International Journal of Biomedical Materials Research
Volume 4, Issue 3, December 2016, Pages: 31-34

 Case Report

Diagnosis of Meckel Gruber Syndrome Ultrasound Scan

Ala Mohammed Abd Elgyoum1, 2, *, Elrashed Abd Elrahim Mohammed1, 3, Ahmed Abdelrahim Mohammed3

1College of Applied Medical Science, Taif University, Taif, Saudi Arabia

2Faculty of Radiological and Nuclear Medicine Science, National Ribat University, Khartoum, Sudan

3Faculty of Radiological Science and Medical Imaging, Alzaiem Alazhari University, Khartoum, Sudan

Email address:

(A. M. A. Elgyoum)

*Corresponding author

To cite this article:

Ala Mohammed Abd Elgyoum, Elrashed Abd Elrahim Mohammed, Ahmed Abdelrahim Mohammed. Diagnosis of Meckel Gruber Syndrome Ultrasound Scan. International Journal of Biomedical Materials Research. Vol. 4, No. 3, 2016, pp. 31-34. doi: 10.11648/j.ijbmr.20160403.14

Received: September 27, 2016; Accepted: October 31, 2016; Published: December 8, 2016


Abstract: Meckel syndrome is a rare lethal ciliopathic genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations, polydactyly, hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios. 34 years old, neither diabetic nor hypertensive, she is gravida III, para I, came for first ultrasound scan with amenorrhea for four months. The ultrasound scan shows single viable fetus, gestational age was 19 weeks + 5 days, with enlarged highly echogenic kidneys.

Keywords: Meckel Syndrome, Central Nervous System Malformations, Polydactyly and Hepatic Developmental Defects


1. Introduction

Meckel syndrome (also known as Meckel–Gruber Syndrome, Gruber Syndrome, Dysencephalia Splanchnocystica) is a rare, lethal, ciliopathic, genetic disorder, characterized by renal cystic dysplasia, central nervous system malformations (occipital encephalocele), polydactyly (post axial), hepatic developmental defects, and pulmonary hypoplasia due to oligohydramnios.

Meckel–Gruber syndrome is named for Johann Meckel and Georg Gruber. [1-3] The first reports of Meckel-Gruber syndrome (MKS) were published in 1822 by Johann Friedrich Meckel. G.B. Gruber also published reports of patients with Meckel-Gruber syndrome in 1934 and gave it the name dysencephalia splanchnocystica. 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), [4-5] 12q21.31-q21.33 (MKS4), [6] 16q12.2 (MKS5), [7] and 4p15.3 (MKS6) [8]. This mapping suggests genetic heterogeneity in Meckel-Gruber syndrome. More than 200 cases have been reported.

The triad of occipital encephalocele, large polycystic kidneys, and postaxial polydactyly characterizes Meckel-Gruber syndrome. Associated abnormalities include oral clefting; genital anomalies; CNS malformations, including Dandy-Walker and Arnold-Chiari malformation; and liver fibrosis. Pulmonary hypoplasia is the leading cause of death. Improvements in ultrasonography have enabled prenatal diagnosis as early as 10 weeks' gestation [8].

2. Case Report

34 years old, neither diabetic nor hypertensive, she is gravida III, para I, came for first ultrasound scan with amenorrhea for four months. The ultrasound scan shows single viable fetus, gestational age was 19 weeks + 5 days, with enlarged highly echogenic kidneys, the head shows posterior cranial defect with protrusion of brain tissues encephalocele. The fingers were not clearly seen because of hydramnios. The conclusion is Meckel Gruber syndrome (FIG 1, 2 and 3).

3. Diagnosis

Dysplastic kidneys are prevalent in over 95% of all identified cases. When this occurs, microscopic cysts develop within the kidney and slowly destroy it, causing it to enlarge to 10 to 20 times its original size. The level of amniotic fluid within the womb may be significantly altered or remain normal, and a normal level of fluid should not be criteria for exclusion of diagnosis.

Occipital encephalocele is present in 60% to 80% of all cases, and post-axial polydactyly is present in 55% to 75% of the total number of identified cases. Bowing or shortening of the limbs are also common.

Finding at least two of the three phenotypic features of the classical triad, in the presence of normal karyotype, makes the diagnosis solid. Regular ultrasounds and pro-active prenatal care can usually detect symptoms early on in a pregnancy.

4. Pathophysiology

Meckel Gruber Syndrome is an autosomal recessive lethal malformation. Recently, two MKS genes, MKS1 and MKS3, have been identified. A study done recently has described the cellular, sub-cellular and functional characterization of the novel proteins, MKS1 and meckelin, encoded by these genes [9]. The malfunction of this protein production is mainly responsible for this lethal disorder. Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely varying, phenotypically-observed disorders. Thus, Meckel–Gruber syndrome is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, Bardet–Biedl syndrome, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, and some forms of retinal degeneration. The MKS1 gene has been explicitly identified as a ciliopathy [10].

5. Incidence

While not precisely known, it is estimated that the general rate of incidence, according to Bergsma, [11] for Meckel syndrome is 0.02 per 10,000 births. According to another study done six years later, the incidence rate could vary from 0.07 to 0.7 per 10,000 births [12]. This syndrome is a Finnish heritage disease. Its frequency is much higher in Finland, where the incidence is as high as 1.1 per 10,000 births. It is estimated that Meckel syndrome accounts for 5% of all neural tube defects there. [13]

6. Radiographic Features

Antenatal ultrasound, in addition to demonstration of the classical features such as an occipitalencephalocoele, multiple renal cysts and polydactyly, there may be evidence of oligohydramnios (or anhydramnios in severe cases) and microcephaly). In utero (and early neonatal life) multicystic renal disease is usually evident as enlarged echogenic kidneys: demonstration of physical cysts within the kidneys only occurs in the minority of cases [14].

7. Differential Diagnosis

The differential diagnosis will depend on the type of the anomalies. Due to several sonographic similarities between these conditions, Trisomy 13 must be excluded by karyotype. Another possible differential diagnosis is autosomal dominant polycystic kidney disease. The constellation of possible anomalies associated with this syndrome is extensive. In some situations, such a wide phenotypic variation makes the recognition of the disease more difficult [15].

8. Discussion

An association of Meckel Gruber syndrome with Rokitansky syndrome and short limb dwarfism has been reported in literature. Other inconstant features include fascial cleft, microcephaly, cerebellar and cerebral hypoplasia, hydrocephalus, sloping forehead, congenital heart disease and pulmonary hypoplasia. Association genital anomalies in males are hypoplastic penis, cryptorchidism, Mullerian duct remnants and epididymal cysts, while septate vagina and hypoplastic or bicornuate uterus may be the associated anomalies in females. However, Meckel Gruber syndrome may demonstrate variation in phenotypic expression when some malformations are different from those traditionally accepted and cases may be evaluated as a different syndrome [16]. We were able to make the diagnosis of Meckel Gruber syndrome at 11 weeks and 6 days. As it is possible to diagnose most cases of Meckel Gruber syndrome at this early gestation, provided that a careful systemic survey is included routinely as part of 11 to 14 weeks scan. It is in fact easier at this stage, as in the presence of oligohydramnios in the second trimester could easily cause encephalocele and polydactyly to be missed. Whereas, early in pregnancy the diagnosis is greatly facilitated by the fact that the amount of amniotic fluid is not affected by the renal anomaly [17].

9. Conclusion

Nuchal translucency measurement and first trimester mini-anomaly scan can prove to be an effective screening tool for Meckel Gruber syndrome ensuring early diagnosis and timely termination of pregnancy.

Fig. 1. TAS showing both kidneys.

Fig. 2. TAS showing fetal femur and an encephalocele.

Fig. 3. TAS showing an encephalocele.


References

  1. Synd, whonamedit, A dictionary of medical eponyms, online in 16/10/2016. http://www.whonamedit.com/synd.cfm/2055.html
  2. J. F. Meckel. Beschreibung zweier durch sehr ähnliche Bildungsabweichungen entstellter Geschwister. Deutsches Archiv für Physiologie, 1822, 7: 99–172.
  3. G. B. Gruber. Beiträge zur Frage "gekoppelter" Missbildungen (Akrocephalossyndactylie und Dysencephalia splancnocystica. Beitr path Anat, 1934, 93: 459–476.
  4. Smith UM, Consugar M, Tee LJ, McKee BM, Maina EN, Whelan S. The transmembrane protein meckelin (MKS3) is mutated in Meckel-Gruber syndrome and the wpk rat. Nat Genet. 2006 Feb. 38(2):191-6.[Medline].
  5. Lu Y, Peng H, Jin Z, Cheng J, Wang S, Ma M, et al.Preimplantation Genetic Diagnosis for a Chinese Family with Autosomal Recessive Meckel-Gruber Syndrome Type 3 (MKS3). PLoS One. 2013 Sep 5. 8(9):e73245. [Medline]. [Full Text].
  6. Baala L, Audollent S, Martinovic J, Ozilou C, Babron MC, Sivanandamoorthy S. Pleiotropic effects of CEP290 (NPHP6) mutations extend to Meckel syndrome. Am J Hum Genet. 2007 Jul. 81(1):170-9.[Medline].
  7. Delous M, Baala L, Salomon R, Laclef C, Vierkotten J, Tory K. The ciliary gene RPGRIP1L is mutated in cerebello-oculo-renal syndrome (Joubert syndrome type B) and Meckel syndrome. Nat Genet. 2007 Jul. 39(7):875-81. [Medline].
  8. Tallila J, Jakkula E, Peltonen L, Salonen R, Kestila M. Identification of CC2D2A as a Meckel syndrome gene adds an important piece to the ciliopathy puzzle. Am J Hum Genet. 2008 Jun. 82(6):1361-7. [Medline].[Full Text].
  9. Dawe, H.R.; Smith, U.M., Cullinane, A.R., Gerrelli, D., Cox, P., Badano, J.L., Blair-Reid, S., Sriram, N., Katsanis, N., Attie-Bitach, T., Afford, S.C., Copp, A.J., Kelly, D.A., Gull, K. and Johnson, C.A. (2007). "The Meckel–Gruber Syndrome proteins MKS1 and meckelin interact and are required for primary cilium formation". Human Molecular Genetics 16 (2): 173–186.doi:10.1093/hmg/ddl459. PMID 17185389.
  10. Badano, Jose L.; Norimasa Mitsuma; Phil L. Beales; Nicholas Katsanis (Sep 2006). "The Ciliopathies : An Emerging Class of Human Genetic Disorders".Annual Review of Genomics and Human Genetics 7: 125–148.doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. Retrieved2008-06-15.
  11. Kyttälä, Mira (May 2006). "Identification of the Meckel Syndrome Gene (MKS1) Exposes a Novel Ciliopathy" (pdf). National Public Health Institute, Helsinki. Retrieved 2008-07-06.
  12. Bergsma, D. (1979). "Birth Defects". Atlas and Compendium. London: Macmillan Press.
  13. Salonen, R.; Norio, R.; Reynolds, James F. (1984). "The Meckel syndrome: Clinicopathological Findings in 67 Patients". American Journal of Medical Genetics18 (4): 671–689. doi:10.1002/ajmg.1320180414. PMID 6486167.
  14. Dr Henry KnipeDr Yuranga Weerakkody et al, Meckel-Gruber syndrome, https://radiopaedia.org/articles/meckel-gruber-syndrome, On line at Wednesday12/10/2016.
  15. Nyberg, D. A. et al.(1990). "Meckel–Gruber syndrome; Importance of PrenatalDiagnosis". Journal of Ultrasound Medicine 9: 691–696.
  16. N Dahiya, S Vijay, S Prabhakar, S Subhramaniam, Neha Dahiya, Antenatal Ultrasound diagnosis of Meckel-Gruber syndrome, 2001 | Volume : 11 | Issue : 4 | Page: 199-201
  17. S. Munim, S. Nadeem, R. Sikandar, First Trimester Diagnosis of Meckel Gruber Syndrome in Pregnancy, Department of Obstetrics and Glynaecology, Aga Khan University Hospital, Karachi, On line in Wednesday12/10/2016.

Article Tools
  Abstract
  PDF(280K)
Follow on us
ADDRESS
Science Publishing Group
548 FASHION AVENUE
NEW YORK, NY 10018
U.S.A.
Tel: (001)347-688-8931