Holoprosencephaly

Overview

  • EPIC Code:
  • Soft Test Code:
  • MSOT
Included Tests

SHH (sonic hedgehog); SIX3 ( homolog of Drosophila So); TGIF (TG-interacting factor); ZIC2 (homolog of Drosophila Opa) 


Clinical Significance

Holoprosencephaly (HPE) is etiologically heterogeneous, with genetic factors, maternal host factors, and possible environmental factors contributing. Chromosome anomalies underlie up to half of HPE, including trisomy of chromosomes 13 or 18, and various structural anomalies of several chromosomes. Submicroscopic deletion involving HPE-related genes have been identified by FISH in another 5% of individuals with HPE [Muenke, unpublished]. Approximately 18-25% of individuals with HPE associated with a single-gene disorder have a recognizable syndrome (e.g. Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome), while the remainder have HPE not associated with a recognizable syndrome. Of the nonsyndromic HPE patients, the literature suggests that approximately 13% of patients will be found to have a mutation in the SHH, TGIF, SIX3, or ZIC2 gene, which usually behave in an autosomal dominant manner.

Bi-directional sequence analysis of four genes involved in holoprosencephaly is offered by GeneDx as follows. Using genomic DNA obtained from the submitted sample, bi-directional DNA sequence of most of the coding portion of the SHH gene (3 exons), the TGIF gene (3 exons), the SIX3 gene (2 exons), and the ZIC2 gene (3 exons) is obtained and analyzed. Carrier testing in other family members and prenatal diagnosis is available once the mutation in a family has been defined. Due to the possibility of complete deletion of one copy of any of these genes in association with holoprosencephaly, CopyDx analysis to detect copy number is being developed for patients in whom no heterozygous positions are identified on sequence analysis. Call for further information.


Specimen Collection & Preparation

Client Notes

Contact the Laboratory at 66-1500 (Option 1) for the Payment requirements of this test.


Specimen Requirements

Two - 3.0 to 5.0 mL in Whole Blood in a Lavender Top Tubes - EDTA 

Pediatric requirements: 1.0 to 2.0 mL Whole Blood in a Lavender Top Tube - EDTA


Transport And Storage

Refrigerated


Collection Instructions


Minimum Volume


Neonatal Volume

Clinical Interpretation

Reference Range:

Not Applicable


Methodology:
  • Bi-directional sequence analysis
Clinical Significance

Holoprosencephaly (HPE) is etiologically heterogeneous, with genetic factors, maternal host factors, and possible environmental factors contributing. Chromosome anomalies underlie up to half of HPE, including trisomy of chromosomes 13 or 18, and various structural anomalies of several chromosomes. Submicroscopic deletion involving HPE-related genes have been identified by FISH in another 5% of individuals with HPE [Muenke, unpublished]. Approximately 18-25% of individuals with HPE associated with a single-gene disorder have a recognizable syndrome (e.g. Pallister-Hall syndrome, Smith-Lemli-Opitz syndrome), while the remainder have HPE not associated with a recognizable syndrome. Of the nonsyndromic HPE patients, the literature suggests that approximately 13% of patients will be found to have a mutation in the SHH, TGIF, SIX3, or ZIC2 gene, which usually behave in an autosomal dominant manner.

Bi-directional sequence analysis of four genes involved in holoprosencephaly is offered by GeneDx as follows. Using genomic DNA obtained from the submitted sample, bi-directional DNA sequence of most of the coding portion of the SHH gene (3 exons), the TGIF gene (3 exons), the SIX3 gene (2 exons), and the ZIC2 gene (3 exons) is obtained and analyzed. Carrier testing in other family members and prenatal diagnosis is available once the mutation in a family has been defined. Due to the possibility of complete deletion of one copy of any of these genes in association with holoprosencephaly, CopyDx analysis to detect copy number is being developed for patients in whom no heterozygous positions are identified on sequence analysis. Call for further information.


Production Schedule

Days Performed
Monday
Tuesday
Wednesday
Thursday
Friday
Departments
  • Sendouts - Miscellaneous

Coding & Compliance

CDM

00913334


CPT Coding

83891