J Pediatr Genet 2018; 07(03): 134-137
DOI: 10.1055/s-0038-1636995
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Challenges in Diagnosing Rare Genetic Causes of Common In Utero Presentations: Report of Two Patients with Mucolipidosis Type II (I-Cell Disease)

Gregory Costain*
1  Medical Genetics Residency Training Program, University of Toronto, Toronto, Ontario, Canada
2  Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
,
Michal Inbar-Feigenberg*
2  Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
,
Maha Saleh
1  Medical Genetics Residency Training Program, University of Toronto, Toronto, Ontario, Canada
2  Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
,
Shimrit Yaniv-Salem
3  Fetal Medicine Unit, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
,
Greg Ryan
3  Fetal Medicine Unit, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
,
Eric Morgen
4  Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
,
Elaine S. Goh
5  Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, Ontario, Canada
,
Gen Nishimura
6  Intractable Disease Center, Saitama Medical University Hospital, Saitama, Japan
,
David Chitayat
2  Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
7  The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
› Author Affiliations
Further Information

Publication History

09 January 2018

05 February 2018

Publication Date:
09 March 2018 (eFirst)

Abstract

Traditional approaches to prenatal genetic diagnosis for common presentations such as short femurs or intrauterine growth restriction are imperfect, and whole-exome sequencing is an emerging option. Mucolipidosis type II (I-cell disease) is an ultra-rare autosomal recessive lysosomal storage disorder with the potential for prenatal-onset skeletal and placental manifestations. We describe the prenatal signs in two recent unrelated patients with confirmed diagnoses soon after birth. In both cases, parents were consanguineous but there was no known family history of mucolipidosis type II. False reassurance was provided after negative testing for another disease with overlapping prenatal manifestations already present in one of the families, emphasizing that offspring of consanguineous parents can be at risk for more than one recessive condition. Our experience illustrates the potential advantages in expanding prenatal applications of WES for the identification of rare single gene disorders in offspring of consanguineous unions.

Ethics Statement

Both families provided informed consent for inclusion in this report. Approval from a Research Ethics Board is not required at our institution for publication of a case series.


* These authors contributed equally.


Supplementary Material