Increased Nuchal Translucency Testing Panel - conditions:

Tests for the most common genetic conditions that have been associated with increased nuchal translucency when aneuploidy has been ruled out:

Congenital Adrenal Hyperplasia

Prevalence: Approximately 1/15,000

21-hydroxylase deficiency (21-OHD) is the most common cause of congenital adrenal hyperplasia (CAH). CAH is a family of autosomal recessive conditions involving impaired synthesis of cortisol from cholesterol by the adrenal cortex. In 21-OHD CAH, excessive adrenal androgen biosynthesis results in virilization in all individuals and salt wasting in some. Newborns with salt wasting 21-OHD CAH are at risk for life threatening salt wasting crises. Prenatal treatment with dexamethasone is recommended to reduce the virilization of affected females.

The Increased Nuchal Translucency Testing Panel uses sequencing analysis to test for mutations and gene deletions in the CYP21A2 gene, and detects > 95% of cases of 21-OHD CAH associated with the CYP21A2 gene.

Noonan Syndrome

Prevalence: Approximately 1/1,000-1/2,500

Noonan syndrome (NS) is an autosomal dominant condition characterized by short stature, congenital heart defect, and developmental delay of variable degree. Other findings include broad or webbed neck, unusual chest shape, cryptorchidism, characteristic facies, varied coagulation defects, lymphatic dysplasias, and ocular abnormalities.

The Increased Nuchal Translucency Testing Panel uses arrayed primer extension (APEX) technology to test for mutations in all five genes known to be associated with NS, including PTPN11, KRAS, SOS1, RAF1, and MEK1, with a total detection of more than 70%.

Smith-Lemli-Opitz Syndrome

Prevalence: Approximately 1/20,000

Smith-Lemli-Opitz syndrome (SLO) is an autosomal recessive congenital multiple anomaly syndrome caused by an abnormality in cholesterol metabolism resulting from deficiency of the enzyme 7-dehydrocholesterol reductase. It is characterized by prenatal and postnatal growth retardation, microcephaly, moderate to severe mental retardation, and multiple major and minor malformations. These malformations include distinctive facial features, cleft palate, cardiac defects, underdeveloped external genitalia in males, postaxial polydactyly, and 2-3 syndactyly of the toes.

DHCR7 is the only gene known to be associated with SLO. The Increased Nuchal Translucency Testing Panel uses arrayed primer extension (APEX) technology to test for all of the reported mutations in the DHCR7 gene, with a detection rate of approximately 96%.

22q11.2 Deletion Syndrome (also known as DiGeorge Syndrome or Velocardiofacial Syndrome)

Prevalence: Approximately 1/4,000-1/6,000

Individuals with 22q11.2 deletion syndrome have a range of findings, including congenital heart defects (particularly conotruncal malformations), palatal abnormalities, characteristic facial features, learning difficulties, and immune deficiency. 22q11.2 deletion syndrome is inherited in an autosomal dominant manner, with approximately 93% of probands having a de novo deletion.

The Increased Nuchal Translucency Testing Panel uses arrayed primer extension (APEX) technology to test for polymorphisms across multiple loci to identify a deletion in the 22q11.2 region, with a detection of approximately 95%.

Spinal Muscular Atrophy

Prevalence: Approximately 1/7,000

Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by progressive muscle weakness resulting from degeneration and loss of anterior horn cells in the spinal cord and brain stem nuclei. Onset ranges from before birth to adolescence or young adulthood. Poor weight gain, sleep difficulties, pneumonia, scoliosis, and joint contractures are common complications.

The Increased Nuchal Translucency Testing Panel uses a PCR-based assay to determine the number of SMN1 gene copies, with a detection of approximately 94%.