Cardio-Facio-Cutaneous Syndrome

Cardio-facio-cutaneous (CFC) syndrome is characterized by cardiac defects, ectodermal abnormalities, developmental delay and facial dysmorphism. The ectodermal findings include sparse, slow-growing, curly hair, dry skin or ichthyosis, hyperkeratosis of the palms and soles, keratosis pilaris, eczema, hemangiomas, and hyperelastic skin. Typical dysmorphic features are macrocephaly, prominent forehead, hypertelorism, bitemporal constriction, posteriorly rotated ears, short bulbous nose with anteverted nares, hypoplastic supraorbital ridges, ptosis, and downslanting palpebral fissures. Webbing of the neck is seen in half the patients and cryptorchidism is observed in 43% of affected males. Ninety percent of patients have mental retardation (MR) ranging from mild to severe, with the majority having moderate MR. Short stature and postnatal growth deficiency are seen in 80% of patients, and failure to thrive is a common manifestation in early life. Congenital heart defects, the most frequent of which are pulmonic stenosis, atrial septal defects and hypertrophic cardiomyopathy, are seen in 80% of affected individuals.

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

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