckel-Gruber syndrome (MGS), an autosomal recessively inherited hereditary syndrome from the group of ciliopathies, is characterized by occipital encephalocele, large polycystic kidneys and postaxial polydactyly, resulting from the involvement of multiple genes and therefore has 15 phenotypes, occurring in 1 in 13,250-140,000 live births worldwide. Prenatal ultrasonography is the best available method to diagnose MGS. In this report, we aimed to present the prenatal diagnosis of a first trimester MGS case.
 

Case

A 25-year-old patient with gravida 3, parity 1, 14 weeks and 1 day gestation according to the last menstrual period was admitted to the prenatal diagnosis and treatment unit of our clinic for a first trimester screening test. In the ultrasonographic examination of the patient who had a history of MGS in her previous pregnancy, fetal cranial evaluation revealed acrania, exencephaly, anencephaly sequence (figure 1) and open spina bifida anomaly. Fetal abdominal evaluation revealed bilateral cystic kidneys (figure 2). Fetal extremity evaluation revealed no clear evaluation for postaxial polydactyly. The family was informed in detail about the possible poor fetal/neonatal prognosis of the fetus, which was primarily diagnosed as MGS according to the sonographic findings, and invasive prenatal diagnostic testing and pregnancy termination were presented as options. The family decided to terminate the pregnancy without invasive prenatal diagnostic testing. After termination of pregnancy, genetic examination of the abortion material was requested. Macroscopic examination of the abortion material confirmed prenatal findings (figure 3). The family was referred to the genetics outpatient clinic.
 

Discussion

Prenatal features of MKS, such as postaxial polydactyly, encephalocele, and polycystic kidneys, are often profound and easily detectable in the first trimester. The findings of a large population-based review that estimated the incidence of typical symptoms were as follows: encephalocele, 83.8%; polydactyly, 87.3%; and cystic kidney disease, 97.7%.[2] Therefore, targeted prenatal diagnosis of MKS is usually triggered by these findings. However, the presence of encephalocele is not specific to MKS. Only 21% of fetuses diagnosed with prenatal encephalocele will have MCS,[3] and the same is true for polycystic kidney finding. The majority of confirmed hereditary cystic kidney disease detected prenatally is autosomal recessive polycystic kidney disease (ARPKD), diagnosed in 81% of cases. Meckel-Gruber syndrome was found in only 8% of such cases.[5]
 

Conclusion

MGS is a rare autosomal recessive condition with a mortality of 100%; diagnosis is possible antenatally even in the first trimester of pregnancy by prenatal sonographic examination. Given its mortality, early diagnosis of MGS and other such lethal anomalies has a significant impact on family counseling, especially when it comes to termination of pregnancy. Early prenatal diagnosis and genetic counseling are important in the management of this case with a first trimester prenatal diagnosis due to the high recurrence rate of 25% in subsequent pregnancies of the mother.

Keywords

Ensephalocele, fetal kidney, meckel gruber syndrome, polydactyly

1. Chen CP. Meckel syndrome: genetics, perinatal findings, and differential diagnosis. Taiwan J Obstet Gynecol. 2007 Mar;46(1):9-14.  
2. Barisic, I., Boban, L., Loane, M., Garne, E., Wellesley, D., Calzolari, E., … Verellen-Dumoulin, C.(2015). Meckel–Gruber Syndrome: A population-based study on prevalence, prenatal diagnosis, clinical features, and survival in Europe. European Journal of Human Genetics,  23,  746–752. 
3. Weichert, J., Hoellen, F., Krapp, M., Germer, U., Axt-Fliedner, R., Kempe, A., … Gembruch, U. (2017). Fetal cephaloceles: Prenatal diagnosis and course of pregnancy in 65 consecutive cases. Archives of Gynecology and Obstetrics,  296,  455–463.
4. Hartill V, Szymanska K, Sharif SM, Wheway G, Johnson CA. Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances. Front Pediatr. 2017 Nov 20;5:244.
5. Erger, F., Bruchle, N. O., Gembruch, U., & Zerres, K. (2017). Prenatal ultrasound, genotype, and outcome in a large cohort of prenatally affected patients with autosomal-recessive polycystic kidney disease and other hereditary cystic kidney diseases. Archives of Gynecology and Obstetrics, 295,  897–906.

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