Meckel Gruber and Joubert Syndrome Diagnosed Prenatally: Allelism between the Two Ciliopathies, Complexities of Mutation Types and Digenic Inheritance

Abstract

Background: Antenatally detected occipital encephalocele and polycystic kidneys are a common presentation of ciliopathies like Joubert syndrome and Meckel Gruber syndrome which have considerable genetic and phenotypic overlap. Case reports: We describe 3 cases of antenatally diagnosed occipital encephalocele and enlarged kidneys with fetal autopsy, histopathology & exome sequencing results. A novel nonsense variant in the CEP290 gene was reported in first case (Meckel syndrome). The second case shows the importance of fetal exome where the parents were carriers for 2 ciliopathy genes (TMEM138 & SDCCAG8). Diagnosis in this case was confirmed by fetal exome sequencing (Joubert syndrome). Multiexon deletion in TMEM67 and KIF14 present in trans was identified in the third case (Meckel syndrome), likely resulting in digenic inheritance. Conclusion: We report 2 cases of Meckel syndrome with a novel variant and multiexon deletion, and 1 case of Joubert syndrome which depicts the limitations of preconceptional carrier screening in ciliopathies due to overlapping phenotypes.

Keywords:

• Ciliopathies
• allelism
• Joubert syndrome
• Meckel gruber syndrome
• multiexon deletion

Acknowledgments

We acknowledge the contribution of Medgenome labs who had helped in molecular diagnostics in concessional rate in one family.

Author contribution

Somya Srivastava, Rani Manisha, Aradhana Dwivedi, Harshita Agarwal, Deepti Saxena, Vinita Agrawal, Kausik Mandal were involved in conception, study design, execution, acquisition of data, analysis and interpretation of the study.

Somya Srivastava, Deepti Saxena, Vinita Agrawal and Kausik Mandal drafted, substantially revised and critically reviewed the article.

Declaration of interest

There is no conflict of interest.

Institutional Ethics committee (Name of Institute: Sanjay Gandhi post Graduate Institute of Medical Sciences, Lucknow).

IEC code: 2019-184-IP-EXP-12; Dated 21 Feb, 20.

Funding details

No funding.