Pitt-Hopkins-like syndrome-1 and Pitt-Hopkins-like syndrome-2 are inherited in an autosomal recessive manner and are caused by mutations in the genes CNTNAP2 (7q35) and NRXN1 (2p16.3) respectively. Both of these conditions resemble Pitt-Hopkins syndrome, caused by mutation of the TCF4 gene, with regard to the distinctive facial features, severe intellectual disability and breathing abnormalities; however, there is a phenotypical difference. While speech is severely impaired, individuals with mutation the CNTNAP2 or NRXN1 gene have normal or mildly delayed motor milestones.
Please note that this test is for the CNTNAP2 gene only.
Cortical Dysplasia-Focal Epilepsy Syndrome
In Old Order Amish children, Strauss et al. (2006) identified a homozygous mutation of the CNTNAP2 gene (7q35-q36) that causes focal epilepsy, cortical dysplasia, reduced deep-tendon reflexes, and relative macrocephaly. The focal seizures begin in early childhood and do not respond to therapy. After the onset of seizures, language regression, hyperactivity, intellectual disability, and impulsive and aggressive behavior are observed.
For patients with suspected CNTNAP2-related disorders, sequence analysis is recommended as the first step in mutation identification. For patients in whom mutations are not identified by full gene sequencing, deletion/duplication analysis is appropriate.
- Confirmation of a clinical diagnosis of CNTNAP2-related disorders.
- Carrier testing in adults with a family history of CNTNAP2-related disorders.
Analytical Sensitivity: ~99%
Submit only 1 of the following specimen types
Preferred specimen type: Whole Blood
Type: Whole Blood
Specimen Requirements:In EDTA (purple top) tube:
Infants (<2 years): 2-3 ml
Children (>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.
Specimen Requirements:OrageneTM Saliva Collection kit (available through EGL) 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.
- Deletion/duplication analysis of the CNTNAP2 gene by CGH array is available for those individuals in whom sequence analysis is negative.
- Sequencing and deletion/duplication analysis of the TCF4 and NRXRN1 genes are available.
- Custom diagnostic mutation analysis (KM) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.
- Prenatal testing is available only for known familial mutations to individuals who are confirmed carriers of mutations. Please contact the laboratory genetic counselor to discuss appropriate testing prior to collecting a prenatal specimen.