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Meta-Analysis
. 2018 Jun;178(2):187-193.
doi: 10.1002/ajmg.c.31617. Epub 2018 May 17.

Molecular testing in holoprosencephaly

Paul Kruszka  1 , Ariel F Martinez  1 , Maximilian Muenke  1
Affiliations
Meta-Analysis

Molecular testing in holoprosencephaly

Paul Kruszka et al. Am J Med Genet C Semin Med Genet. 2018 Jun.

Abstract

Holoprosencephaly (HPE) is a structural brain anomaly characterized by failure of the forebrain to separate during early embryogenesis. Both genetic and environmental etiologies of HPE have been discovered over the last three decades. Traditionally, the genetic workup for HPE has been a karyotype, chromosomal microarray, and/or Sanger sequencing of select genes. The recent increased availability of next-generation sequencing has changed the molecular diagnostic landscape for HPE, associating new genes with this disorder such as FGFR1. We conducted a systematic review of the medical literature for the molecular testing of HPE for studies published in the last 20 years. We also queried known commercial diagnostic laboratories and used information on their websites to construct a list of available commercial testing. Our group released its first recommendations in 2010 and this update incorporates the technology shifts and gene discoveries over the last decade. These recommendations provide a guide for genetic diagnosis of HPE, which is paramount for patients and their families for prognosis, treatment, and genetic counseling.

Keywords: commercial laboratories; holoprosencephaly; molecular testing; next-generation sequencing.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Figure 1
Figure 1
Recommended genetic testing for individual with holoprosencephaly. Targeted testing should be done on cases with clincal exam findings consistent with a syndromic etiology. The last step of trio-case whole exome sequencing or whole genome sequencing has not been evaluated critically in the medical literature but is a consideration based on experience of clinician.
See this image and copyright information in PMC

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