Campomelic Dysplasia (CD)

Campomelic dysplasia (CD) is a rare, often lethal skeletal dysplasia characterized by angular bowing and shortening of the long bones, severe respiratory distress, and XY sex reversal. It is caused by chromosome abnormalities or mutations affecting expression of the SOX9 gene located on chromosome 17q24.3-q25.1. Approximately 75% of patients with CD that have a 46,XY karyotype exhibit partial or complete sex reversal, ranging from ambiguous genitalia to normal female external genitalia. In addition to bowing of the long bones, skeletal features of CD include club feet, a bell-shaped and underdeveloped thorax, eleven pairs of ribs, and hypoplastic scalpulae. CD is also associated with distinctive facial features including micrognathia, midfacial hypoplasia, a long philtrum, depressed nasal bridge, hypertelorism, and Pierre Robin cleft palate. Macrocephaly, congenital heart defects, absence of the olfactory bulbs, renal malformations, and pancreatic abnormalities have also been reported. Many infants die shortly after birth from respiratory compromise due to cervical spine instability, laryngotracheomalacia, hypoplastic lungs, and/or narrow airways. Children who survive the neonatal period often develop hearing loss, developmental delay, short stature, and progressive kyphoscoliosis. A small subgroup of patients with CD lack significant bowing of the limbs and are described as having acampomelic campomelic dysplasia (ACD). Patients with ACD have other typical features of campomelic dysplasia, and in some cases radiographs may reveal mild campomelia.

Tests Available

Forms and Documents

Test Details

SOX9
  • Full sequencing and deletion/duplication testing for fetuses with ultrasound findings suggestive of CD
  • Mutation-specific testing for fetuses with a family history of a known SOX9 mutation
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

3383
2-3 weeks
20 mL Amniotic Fluid
20 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|3 Ug DNA Concentration

Billing

81479x1, 81265x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Mansour et al., (1995) J Med Genet 32:415-420
  2. Mansour et al., (2002) J Med Genet 39:597-602
  3. Wagner et al., (Cell) 79:1111-1120
  4. Cameron et al., (1996) Hum Mol Genet 5(10):1625-1630
  5. Smyk et al., (2007) Am J Med Genet 143A(8):866-870
  6. Pop et al., (2004) J Med Genet 41:e47
  7. Meyer et al., (1997) Hum Mol Genet 6(1):91-98
  8. Pop et al. (2005) Hum Genet 117:43-53
  9. Huang et al., (1999) Am J Med Genet 87:349-353
  10. Refai et al., (2010) Am J Med Genet A 152A:422-426
  11. Moog et al., (2001) Am J Med Genet 104:239-245

Forms and Documents

Test Details

SOX9
  • Confirmation of the clinical diagnosis
  • To differentiate CD from other skeletal dysplasias such as osteogenesis imperfecta (OI), thanatophoric dysplasia, spondyloepiphyseal dysplasia congenita, and others
  • Prenatal diagnosis for a known familial mutation
  • Prenatal diagnosis when ultrasound findings are suggestive of campomelic dysplasia
  • Capillary Sequencing

Ordering

338
4 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Dried Blood Spots|Buccal Swabs

Billing

81479x1
No
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Mansour et al., (1995) J Med Genet 32:415-420; Mansour et al., (2002) J Med Genet 39:597-602
  2. Wagner et al., (Cell) 79:1111-1120. Cameron et al., (1996) Hum Mol Genet 5(10):1625-1630
  3. Smyk et al., (2007) Am J Med Genet 143A(8):866-870
  4. Pop et al., (2004) J Med Genet 41:e47
  5. Meyer et al., (1997) Hum Mol Genet 6(1):91-98
  6. Pop et al. (2005) Hum Genet 117:43-53
  7. Huang et al., (1999) Am J Med Genet 87:349-353
  8. Refai et al., (2010) Am J Med Genet A 152A:422-426.Moog et al., (2001) Am J Med Genet 104:239-245

Forms and Documents

Test Details

AGPS, ARSE, COL1A1, COL1A2, COL2A1, CRTAP, DLL3, DYNC2H1, EBP, EVC, EVC2, FGFR2, FGFR3, FLNB, GNPAT, IFITM5, LEPRE1, NEK1, PEX7, PPIB, SLC26A2, SOX9, TRIP11
  • Prenatal diagnosis in a fetus based on ultrasound findings suggestive of a skeletal dysplasia
  • Prenatal diagnosis for known familial pathogenic variant(s) in at-risk pregnancies
  • Distinguish between causes and forms of skeletal dysplasias
  • Genetic counseling, especially regarding recurrence risk
  • Next-Gen Sequencing

Ordering

949
2-3 weeks
20 mL Amniotic Fluid
20 mg CVS|2 T25 flasks of cultured amniocytes|2 T25 flasks of cultured chorionic villi|4 Ug DNA Concentration

Billing

81404x2, 81408x2, 81265x1, 81479x2
Yes
No
* For price inquiries please email zebras@genedx.com

References

  1. Barkova, E et. al. (2014). Clinical Genetics,doi:10.1111/cge.12434 [doi]
  2. Nelson, DB et. al. (2014). Journal of Ultrasound in Medicine 33(6), 1085-1090.
  3. Noel, AE & Brown RN (2014). International Journal of Women\\\\\\\'s Health, 6, 489-500.
  4. Dighe, M, et. al. (2008). Radiographics 28(4), 1061-1077.
  5. Hatzaki, A et. al. (2011). American Journal of Medical Genetics, 155A(10), 2426-2435.
  6. Witters, I, Moerman, P & Fryns, JP (2008). Genetic Counseling (Geneva, Switzerland), 19(3), 267-275.
  7. Stratbucker, WB (2009). Pediatrics in Review, 30(3), 114-115.
  8. Valadares, ER, et. al (2014). Jornal De Pediatria, 90(6), 536-541.
  9. Krakow, D, et. al., (2009). Genetics in Medicine 11(2), 127-133.
  10. http://www.omim.org/entry/200600
  11. Mansour et al., (1995) J Med Genet 32:415-420.
  12. Mansour et al., (2002) J Med Genet 39:597-602.
  13. Pop et al. (2005) Hum Genet 117:43-53.
  14. Moog et al., (2001) Am J Med Genet 104:239-245.
  15. Pop et al., (2004) J Med Genet 41:e47.
  16. Meyer et al., (1997) Hum Mol Genet 6(1):91-98
  17. Braverman, N, Moser, A and Steinberg, S. (Updated September 13, 2012). Rhizomelic Chondrodysplasia Punctata Type 1. In: GeneReviews at GeneTests Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-20
  18. Gunay-Aygun, M, Gahl,W, and Heller,T (Updated April 24, 2014). Congenital Hepatic Fibrosis Overview. In: GeneReviews at GeneTests Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2015. Available a
  19. Peraita-Ezcurra M, et al. (2012) Gene. May 10;499(1):223-5.
  20. Baujat G, et al. (2007) Orphanet J Rare Dis. Jun 4;2:27.