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

Gregory Costain; Michal Inbar-Feigenberg; Maha Saleh; Shimrit Yaniv-Salem; Greg Ryan; Eric Morgen; Elaine S. Goh; Gen Nishimura; David Chitayat

doi:10.1055/s-0038-1636995

Journal of Pediatric Genetics, Table of Contents

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^*

¹Medical Genetics Residency Training Program, University of Toronto, Toronto, Ontario, Canada

²Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

,

Michal Inbar-Feigenberg^*

²Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

,

Maha Saleh

¹Medical Genetics Residency Training Program, University of Toronto, Toronto, Ontario, Canada

²Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

,

Shimrit Yaniv-Salem

³Fetal Medicine Unit, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

,

Greg Ryan

³Fetal Medicine Unit, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

,

Eric Morgen

⁴Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

,

Elaine S. Goh

⁵Department of Laboratory Medicine and Genetics, Trillium Health Partners, Mississauga, Ontario, Canada

,

Gen Nishimura

⁶Intractable Disease Center, Saitama Medical University Hospital, Saitama, Japan

,

David Chitayat

²Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

⁷The Prenatal Diagnosis and Medical Genetics Program, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada

› Author Affiliations

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.

Keywords

lysosomal storage disease - mucolipidosis - prenatal diagnosis - genetic testing - skeletal dysplasia

Full Text

References

References
1 Best S, Wou K, Vora N, Van der Veyver IB, Wapner R, Chitty LS. Promises, pitfalls and practicalities of prenatal whole exome sequencing. Prenat Diagn 2018; 38 (01) 10-19
2 Leroy JG, Cathey S, Friez MJ, Mucolipidosis II. 2008 Aug 26 [Updated 2012 May 10]. In: Adam MP, Ardinger HH, Pagon RA. , et al., eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2018. Available at: https://www.ncbi.nlm.nih.gov/books/NBK1828/
3 Plante M, Claveau S, Lepage P. , et al. Mucolipidosis II: a single causal mutation in the N-acetylglucosamine-1-phosphotransferase gene (GNPTAB) in a French Canadian founder population. Clin Genet 2008; 73 (03) 236-244
4 Kudo M, Brem MS, Canfield WM. Mucolipidosis II (I-cell disease) and mucolipidosis IIIA (classical pseudo-hurler polydystrophy) are caused by mutations in the GlcNAc-phosphotransferase alpha / beta -subunits precursor gene. Am J Hum Genet 2006; 78 (03) 451-463
5 Lai LM, Lachman RS. Early characteristic radiographic changes in mucolipidosis II. Pediatr Radiol 2016; 46 (12) 1713-1720
6 Unger S, Paul DA, Nino MC. , et al. Mucolipidosis II presenting as severe neonatal hyperparathyroidism. Eur J Pediatr 2005; 164 (04) 236-243
7 Lees C, Homfray T, Nicolaides KH. Prenatal ultrasound diagnosis of Leroy I cell disease. Ultrasound Obstet Gynecol 2001; 18 (03) 275-276
8 Rapola J, Aula P. Morphology of the placenta in fetal I-cell disease. Clin Genet 1977; 11 (02) 107-113
9 Saul RA, Proud V, Taylor HA, Leroy JG, Spranger J. Prenatal mucolipidosis type II (I-cell disease) can present as Pacman dysplasia. Am J Med Genet A 2005; 135 (03) 328-332
10 Yuksel A, Kayserili H, Gungor F. Short femurs detected at 25 and 31 weeks of gestation diagnosed as Leroy I-cell disease in the postnatal period: a report of two cases. Fetal Diagn Ther 2007; 22 (03) 198-202
11 Hadlock FP, Harrist RB, Carpenter RJ. , et al. Sonographic estimation of fetal weight. The value of femur length in addition to head and abdomen measurements. Radiology 1984; 150 (02) 535-540
12 Barkova E, Mohan U, Chitayat D. , et al. Fetal skeletal dysplasias in a tertiary care center: radiology, pathology, and molecular analysis of 112 cases. Clin Genet 2015; 87 (04) 330-337
13 Fowler DJ, Anderson G, Vellodi A, Malone M, Sebire NJ. Electron microscopy of chorionic villus samples for prenatal diagnosis of lysosomal storage disorders. Ultrastruct Pathol 2007; 31 (01) 15-21

Supplementary Material

Supplementary Figures