Specimens should be shipped at room temperature in a leak-proof, rigid container with overnight delivery. To discuss minimum acceptable specimens for neonatal patients or for sample types not listed, please contact Allele Diagnostics.
- Peripheral whole blood in EDTA: 2-3 mL
Condition Description:Prader-Willi (PWS) syndrome is characterized by severe hypotonia and feeding difficulties in early infancy, followed in later infancy or early childhood by excessive eating and gradual development of obesity (unless externally controlled). Motor milestones and language development are delayed. All individuals have some degree of mental retardation. A distinctive behavioral phenotype (temper tantrums, stubbornness, and obsessive-compulsive characteristics) is common. Hypogonadism is present in both males and females and manifests as genital hypoplasia, incomplete pubertal development, and, in most, infertility. Short stature is common; characteristic facial features, strabismus, and scoliosis may be present.
Confirmation of a PWS diagnosis is obtained by DNA-based methylation testing to detect abnormal parent-specific imprinting within the Prader-Willi critical region (PWCR) on 15q11-13. This testing determines whether the region is maternally inherited only (the paternally contributed region is absent) and detects >99% of affected individuals. Methylation studies would also diagnose ~80% of patients with Angelman syndrome which is allelic (genetically related) to PWS, but clinically distinct, and results from the absence of maternally contributed region.
In all patients with a clinical presentation of PWS, it is important to begin testing with methylation studies first. If abnormal, further testing such as FISH (70% of the causes), uniparental disomy (UPD) studies (30%) and sequencing of the imprinting center (<1%) may be considered.
PWS is caused by absence of the paternally derived PWS/AS region of chromosome 15 by one of several genetic mechanisms. The risk to the sibs of an affected child of having PWS depends upon the genetic mechanism that resulted in the absence of the paternally contributed PWS/AS region. The risk to sibs is less than 1% if the affected child has a deletion or uniparental disomy, up to 50% if the affected child has a mutation of the imprinting control center, and up to 25% if a parental chromosomal translocation is present.
- Confirmation of a clinical diagnosis of PWS
Performed using methylation sensitive PCR.
Approximately 99% of PWS cases and approximately 70% of AS cases will be detected by this assay.
Normal: Both unmethylated and methylated allele detected. Prader-Willi Syndrome: Only methylated allele detected. Angelman Syndrome: Only unmethylated allele detected.