Test code: 10001

Macrocephaly and Overgrowth Syndromes: Sequencing Panel
Test Code: 10001
Turnaround time: 6 weeks

Condition description

Macrocephaly is defined as a head circumference, which is 2 standard deviations larger than the average when matched for age and sex. It refers to an abnormally large head inclusive of the scalp, cranial bone, and intracranial contents. Macrocephaly can arise due to a true enlargement of the brain (megalencephaly) or other conditions such as hydrocephalus and be either syndromic or non-syndromic. The genetic subtypes of macrocephaly include familial forms of macrocephaly, autism, syndromic associations such as PTEN hamartoma syndrome, Noonan syndrome, Sotos syndrome, and metabolic disorders such as glutaric aciduria type 1 and D-2-hydroxyglutaric aciduria.

Reference:
Williams et al. (2008). Am J Med Genet A. 146A: 2023–37.

GENES
AKT1, AKT2, AKT3, CDKN1C, CUL4B, DNMT3A, EZH2, GLI3, GNAQ, GPC3, MED12, MTOR, NFIX, NSD1, PHF6, PIK3CA, PIK3R2, PTCH1, PTEN, RNF135, UPF3B

INDICATIONS

This test is indicated for:

  • Patients with a clinical diagnosis of macrocephaly or other overgrowth syndrome.

METHODOLOGY

Next Generation Sequencing: In-solution hybridization of all coding exons is performed on the patient’s genomic DNA. Although some deep intronic regions may also be analyzed, this assay is not meant to interrogate most promoter regions, deep intronic regions, or other regulatory elements, and does not detect single or multi-exon deletions or duplications. Direct sequencing of the captured regions is performed using next generation sequencing. The patient’s gene sequences are then compared to a standard reference sequence. Potentially causative variants and areas of low coverage are Sanger-sequenced. Sequence variations are classified as pathogenic, likely pathogenic, benign, likely benign, or variants of unknown significance. Variants of unknown significance may require further studies of the patient and/or family members.

DETECTION

Next Generation Sequencing: Clinical Sensitivity: Unknown. Mutations in the promoter region, some mutations in the introns and other regulatory element mutations cannot be detected by this analysis. Large deletions/duplications will not be detected by this analysis. Results of molecular analysis should be interpreted in the context of the patient’s clinical/biochemical phenotype.

Analytical Sensitivity: ~99%

SPECIMEN REQUIREMENTS

Submit only 1 of the following specimen types

* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

Related Tests

  • Macrocephaly and Overgrowth Snydromes: Sequencing and Beckwith-Wiedemann Syndrome Methylation Panel (Test code: 9494)
  • Macrocephaly and Overgrowth Syndrome: Deletion/Duplication Panel (Test code: 1191)