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

Additional Information