Costello Syndrome

Costello syndrome is a complex developmental disorder characterized by short stature, mental retardation, facial dysmorphism, cardiovascular abnormalities, musculoskeletal abnormalities and tumor predisposition. Costello syndrome may present in utero with polyhydramnios, edema, and fetal overgrowth. After birth, feeding difficulties, failure to thrive, and mild to moderate developmental and growth delay are common. The facial features are typically coarse, with a wide forehead, epicanthal folds, depressed nasal bridge, low-set ears with large, thick lobes, and thick lips. About 63% of patients have cardiovascular malformations, most commonly pulmonic stenosis, hypertrophic cardiomyopathy, and tachyarrhythmia (Lin et al. 2002). The hair may be curly and the skin dark-colored, soft and lax, especially on the neck, palms and soles. Hands and feet are fleshy with deep palmar and plantar creases, and hyperextensible digits. During childhood, patients progressively develop benign skin tumors (papillomata) around the mouth, nose and anus. While these tumors are benign, 10%-15% of patients with Costello syndrome will also develop malignant tumors, such as rhabdomyosarcoma, neuroblastoma, ganglioneuroblastoma, and transitional carcinoma of the bladder.

Tests Available

Forms and Documents

Test Details

CBL, NRAS
  • Confirmation of a clinical diagnosis
  • To differentiate between the disorders of the Noonan syndrome spectrum
  • Recurrence risk
  • Next-Gen Sequencing

Ordering

535
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81404x1, 81479x2
No
Yes
  • 759.8 Other specified anomalies
  • 744.9 Unspecified anomalies of face and neck Congenital: anomaly NOS of face [any part] or neck [any part] deformity, NOS of face [any part] or neck [any part]
* For price inquiries please email zebras@genedx.com

References

  1. Cordeddu Nat Genet 41:1022-1026, 2009
  2. Gripp KW et al. Am J Med Genet A. 140:1-7, 2006
  3. Kerr B et al. J Med Genet. 43:401-5, 2006
  4. Lin AE et al. Am J Med Genet. 111:115-29, 2002
  5. White SM. Am J Med Genet A. 136:128-35, 2005
  6. Tartaglia M et al. Am J Hum Genet 70:1555-63, 2002
  7. Tartaglia & Gelb. Ann Rev Genomics Hum Genet 6:45-68, 2005
  8. Schubbert et al., Nature Genetics 38:331-336, 2006
  9. Carta C et al. Am J Hum Genet 79:129-135, 2006
  10. Roberts et al. Nat Genet 39:70-4, 2007
  11. Tartaglia et al. Nat Genet. 39:75-9, 2007
  12. Pandit B et al. Nat Genet. 39: 1007-12, 2007
  13. Razzaque MA et al. Nat Genet. 39:1013-17, 2007
  14. Rodriguez- Viciana, et al. Science 311:1287-90, 2006
  15. Niihori, et al. Nature Genetics. 38: 294-296, 2006
  16. Narumi et al. Am J Med Genet, 143:799-809, 2007
  17. Aoki Y et al. Nat Genet. 37:1038-40, 2005
  18. Costello JM. Am J Med Genet. 62:199-201, 1996
  19. Estep AL et al. Am J Med Genet A. 140:8-16, 2006
  20. Gripp KW. Am J Med Genet C Semin Med Genet. 137:72-7, 2005

Forms and Documents

Test Details

HRAS
  • Confirmation of a clinical diagnosis
  • To differentiate between the disorders of the Noonan syndrome spectrum
  • Recurrence risk
  • Prenatal diagnosis
  • Capillary Sequencing

Ordering

191
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81404x1
No
Yes
  • 759.8 Other specified anomalies
  • 744.9 Unspecified anomalies of face and neck Congenital: anomaly NOS of face [any part] or neck [any part] deformity, NOS of face [any part] or neck [any part]
* For price inquiries please email zebras@genedx.com

References

  1. Cordeddu Nat Genet 41:1022-1026, 2009
  2. White SM. Am J Med Genet A. 136:128-35, 2005
  3. Kerr B et al. J Med Genet. 43:401-5, 2006
  4. Lin AE et al. Am J Med Genet. 111:115-29, 2002
  5. Gripp KW et al. Am J Med Genet A. 140:1-7, 2006
  6. Estep AL et al. Am J Med Genet A. 140:8-16, 2006
  7. Aoki Y et al. Nat Genet. 37:1038-40, 2005
  8. Niihori, et al. Nature Genetics. 38: 294-296, 2006
  9. Narumi et al. Am J Med Genet, 143:799-809, 2007
  10. Razzaque MA et al. Nat Genet. 39:1013-17, 2007
  11. Rodriguez- Viciana, et al. Science 311:1287-90, 2006
  12. Pandit B et al. Nat Genet. 39: 1007-12, 2007
  13. Roberts et al. Nat Genet 39:70-4, 2007
  14. Carta C et al. Am J Hum Genet 79:129-135, 2006
  15. Schubbert et al., Nature Genetics 38:331-336, 2006
  16. Tartaglia & Gelb. Ann Rev Genomics Hum Genet 6:45-68, 2005
  17. Tartaglia M et al. Am J Hum Genet 70:1555-63, 2002
  18. Gripp KW. Am J Med Genet C Semin Med Genet. 137:72-7, 2005
  19. Costello JM. Am J Med Genet. 62:199-201, 1996
  20. Tartaglia et al. Nat Genet. 39:75-9, 2007

Forms and Documents

Test Details

A2ML1, ACTB, ACTG1, BRAF, CBL, HRAS, KAT6B, KRAS, LZTR1, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, SOS1, SOS2, SPRED1
  • Confirmation of a clinical diagnosis
  • To differentiate between the disorders of the Noonan syndrome spectrum
  • Recurrence risk
  • Next-Gen Sequencing

Ordering

534
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81442x1
Yes
Yes
  • 759.8 Other specified anomalies
  • 744.9 Unspecified anomalies of face and neck Congenital: anomaly NOS of face [any part] or neck [any part] deformity, NOS of face [any part] or neck [any part]
* For price inquiries please email zebras@genedx.com

References

  1. Tartaglia M et al. Am J Hum Genet 70:1555-63, 2002
  2. Tartaglia & Gelb. Ann Rev Genomics Hum Genet 6:45-68, 2005
  3. Schubbert et al., Nature Genetics 38:331-336, 2006
  4. Carta C et al. Am J Hum Genet 79:129-135, 2006
  5. Roberts et al. Nat Genet 39:70-4, 2007
  6. Tartaglia et al. Nat Genet. 39:75-9, 2007
  7. Pandit B et al. Nat Genet. 39: 1007-12, 2007
  8. Razzaque MA et al. Nat Genet. 39:1013-17, 2007
  9. Rodriguez- Viciana, et al. Science 311:1287-90, 2006
  10. Niihori, et al. Nature Genetics. 38: 294-296, 2006
  11. Narumi et al. Am J Med Genet, 143:799-809, 2007
  12. Aoki Y et al. Nat Genet. 37:1038-40, 2005
  13. Costello JM. Am J Med Genet. 62:199-201, 1996
  14. Estep AL et al. Am J Med Genet A. 140:8-16, 2006
  15. Gripp KW. Am J Med Genet C Semin Med Genet. 137:72-7, 2005
  16. Gripp KW et al. Am J Med Genet A. 140:1-7, 2006
  17. Kerr B et al. J Med Genet. 43:401-5, 2006
  18. Lin AE et al. Am J Med Genet. 111:115-29, 2002
  19. White SM. Am J Med Genet A. 136:128-35, 2005
  20. Cordeddu Nat Genet 41:1022-1026, 2009
  21. Clayton-Smith et al. (2011) Am J Hum Genet 89(5):675-681
  22. Campeau et al. (2012) Am J Hum Genet 90:282-289
  23. Simpson et al. (2012) Am J Hum Genet 90:290-294

Forms and Documents

Test Details

BRAF, HRAS, KRAS, MAP2K1, MAP2K2, NRAS, PTPN11, RAF1, RIT1, SHOC2, SOS1
  • Prenatal ultrasound findings suggestive of Noonan syndrome, including cystic hygroma
  • Fetus with ultrasound anomalies & parent with clinical diagnosis of Noonan syndrome
  • Next-Gen Sequencing

Ordering

357
2-3 weeks
20 mg CVS
20 mL Amniotic Fluid|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 Ug DNA Concentration

Billing

81404x1, 81405x2, 81406x3
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Achiron, et al (2000) Noonan Syndrome: A cryptic condition in early gestation. Am J Med Genet 92:159-165
  2. Adekunle, et al (1999) Increased first trimester nuchal translucency: pregnancy and infant outcomes after routine screening for Down’s syndrome in an unselected antenatal population. Br J Radiol 72:457-60
  3. Tartaglia, et al (2001) Mutations in PTPN11, encoding the protein tyrosine phosphatase SHP-2, cause Noonan syndrome. Nat Genet 29:465-8
  4. Trauffer, et al (1994) The natural history of euploid pregnancies with first-trimester cystic hygromas. Am J Obstet Gynecol 170:1279-84
  5. Benacerraf, et al (1989) The prenatal sonographic features of Noonan syndrome. J Ultrasound Med 8:59-63
  6. Ferguson et al. (2006) PTPN11 gene analysis in fetuses with abnormal ultrasound findings: The GeneDx experience. Poster presentation at the Cardiofaciocutaneous Syndrome & Noonan Syndrome International Symposium, Nov 17-19, 2006, Potomac, MD
  7. Hiippala, et al (2001) Fetal nuchal translucency and normal chromosomes: a long-term follow-up study. Ultrasound Obstet Gynecol 18:18-22
  8. Reynders, et al (1997) First trimester isolated fetal nuchal lucency: Significance and outcome. J Ultrasound Med 16:101-105
  9. Souka, et al (2001) Outcome of pregnancy in chromosomally normal fetuses with increased nuchal translucency in the first trimester. Ultrasound Obstet Gynecol 18:9-17
  10. Pandit B et al. (2007) Nat Genet 39:1007-1012. Lee et al. (2009) Clin Genet. 75(2):190-4