Acro-Renal-Ocular syndrome

Duane-Radial Ray syndrome (DRRS) is characterized by the Duane eye anomaly and radial ray malformations of the limbs. The Duane anomaly is a congenital disorder of eye movement defined by the limited or absent ability to move the eye outward (abduction) and/or inward (adduction). Radial ray malformations observed in this syndrome can include triphalangeal thumbs, preaxial polydactyly, hypoplasia/aplasia of the thumbs, hypoplasia/aplasia of the radii, and shortening and radial deviation of the forearms. Acro-Renal-Ocular syndrome (AROS), which is allelic to DRRS, presents with radial ray malformations and Duane anomaly, along with other features such as ocular coloboma and renal abnormalities (renal hypoplasia, horseshoe kidney, vesico-utereral reflux, bladder diverticular, ectopia, and mild malrotation). The overlap between DRRS and AROS is appreciable, and each syndrome has a highly variable intra- and interfamilial clinical phenotype. Other less common features belonging to both syndromes include hearing loss, ear malformations, epicanthal folds and very rarely, heart defects (atrial and ventricular septal defects). The limb anomalies characteristic of DRRS/AROS overlap with two other clinically defined genetic syndromes: HoltOram syndrome (HOS), which is due to mutations in the TBX5 gene, and Townes-Brocks syndrome (TBS), caused by mutations in the SALL1 gene. Both DRRS/AROS and HOS are associated with upper limb malformations, hypoplasia/aplasia of the thumbs, and triphalanageal thumbs. Shared limb abnormalities observed in DRRS/AROS and TBS include preaxial polydactyl and triphalangeal thumbs. Genetic testing for all three disorders is available at GeneDx.

Tests Available

Forms and Documents

Test Details

SALL4
  • Full sequencing testing for fetuses with prenatal ultrasound findings suggestive of Duane-Radial Ray Syndrome / Acro-Renal-Ocular Syndrome
  • Mutation-specific testing for fetuses with a family history of a known SALL4 mutation
  • Capillary Sequencing

Ordering

408
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. Kohlhase, J. et al., Okihiro syndrome is caused by SALL4 mutations. Hum Mol Genet. 11:2979-2987, 2002
  2. Borozdin, W. et al., SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanism. J Med Genet. 41(9):e113, 2004
  3. Al-Baradie R. et al., Duane Radial Ray Syndrome (Okihiro Syndrome) Maps to 20q13 and Results from Mutations in SALL4, a New Member of the SAL Family. Am J Hum Genet. 71:1195-1199, 2002
  4. Kohlhase J. et al., Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide
  5. Borozdin, W. et al., Novel mutations in the gene SALL4 provide further evidence for acro-renalocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum. J Med Genet.41(8):e102, 2004
  6. Kohlhase, J. et al., SALL4 Mutations in Okihiro syndrome (Duane-Radial Ray Syndrome), Acro-Renal-Ocular Syndrome, and Related Disorders. Hum Mutat. 26:176-183, 2005
  7. Miertus, J. et al., A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome. Hum Genet. 119: 154-161, 2006

Forms and Documents

Test Details

SALL4
  • Confirmation of a clinical diagnosis
  • To differentiate DRRS/AROS from HOS, TBS, and other radial malformation syndromes
  • Risk assessment
  • Prenatal diagnosis in families with an affected child and known mutation
  • Capillary Sequencing
  • Exon Array CGH

Ordering

262E
3 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL)|Buccal Swabs

Billing

81479x1
No
Yes
  • 759.89 Other Congenital malformation syndromes affecting multiple systems
* For price inquiries please email zebras@genedx.com

References

  1. Kohlhase, J. et al., Okihiro syndrome is caused by SALL4 mutations. Hum Mol Genet. 11:2979-2987, 2002
  2. Borozdin, W. et al., SALL4 deletions are a common cause of Okihiro and acro-renal-ocular syndromes and confirm haploinsufficiency as the pathogenic mechanism. J Med Genet. 41(9):e113, 2004
  3. Al-Baradie R. et al., Duane Radial Ray Syndrome (Okihiro Syndrome) Maps to 20q13 and Results from Mutations in SALL4, a New Member of the SAL Family. Am J Hum Genet. 71:1195-1199, 2002
  4. Kohlhase J. et al., Mutations at the SALL4 locus on chromosome 20 result in a range of clinically overlapping phenotypes, including Okihiro syndrome, Holt-Oram syndrome, acro-renal-ocular syndrome, and patients previously reported to represent thalidomide
  5. Borozdin, W. et al., Novel mutations in the gene SALL4 provide further evidence for acro-renalocular and Okihiro syndromes being allelic entities, and extend the phenotypic spectrum. J Med Genet.41(8):e102, 2004
  6. Kohlhase, J. et al., SALL4 Mutations in Okihiro syndrome (Duane-Radial Ray Syndrome), Acro-Renal-Ocular Syndrome, and Related Disorders. Hum Mutat. 26:176-183, 2005
  7. Miertus, J. et al., A SALL4 zinc finger missense mutation predicted to result in increased DNA binding affinity is associated with cranial midline defects and mild features of Okihiro syndrome. Hum Genet. 119: 154-161, 2006

Forms and Documents

Test Details

NIPBL, SALL1, SALL4, TBX5, TP73L (TP63)
  • Prenatal diagnosis in a fetus based on ultrasound findings suggestive of a limb abnormality syndrome
  • Prenatal diagnosis for known familial mutation(s) in at-risk pregnancies
  • Distinguish between causes and forms of limb abnormality syndromes
  • Genetic counseling, especially regarding recurrence risk
  • Exon Array CGH
  • Next-Gen Sequencing

Ordering

937
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

81405x1, 81479x4, 81265x1
Yes
Yes
* For price inquiries please email zebras@genedx.com

References

  1. Urban M, et al. Am J Med Genet. 2001 Jul 22;102(1):73-5.
  2. Huang WH, Porto M. Obstet Gynecol. 2002 May;99(5 Pt 2):956-8.
  3. Clark DM, et al. Am J Med Genet A. 2012 Aug;158A(8):1848-56. doi: 10.1002/ajmg.a.35410. Epub 2012 Jun 27.
  4. Kohlhase (Updated May 2012). Townes-Brocks Syndrome. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. Available at http://www.genetests.org.
  5. Kohlhase (Updated January 2015). SALL4-Related Disorders. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-2010. available at http://www.genetests.org.
  6. Tongsong T, Chanprapaph P., J Clin Ultrasound. 2000; 28: 98–100.
  7. Sepulveda W, Enriquez G, Martinez JL, Mejia R., J Ultrasound Med. 2004; 23: 983–7.
  8. Sutton VR, van Bokhoven H. TP63-Related Disorders. 2010 Jun 8 [Updated 2015 Aug 6]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015.
  9. Kline et al. (1993) Am J Med Genet 47:1042-1049.
  10. McDermott, D. et al., Pediatr Res. 58: 981-86, 2005.
  11. Gillis et al. (2004) Am J Hum Genet 75:610-623.
  12. Borck et al. (2006) Hum Mutat 27:731-735.
  13. Minor et al. (2014) Gene537:279-284.
  14. Castronovo et al. (2010) Clin Genet 78:560-564.
  15. Niu et al. (2006) Prenat Diagn 26:1054-1057.
  16. Weichert et al. (2011) J Mat Fetal Neonat Med 24(7):978-982.
  17. Botzenhart, E. et al., Human Mutation 26:282, 2005.
  18. Miertus, J. et al., Hum Genet. 119: 154-161, 2006.
  19. Marlin, S. et al., Human Mutation 14: 377-386, 1999.
  20. Borozdin, W. et al., Human Mutation 867(Online) 2006.
  21. Borozdin, W. et al., J Med Genet. 41(9):e113, 2004.
  22. Kohlhase J. et al., J Med Genet. 40:473-478, 2003.
  23. Akrami, SM. et al. J Med Genet. 38:E44, 2001.
  24. Fan, C. et al. J Med Genet. 40:e29, 2003.
  25. Borozdin, W. et al. Hum Mutat. 27:975-976, 2006.