Chondrodysplasia Punctata (CDPX1)

X-linked recessive chondrodysplasia punctata (CDPX1) is characterized by abnormal cartilage and bone development, including nasomaxillary hypoplasia, absence of the anterior nasal spine, hypoplasia of distal phalanges (brachytelephalangy), stippled epiphyses on X-ray (chondrodysplasia punctata) especially in the hands and feet, hearing loss and short stature. CDPX1 has variable expression. Less severely affected individuals have normal intellect, minimal morbidity and may achieve normal stature in adulthood. More severe cases may involve marked nasal hypoplasia requiring choanal stents, punctate calcifications involving the tracheobronchial tree and leading to airway complications, as well as abnormal ossification of the cervical vertebrae resulting in cervical spine stenosis and instability, requiring close follow-up, surgical interventions and early lethality in some cases. Cardiac defects, mental retardation and seizure disorders have also been described.

Tests Available

Forms and Documents

Test Info Sheet Test Requisition

Test Details

  • Confirmation of a clinical diagnosis
  • Carrier testing in female relatives
  • Prenatal diagnosis in families with a defined mutation

Ordering

282E
4 weeks
2-5 mL Blood - Lavender Top Tube
Buccal Swabs

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.

Billing

81479x1
No
Yes
  • 756.59 Chondrodysplasia punctata epiphysealis
For price inquiries please email zebras@genedx.com

**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

References

  1. Brunetti-Pierri, N. et al. (2003) X-Linked Recessive Chondrodysplasia Punctata: Spectrum of Arylsulfatase E Gene Mutations and Expanded Clinical Variability Am J Med Genet 117A:164-168
  2. Sheffield, L.J. et al. (1998) Segregation of mutations in arylsulphatase E and correlation with the clinical presentation of chodrodysplasia punctata J Med Genet 35:1004-1008
  3. Franco B. et al. (1995) A Cluster of Sulfatase Genes on Xp22.3: Mutations in Chondrodysplasia Punctata(CDPX) and Implications for Warafin Embryopathy Cell 81:15-25.

Forms and Documents

Test Info Sheet Test Requisition Form

Test Details

ABCA12, ABHD5, ALDH3A2, ALOX12B, ALOXE3, AP1S1, ARSE, CASP14, CDSN, CERS3, CHST8, CLDN1, CSTA, CYP4F22, EBP, ELOVL4, FLG, FLG2, GJB2, GJB3, GJB4, GJB6, KDSR, KRT1, KRT10, KRT2, KRT9, LIPN, LOR, MBTPS2, NIPAL4, NSDHL, PEX7, PHGDH, PHYH, PNPLA1, POMP, PSAT1, SDR9C7, SERPINB8, SLC27A4, SNAP29, SPINK5, ST14, STS, TGM1, TGM5, VPS33B, ZMPSTE24
  • Identification of the specific molecular basis of congential ichthyosis or related skin disorders
  • Genetic counseling and recurrence risk assessment
  • Preparation for prenatal testing in future pregnancies

As needed, based on the referring diagnosis and coverage achieved by the XomeDxSlice-Ichthyosis for a given patient, critical exons with a high yield of mutations will be filled-in by dideoxy sequencing. For any autosomal recessive gene, if one definitive mutation is found by XomeDxSlice sequencing, AND the gene fits the type of ichthyosis reported by the referring physician, capillary sequencing will be used to fill in sequence for exons that are not sufficiently covered (>10X) to find the second mutation. If no second mutation is found by sequencing, deletion/duplication analysis of that gene can be performed at no additional cost can be performed at no additional cost.

Patient samples sent for XomeDxSlice will not be evaluated for secondary findings and therefore will not receive secondary findings as part of their result.

Ordering

708
6 weeks (4 weeks for newborns <1 month)
2-5 mL Blood - Lavender Top Tube
Buccal Swabs | Dried Blood Spots

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.

Billing

81252x1, 81401x1, 81479x1
Yes
Yes
For price inquiries please email zebras@genedx.com

**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

Forms and Documents

Test Requisition Test Info Sheet

Test Details

AGPS, ALPL, ARSE, BMP1, CEP120, COL11A1, COL11A2, COL1A1, COL1A2, COL2A1, COMP, CRTAP, DLL3, DYNC2H1, EBP, EVC, EVC2, FGFR1, FGFR2, FGFR3, FKBP10, FLNA, FLNB, GNPAT, HSPG2, IFITM5, IFT172, INPPL1, KIAA0586, LBR, LEPRE1(P3H1), LIFR, NEK1, PEX7, PLOD2, POR, PPIB, RUNX2, SERPINH1, SLC26A2, SLC35D1, SOX9, TMEM38B, TRIP11, TRPV4, TTC21B, WDR34, WDR35
  • 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

Ordering

949
3 weeks
20 mL Amniotic Fluid | 2 T25 flasks of cultured amniocytes | 20 mg CVS | 2 T25 flasks of cultured chorionic villi | Direct or Cultured POC
3 ug Extracted DNA

*Reporting times are typical, but could be extended in situations outside GeneDx's reasonable control.

Billing

81404x2, 81405x1, 81408x2, 81265x1
Yes
No
For price inquiries please email zebras@genedx.com

**The CPT codes provided are based on AMA guidelines and are for informational purposes only. CPT coding is the sole responsibility of the billing party. Please direct any questions regarding coding to the payer being billed.

References

  1. Geister et al. (2015) Annu Rev Genomics Hum Genet 16 :199-227 (PMID: 25939055)
  2. Colombi et al. (2017) Am. J. Med. Genet. A 173 (2):524-530 (PMID: 28102596)
  3. Nishimura et al. (2005) Human Mutation 26 (1):36-43 (PMID:15895462)
  4. Herman et al. (2002) Genetics In Medicine : Official Journal Of The American College Of Medical Genetics 4 (6):434-8 (PMID: 12509714)
  5. Hatzaki et al. (2011) Am. J. Med. Genet. A 155A (10):2426-35 (PMID: 21910223)
  6. Witters et al. (2008) Genet Couns. 19 (3):267-75 (PMID: 18990981).
  7. Pauli RM, Legare JM. Achondroplasia. 1998 Oct 12 [Updated 2018 May 10]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  8. Valadares et al. (2014) J Pediatr (Rio J) 90 (6):536-41 (PMID: 25046257)
  9. Krakow, D, et. al., (2009). Genetics in Medicine 11(2), 127-133. (PMID:19265753)
  10. Van Dijk et al. (2011) Mol Syndromol 2 (1):1-20 (PMID: 22570641)
  11. Mansour et al. (1995) Journal Of Medical Genetics 32 (6):415-20 (PMID: 7666392)
  12. Mansour et al. (2002) Journal Of Medical Genetics 39 (8):597-602 (PMID: 12161603)
  13. Robertson S. Otopalatodigital Spectrum Disorders. 2005 Nov 30 [Updated 2013 May 2]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  14. Robertson S. FLNB-Related Disorders. 2008 Oct 9 [Updated 2013 Oct 17]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  15. Itzkovitz et al. (2012) Hum. Mutat. 33 (1):189-97 (PMID: 21990100)
  16. Ladhani et al. (2013) Prenat. Diagn. 33 (11):1039-43 (PMID: 23836246)
  17. Braverman NE, Moser AB, Steinberg SJ. Rhizomelic Chondrodysplasia Punctata Type 1. 2001 Nov 16 [Updated 2012 Sep 13]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  18. Gunay-Aygun M, Gahl WA, Heller T. Congenital Hepatic Fibrosis Overview. 2008 Dec 9 [Updated 2014 Apr 24]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  19. Robin NH, Falk MJ, Haldeman-Englert CR. FGFR-Related Craniosynostosis Syndromes. 1998 Oct 20 [Updated 2011 Jun 7]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  20. Rauch et al. (2013) J. Med. Genet. 50 (1):21-4 (PMID: 23240094)
  21. Halbritter et al. (2013) American Journal Of Human Genetics 93 (5):915-25 (PMID: 24140113)
  22. Khalil et al. (2011) Prenat. Diagn. 31 (1):115-24 (PMID: 21210484)
  23. Huber et al. (2013) Am. J. Hum. Genet. 92 (1):144-9 (PMID: 23273569)
  24. Alby et al. (2015) Am. J. Hum. Genet. 97 (2):311-8 (PMID: 26166481)
  25. Sobreira et al. (2015) Am. J. Med. Genet. A 167A (1):159-63 (PMID: 25348816)
  26. Alanay et al. (2010) American Journal Of Human Genetics 86 (4):551-9 (PMID: 20362275)
  27. Mornet et al. (2008) Best Pract Res Clin Rheumatol 22 (1):113-27 (PMID: 18328985)
  28. Jackson et al. (2012) Human Mutation 33 (1):144-57 (PMID: 21922596)
  29. Mornet E, Nunes ME. Hypophosphatasia. 2007 Nov 20 [Updated 2016 Feb 4]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  30. Mornet et al. (2008) Best Pract Res Clin Rheumatol 22 (1):113-27 (PMID: 18328985)
  31. Jung et al. (2010) Clin. Genet. 77 (3):266-72 (PMID: 20447141)
  32. Unger S, Scherer G, Superti-Furga A. Campomelic Dysplasia. 2008 Jul 31 [Updated 2013 May 9]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  33. Braverman NE, Bober M, Brunetti-Pierri N, et al. Chondrodysplasia Punctata 1, X-Linked. 2008 Apr 22 [Updated 2014 Nov 20]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington; 1993-2018.
  34. Essawi et al. (2017) Mol Genet Genomic Med : (PMID: 29150909)
  35. Roosing et al. (2016) J. Med. Genet. 53 (9):608-15 (PMID: 27208211)
  36. Tompson et al. (2010) Am. J. Hum. Genet. 87 (5):708-12 (PMID: 21035103)
  37. Tompson et al. (2012) Am. J. Med. Genet. A 158A (2):309-14 (PMID: 22246659)
  38. Itzkovitz et al. (2012) Hum. Mutat. 33 (1):189-97 (PMID: 21990100)
  39. Morello et al. (2006) Cell 127 (2):291-304 (PMID: 17055431)
  40. Turnpenny PD et al. Spondylocostal Dysostosis, Autosomal Recessive. 2009 Aug 25 [Updated 2017 Dec 21]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington; 1993-2018.
  41. Dagoneau et al. (2009) American Journal Of Human Genetics 84 (5):706-11 (PMID: 19442771)
  42. D’Asdia et al. (2013) Eur J Med Genet 56 (2):80-7 (PMID: 23220543)
  43. El Hokayem et al. (2012) Journal Of Medical Genetics 49 (4):227-33 (PMID: 22499340) nek/dynch
  44. Zhou et al. (2014) PLoS ONE 9 (9):e107594 (PMID: 25238597)
  45. Huang et al. (2005) American Journal Of Human Genetics 76 (5):729-49 (PMID: 15793702)
  46. Machol K, Mendoza-Londono R, Lee B. Cleidocranial Dysplasia Spectrum Disorder. 2006 Jan 3 [Updated 2017 Nov 16]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  47. Bonafé L, Mittaz-Crettol L, Ballhausen D, et al. Achondrogenesis Type 1B. 2002 Aug 30 [Updated 2013 Nov 14]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
  48. Hiraoka et al. (2007) Nat. Med. 13 (11):1363-7 (PMID: 17952091)
  49. Furuichi et al. (2009) J. Med. Genet. 46 (8):562-8 (PMID: 19508970)
  50. Lv et al. (2016) J. Hum. Genet. 61 (6):539-45 (PMID: 26911354)
  51. Grigelioniene et al. (2013) Am. J. Med. Genet. A 161A (10):2554-8 (PMID: 23956106)
  52. Schindler A, Sumner C, Hoover-Fong JE. TRPV4-Associated Disorders. 2014 May 15. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2017.
  53. Davis et al. (2011) Nature Genetics 43 (3):189-96 (PMID: 21258341)
  54. Schmidts et al. (2013) Am. J. Hum. Genet. 93 (5):932-44 (PMID: 24183451)
  55. Duran et al. (2017) Cilia 6 :7 (PMID: 28400947)