Infant mortality: the contribution of genetic disorders

Abstract

Objective: To determine the proportion of infant deaths occurring in the setting of a confirmed genetic disorder.

Study design: A retrospective analysis of the electronic medical records of infants born from 1 January, 2011 to 1 June, 2017, who died prior to 1 year of age.

Results: Five hundred and seventy three deceased infants were identified. One hundred and seventeen were confirmed to have a molecular or cytogenetic diagnosis in a clinical diagnostic laboratory and an additional seven were diagnosed by research testing for a total of 124/573 (22%) diagnosed infants. A total of 67/124 (54%) had chromosomal disorders and 58/124 (47%) had single gene disorders (one infant had both). The proportion of diagnoses made by sequencing technologies, such as exome sequencing, increased over the years.

Conclusions: The prevalence of confirmed genetic disorders within our cohort of infant deaths is higher than that previously reported. Increased efforts are needed to further understand the mortality burden of genetic disorders in infancy.

Figure 1.. Cohort overview.

“Known or suspected disorder” includes infants who had either a prenatal diagnosis made, a clinical genetics consultation, or a molecular or cytogenetic test sent (testing sent at our hospital or elsewhere).

Figure 2.. Testing modality leading to diagnosis.

Of the 25 “unknown” modalities, 18 were chromosomal aneuploidy syndromes, three were diagnoses of chromosome 22q11 deletion syndrome, two were single gene disorders, one was a tumor variant confirmed in a germline tissue, and one was a chromosomal translocation. Three of the deletion/duplication diagnoses were chromosomal, and the remainder represented deletions in single genes. FISH, fluorescence in situ hybridization.

Figure 3.. Diagnoses by testing modality and year.

This includes only postnatal diagnoses made by a clinical laboratory. For infants for whom the exact date of diagnosis was unknown, the date of birth was used.