Costello Syndrome
Gene: HRAS
Protein: GTPase HRas
Clinical Characteristics
- Feeding difficulty
- Postnatal short stature
- Characteristic facial features:
- Full lips and/or large mouth
- Coarse features
- Full cheeks
- Loose skin and deep palmar or plantar skin creases
- Curly or sparse, fine hair
- Deep, hoarse, or whispery voice
- Papillomas of face and perianal region - typically absent in infancy but may appear in childhood
- Characteristic hand posture:
- Splayed fingers
- Ulnar deviation of wrists
- Congenital heart problems:
- Most commonly pulmonic stenosis
- Hypertrophic cardiomyopathy
- Atrial tachycardia
- Increased occurrence of benign and malignant solid tumors
- Developmental delay or mental retardation
- Social, outgoing personality
Inheritance pattern: Autosomal dominant
What Can Be Learned From This Test
Testing is performed by sequencing exons 2 and 3 and the surrounding intronic regions of the HRAS gene. Sequencing of all coding exons can also be performed upon request. This assay will detect point mutations, small deletions and small insertions. It will not detect a partial or whole gene deletion or duplication.
HRAS is the only gene known to be associated with Costello syndrome. Sequence analysis of exon 2 detects a mutation in 80-90% of individuals with Costello syndrome. Mutations in other exons have also been reported. A negative test result does not rule out somatic mosaicism of an HRAS mutation, which has been described in individuals with Costello syndrome.
Costello syndrome is one of a group of related disorders caused by abnormal functioning of the Ras-mitogen-activated protein kinase (RAS/MapK) pathway. A negative HRAS test does not rule out all of these disorders, and additional testing may be indicated.
Sample Requirements
Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).
Turnaround time: 10-14 business days
CPT Codes and Cost
Full Gene Sequencing
- Code: 81404
- Cost: $500
Exons (2 & 3 Only)
- Code: 81403
- Cost: $225
Known Variant Testing
- Code: 81479
- Cost: $225