Case of the Week #553

Oueslati Boujemaa (1); Cerine Jeanty (2)
(1) Belveder Centre: Centre de Médecine et d’Echographie Materno-Fœtales, Tunis, TUNISIE; (2) St Mary's Medical Center, San Francisco, California, United States

Posting Dates: February 15 - February 28, 2022

Case Report: 28-year-old G5P0 woman in a consanguineous relationship was referred to our center at 12 weeks, 5 days of gestation for ultrasound evaluation due to history of prior fetal anomalies. The patient previously had 4 fetal losses, two terminations and two pregnancies affected with fetal anomalies.

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We present a case of  Meckel Gruber Syndrome.

Ultrasound findings in the first trimester demonstrate elevated nuchal translucency, an anomaly of the posterior fossa, occipital encephalocele, polycystic kidneys and polydactyly (unilateral hexadactyly in one hand and polydactyly of the foot) consistent with Meckel Gruber Syndrome. The patient requested a termination of pregnancy. Pathologic exam and karyotype of the current case was not performed.

The patient had a history of two prior pregnancies with fetal hydrocephalus. The pathology of the previous case was obtained and revealed a male fetus of approximately 26 weeks gestation with microcephaly, encephalocele, polycystic kidneys, hexadactyly, liver fibrosis, and pulmonary hypoplasia. The heart was normal.


Meckel-Gruber syndrome is a lethal autosomal recessive disease characterized by a triad of brain malformation, polycystic kidneys, and polydactyly [1]. It was first described by Johann Friedrich Meckel in 1822 [2]. It occurs in approximately 1 in 135,000 live births in Europe [3], but may be more frequent in certain populations in Finland (1in 9,000) [4], Kuwaiti Bedouin populations (1in 3,500) [5], and Gujarati Indians (1 in 1,300) [6]. It is caused by mutations in cilia-related genes and often occurs in the context of consanguineous unions. Mutations in 14 genes encoding proteins that are structural or functional components of the primary cilium have been identified to cause Meckel-Gruber syndrome. Several other genes have been implicated on the basis of pathogenic private mutations in individual families with either Meckel-Gruber syndrome or Meckel-Gruber-like phenotypes [7]. In total, these genes explain only 50-60% of Meck Gruber cases [7].

The primary cilium is a microtubule-based organelle that projects from the apical surface of vertebrate cells. It acts as an “antenna,” receiving and transducing chemosensory and mechanosensory signals that regulate pathways such as Wnt and Shh which have essential roles during embryonic development [7].

Clinical manifestations include central nervous system anomalies such as occipital encephalocele, hydrocephalus, anencephaly, holoprosencephaly, as well as Dandy-Walker [8,9]. Polydactyly may affect all four extremities and is typically postaxial (80%) [7,9]. Other anomalies may include cleft lip/palate, cardiac and genital anomalies, liver fibrosis, and bone dysplasia [8,9]. Affected individuals have oligohydramnios due to renal dysfunction resulting in pulmonary hypoplasia [7].

The diagnosis can be made on prenatal ultrasonography and is often detected before the 14th gestational week [10]. The fetal bladder can also be visualized by ultrasonography from 11 weeks, and the absence of a visible fetal bladder is often indicative of renal dysfunction [7]. Molecular genetic testing can be used to confirm the diagnosis or to guide genetic counseling. At-risk couples, in which both individuals are carriers of a disease-causing mutation, have a 25% risk of having an affected child with each pregnancy [7].

Differential diagnoses include trisomy 13, Bardet-Biedl syndrome, Hydrolethalus, and Smith-Lemli-Opitz Syndrome [1, 7].


[1] Attie-Bitach, T. “Meckel syndrome.” Orphanet., Last update 2/2021.
[2] Meckel J. Beschreibung zweier, durch sehr ähnliche Bildungsabweichungen  entstellter Geschwister. Dtsch Arch Physiol (1882) 7:99–172.
[3] Auber B, Burfeind P, Herold S, et al. A disease causing deletion of 29 base pairs in intron 15 in the MKS1 gene is highly associated with the campomelic variant of the Meckel-Gruber syndrome. Clin Genet (2007) 72:454–9.
[4] Salonen R, Norio R. The Meckel syndrome in Finland: epidemiologic and genetic aspects. Am J Med Genet (1984) 18:691–8.
[5] Teebi AS, Alsaleh QA, Odeh H. Meckel syndrome and neural-tube defects in Kuwait. J Med Genet (1992) 29:140.
[6] Young ID, Rickett AB, Clarke M. High-incidence of Meckels syndrome in Gujarati Indians. J Med Genet (1985) 22:301–4.
[7] Hartill V, Szymanska K, Sharif S et al. Meckel-Gruber Syndrome: An Update on Diagnosis, Clinical Management, and Research Advances. Front Pediatr. 2017 Nov 20;5:244.
[8] Fraser FC, Lytwyn A. Spectrum of anomalies in the Meckel syndrome,  or maybe there is a malformation syndrome with at least one constant anomaly. Am J Med Genet (1981) 9:67–73.
[9] Salonen R. The Meckel syndrome – clinicopathological findings in 67 patients. Am J Med Genet (1984) 18:671–89.
[10] Sepulveda W, Sebire NJ, Souka A, et al. Diagnosis of the Meckel-Gruber syndrome at eleven to fourteen weeks’ gestation. Am J Obstet Gynecol (1997) 176:316–9.

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