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 Table of Contents 
CASE REPORT
Year : 2013  |  Volume : 2  |  Issue : 1  |  Page : 106-108  

Meckel gruber syndrome: Report of two cases with review of literature


Department of Pathology, SDM College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka, India

Date of Web Publication3-Apr-2013

Correspondence Address:
Aneel Myageri
Department of Pathology, SDM College of Medical Sciences and Hospital, Sattur, Dharwad, Karnataka
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4863.109971

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  Abstract 

Meckel Gruber syndrome (MKS) is a lethal, autosomal, recessive, multisystemic disorder, associated with mutations affecting ciliogenesis. Since the time it was first reported; only 200 cases have been reported. From January 2004 to December 2010, we evaluated 268 fetal autopsies in our institute, in the Department of Pathology; two of these fetuses were diagnosed as MKS. MKS is characterized by occipital meningoencephalocele, cystic kidneys, postaxial polydactyly, and fibrosis in the liver. MKS cases show genetic heterogeneity. MKS results in 100% fetal or neonatal mortality. As MKS has a high risk (25%) of recurrence; parents should be counseled for future pregnancies.

Keywords: Autopsy, fetal mortality, Meckel Gruber syndrome


How to cite this article:
Myageri A, Grampurohit V, Rao R. Meckel gruber syndrome: Report of two cases with review of literature. J Family Med Prim Care 2013;2:106-8

How to cite this URL:
Myageri A, Grampurohit V, Rao R. Meckel gruber syndrome: Report of two cases with review of literature. J Family Med Prim Care [serial online] 2013 [cited 2019 Aug 25];2:106-8. Available from: http://www.jfmpc.com/text.asp?2013/2/1/106/109971


  Introduction Top


Meckel Gruber syndrome (MKS) is a lethal, autosomal, recessive, multisystemic disorder, associated with mutations affecting ciliogenesis. [1] In 1822, Johann Friedrick Meckel described two siblings who presented with occipital meningoencephalocele, polydactyly, cleft palate, and large cystic kidneys. George B Gruber, in 1934, reported 16 similar cases and named the disorder, 'Dysencephalia Splanchnocystica'. In 1969, Opitz and Howe re-described it as the MKS. [2] Since the time it was first reported; only 200 cases have been reported. [3] From January 2004 to December 2010 we evaluated 268 fetal autopsies in our institute in the Department of Pathology; two of these fetuses were diagnosed as MKS.


  Case History Top


In the first case, a 26-year-old patient, with 17 weeks of gestation, decided to terminate the pregnancy after ultrasonography (USG) revealed a single fetus with microcephaly and occipital meningoencephalocele [Figure 1]a and b. There was second-degree consanguinity. She was not on teratogenic drugs. The female fetus weighing 95 g was sent for autopsy. On examination the fetus showed occipital meningoencephalocele [Figure 2]a, along with low set ears, microcephaly, absence of forehead, hypertelorism, large protruding eyes, a large nose, and a short neck. There was postaxial polydactyly [Figure 3]a.
Figure 1: (a) USG of case 1 showing microcephaly, (b) USG of case 1 showing occipital encephalocele

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Figure 2: (a) Occipital encephalocele in case 1. (b) Occipital encephalocele in case 2

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Figure 3: (a) Postaxial polydactyly in case 1. (b) Bilateral renal cystic dysplasia of kidney in case 2

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The second case was of a 35-year-old female patient, with 20 weeks of gestation. Ultrasonographic examination revealed a single intrauterine pregnancy, with meningoencephalocele and polycystic kidneys with reduced liquor. There was no history of consanguinity or teratogenic drugs. The pregnancy was terminated and a female fetus delivered, weighing 540 g, which was sent for autopsy. On examination, the fetus showed occipital meningoencephalocele [Figure 2]b measuring 3 × 2.5 × 2 cm. The bilateral kidneys were large lobulated and cystic [Figure 3]b. Both lungs were hypoplastic. Microscopically, the kidneys showed features of cystic renal dysplasia and the liver showed periportal fibrosis [Figure 4]a and b.
Figure 4: (a) Renal cystic dysplasia in case 2. (b) Periportal fibrosis in liver of case 2

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In both cases, the diagnosis of MKS was confirmed after autopsy. In both cases the parents did not give consent for molecular analysis, but were re-counseled for future pregnancies.


  Discussion Top


MKS is characterized by occipital meningoencephalocele, cystic kidneys, postaxial polydactyly, and fibrosis in liver. The worldwide incidence of MKS varies from 1/140,000 (Great Britain) to 1/3500 (North Africa) in live births. [4] A higher incidence is recorded in Gujarati Indians, Belgians, Bedonins. [2],[5] The male-to-female ratio is equal. MKS shows genetic heterogeneity. Six genetic loci were identified for MKS. They are MKS1, on 17q21-24, in Finnish and Caucasian people; MKS2, on 11q13, in the Middle East and North African families and MKS3, on 8q24, in Pakistan and Northern India. [4],[6]

MKS1 is a centrosomal protein required for ciliogenesis, and mutation in MKS1 results in defects in ciliogenesis that underlie a majority of phenotypes shown by patients. [1]

Two of the three major anomalies or two other anomalies in addition to the one classical finding are sufficient for a definitive diagnosis. [4],[6],[7],[8] In our first case occipital meningoencephalocele with polydactyly and other associated anomalies were present, but the kidneys were normal. In the second case there were occipital meningoencephalocele, bilateral polycystic kidneys, and fibrotic changes in the liver, but polydactyly was absent. Although postaxial polydactyly is a feature described in MKS, it is seen only in 80% of the cases. [4]

Other anomalies of MKS include CNS malformations like microcephaly, anencephaly, holoprosencephaly, hydrocephalus, polymicrogyria, Arnold-Chiari or Dandy-Walker malformation, agenesis of corpus callosum, absence of olfactory tract or lobe; and cardiac anomalies like atrial septal defect (ASD), ventricular septal defect (VSD), or a patent ductus artery (PDA). Cleft palate, microphthalmia, sloping forehead, micrognathia, short neck, and cryptorchidism are also noted. [7],[9]

The differential diagnosis of MKS includes Bardet-Biedl syndrome (BBS), Trisomy 13, and Smith-Lemli-Opitz syndrome. CNS anomalies are not seen in BBS, whereas, karyotype analysis will be abnormal in Trisomy 13. In MKS cases the karyotype is normal. In the Smith-Lemli-Opitz syndrome, due to mutations and deficiency of 7-dehydrocholesterol gama-reductase, hepatic dysfunction and cholestatic liver disease are seen. [4],[10]

The MKS can be diagnosed by USG done at 11 to 14 weeks of gestational age and by estimation of alpha fetoprotein in the maternal serum. Sometimes, the alpha fetoprotein level is not elevated when the encephalocele contains a closed sac. When available, autopsy and genetic analysis are gold standard for diagnosis. [6]

The MKS results in 100% fetal or neonatal mortality. As MKS has a high risk (25%) of recurrence; parents should be counseled for future pregnancies. [4],[9]

Birth defects often pose a diagnostic and management challenge. So, preventive measures should start at the primary health care (PHC) level. PHC providers should give preconception care, to ensure the optimal physical and mental well-being of women, to increase the likelihood of a normal pregnancy. The timely identification of a family risk of birth defects is necessary. Such services include prenatal screening and diagnosis for birth defects, selective termination of pregnancy, and the availability of counseling services. Care and support should always be given by the primary health care provider, with assistance from the medical genetic specialist or other specialists, when needed.


  Conclusion Top


The MKS has a high recurrence risk. PHC providers should use a methodical approach for birth defects, to allow accurate diagnostic and recurrence risk counseling, informed management decisions, and the apt provision of medical resources. Although improved prenatal testing has increased the detection of fetal abnormalities, an autopsy remains valuable, as it provides morphological confirmation.

 
  References Top

1.Cui C, Chatterjee B, Francis D, Yu Q, SanAgustin JT, Francis R, et al. Disruption of Mks1 localization to the mother centriole causes cilia defects and developmental malformations in Meckel-Gruber syndrome. Dis Model Mech 2011;4:43-56.  Back to cited text no. 1
    
2.Salonen R, Paavola P. Meckel syndrome. J Med Genet 1998;35:497-501.  Back to cited text no. 2
    
3.Jones KL. Meckel-Gruber syndrome. In: Jones KL, editor. Smith's recognizable patterns of human malformation. 6 th ed. Philadelphia: Elsevier saunders; 2006. p.198-9.  Back to cited text no. 3
    
4.Hakverdi S, Güzelmansur I, Sayar H, Arif G, Hakverdi AU, Toprakl S. Meckel-Gruber syndrome: A report of three cases. Perinat J 2010;18:59-63.  Back to cited text no. 4
    
5.Young ID, Rickett AB, Clarke M. High incidence of Meckel's syndrome in Gujarati Indians. J Med Genet 1985;22:301-4.  Back to cited text no. 5
    
6.Panduranga C, Kangle R, Badami R, Patil PV. Meckel-Gruber syndrome: Report of two cases. J Neurosci Rural Pract 2012;3:56-9.  Back to cited text no. 6
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7.Balcý S, Teksen F, Dökmeci F, Cengiz B, Cömert RB, Can B, et al. Prenatal diagnosis of Meckel-Gruber syndrome and Dandy-Walker malformation in four consecutive affected siblings, with the fourth one being diagnosed prenatally at 22 weeks of gestation. Turk J Pediatr 2004;46:283-8.  Back to cited text no. 7
    
8.Roume J, Ma HW, Le Merrer M, Cormier-Daire V, Girlich D, Genin E, et al. Genetic heterogeneity of Meckel syndrome. J Med Genet 1997;34:1003-6.  Back to cited text no. 8
    
9.Ramchandran U, Malla T, Joshi KS. Meckel-Gruber syndrome. Kathmandu Univ Med J (KUMJ) 2006;4:334-6.  Back to cited text no. 9
    
10.Chen CP. Meckel syndrome: Genetics, perinatal findings and differential diagnosis. Taiwan J Obstet Gynecol 2007;46:9-14.  Back to cited text no. 10
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]


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