Case Report

Meckel-Gruber Syndrome

^1,Shailaja Shukla¹Mona Bargotya ¹Deepti Verma ¹Sarika Singh²Manisha Kumar*

• ¹Departments of Pathology  and
• ²Obstetrics & Gynecology Lady Hardinge Medical College, New Delhi.

• Submitted: Friday, January 10, 2014
• Accepted: Saturday, April 26, 2014
• Published:  Tuesday, April 29, 2014

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited

Abstract

Meckel Gruber Syndrome (MKS) is a rare autosomal recessive malformation syndrome characterized by multiple congenital anomalies ultimately leading to the death of fetus in utero or shortly after birth. It is characterized by classical triad of occipital encephalocele, infantile polycystic kidneys and postaxial polydactyly. Diagnosis of MKS is made on the basis of ultrasonographic, clinical and morphological findings. Herein we describe two cases of MKS presenting as classical triad.

Key words

Meckel Gruber Syndrome, Fetal anomaly, prenatal diagnosis

Introduction

Meckel Gruber Syndrome (MKS) is a rare autosomal recessive malformation syndrome with a neural tube defect leading to death of the fetus in utero or shortly after birth.First reports of MKS were published in 1822 by Johann Friedrich Meckel [1]. G.B.Gruber also published reports of pateints with MKS in 1934 and gave it the name dysencephalia splanchnocystica [2]. MKS is characterized by triad of large polycystic kidneys(100%),occipital encephalocele(90%),and ostaxial polydactyly(83.3%) [3]. Associated abnormalities include oral clefting, genital anomalies, CNS malformations and liver fibrosis.Mortality rate is 100% with most fetuses surviving only few days to weeks. Pulmonary hypoplasia is the leading cause of death. Worldwide incidence is 1/13,250-140,000 live births.There is a predilection for Belgian 1/3000) and Finish (1/9000) populations [4]. In India, highest incidence is in Gujrati Indians (1 affected birth per 1,300) [5].

Figure 1: Case I showing encephalocele (à) and polydactyly (*)

Figure 2: Case II showing encephalocele («), ambiguous genitilia(*) and polydactyly (à)

Case Presentation

The two cases discussed here were fetuses with abnormal prenatal findings detected during routine ultrasonographic examination. The salient features of both cases are summarized in [Table 1] (Figure 1 and 2).

TABLE 1: Clinical details of the cases

	Age of mother/ gestational age	Consanguinity	Sex of fetus	MKS diagnosed at	Outcome of pregnancy	Clinical findings
Case     I    (Fig 1 )	20 yrs/16 wks	1st degree	male	11 wks	Dilatation and Currettage	16 wks, encephalocele,polydactyly bilateral cystic kidneys, oligohydramnios
Case     II (Fig 2)	24 yrs/36 wks	1st degree	male	36 wks	Still born breech delivery	36 wks, encephalocele,polydactyly bilateral cystic kidneys,ambiguous genitilia,oligohydramnios

Histopathological Findings

Grossly, kidneys in both the cases were enlarged showing multiple cysts and loss of corticomedullary differentiation. Liver showed two cysts measuring 0.2 and 0.8 cm in diameter in case II and autolytic changes in case I (Figure 3) and (Figure 4). However, no cysts in liver were identified in Case I. microscopically, sections from kidneys showed multiple thin walled cysts throughout the parenchyma lined by low cuboidal epithelium and separated by loose connective tissue. Very few glomeruli were seen compressed at the periphery (Figure 5). Sections from liver showed features of ductal plate malformation:proliferation and dilatation of the bile ducts arranged in a ring like manner in few portal tracts with increase of collagenous connective tissue i.e.portal fibrosis (Figure 6). Extramedullary hematopoeisis was also noted.Macroscopic cysts in Case II were lined by columnar épithélium.

Figure 3: Bilateral enlarged kidneys showing multiple cysts and liver showing autolytic changes in Case I

Figure 4: Gross specimen (A):Bilateral enlarged kidneys showing multiple cysts(à) in Case II, (B): Liver showing cysts (à) in case II

Figure 5: Photomicrograph showing (A) Multiple renal cysts lined by low low cuboidal epithelium in case I (H&E x100) (B): Multiple renal cysts with  few glomeuli (à) in case II (H&Ex100)

Figure 6: Photomicrograph showing (A): Ductal plate malformation of liver in case I with partial autolytic changes (H&Ex100)  (B): Liver showing  proliferation of bile ducts in a ring like manner in case II  (H&Ex400)  (C):Liver cyst lined by columnar epithelium(à) in Case II(H&E x100).

Discussion

Significant advances have been made in the clinical diagnosis, understanding the pathogenesis and management of MKS. Multiple genetic mutations have been mapped to 6 different loci in chromosomes17q21-24(MKS1),11q13(MKS2),8q21.3q22.1(MKS3)[6],12q21.31q21.33(MKS4)[7],16q12.2(MKS5)[8] & 4p15.3(MKS6) [9].

In the present cases, there was no history of similar fetal anomalies in the siblings as the mother of case I was a primigravida and case II had a live and healthy two year old sibling. No genetic studies could be done as the facility is not available in our institute.

It is important to thoroughly examine any pregnant female with past history of fetal anomalies in previous pregnancies as there is high risk of recurrence (25%). Early (11-14th week) prenatal ultrasonography is the best method to diagnose MKS [10,11]. Subsequent autopsy and chromosomal or molecular studies are confirmatory.

Key message

MKS is a lethal disorder with 100% mortality. An affected infant even if born alive dies shortly thereafter. Termination of pregnancy at risk of MKS can be offered if detected early by prenatal ultrasonography

Authors' Contribution

SS: Pathological diagnosis and edited final manuscript.

 MB: Literature search and drafted manuscript.

 DV: Literature search and helped in interpretation.

 SS: Helped in drafting manuscript.

MK: Treated the patients and provided clinical details.

Conflict of Interests

The authors declare that there is no conflict of interests

Ethical Considerations

Written informed consent was obtained from the mother of the patient for publication of this case report.

Funding

None declared

Acknowledgement

None declared

References

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