Dual independent genetic etiologies in a lethal complex malformation phenotype

Introduction

The etiologic diagnosis of fetal anomaly syndromes remains difficult despite significant advances in prenatal ultrasound, fetal MRI and molecular genetic technologies. We present the challenges of a late prenatal presentation and adverse outcome in a child with multiple malformations, for which joint multidisciplinary efforts have led to a final dual diagnosis of autosomal recessive Boissel syndrome and geleophysic dysplasia.

Publication History

Article published online:
07 April 2020

• References

• 1 Rohena L. et al. FTO variant associated with malformation syndrome. Am J Med Genet A 2016; 170A: 1023-1028
• 2 Boissel S. et al. Loss-of-function mutation in the dioxygenase-encoding FTO gene causes severe growth retardation and multiple malformations. Am J Hum Genet 2009; 85: 106-111
• 3 Allali S. et al. Molecular screening of ADAMTSL2 gene in 33 patients reveals the genetic heterogeneity of geleophysic dysplasia. J Med Genet 2011; 48: 417-421
• 4 Filges I, Friedman JM. Exome sequencing for gene discovery in lethal fetal disorders – harnessing the value of extreme phenotypes. Prenat Diagn 2015; 35: 1005-1009
• 5 Lord J. et al. Prenatal exome sequencing analysis in fetal structural anomalies detected by ultrasonography (PAGE): a cohort study. Lancet 2019; 393: 747-757
• 6 Petrovski S. et al. Whole-exome sequencing in the evaluation of fetal structural anomalies: a prospective cohort study. Lancet 2019; 393: 758-767
• 7 Ferretti L, Mellis R, Chitty LS. Update on the use of exome sequencing in the diagnosis of fetal abnormalities. Eur J Med Genet 2019; 62: 103663
• 8 Monaghan KG. et al ACMG Professional Practice and Guidelines Committee. The use of fetal exome sequencing in prenatal diagnosis: a points to consider document of the American College of Medical Genetics and Genomics (ACMG). Genet Med 2020; [Epub ahead of print]