Stickler syndrome in the Czech Republic:
phenotypic variability and genetic heterogeneity

Czech version

Authors: Čopíková J. ¹; Katra R. ²; Pourová Kremlíková R. ¹
Authors‘ workplace: Ústav biologie a lékařské genetiky 2. LF UK a FN v Motole ¹; Klinika ušní, nosní a krční 2. LF UK a FN v Motole ²
Published in: Otorinolaryngol Foniatr, 70, 2021, No. 1, pp. 39-46.
Category: Review Article
doi: https://doi.org/10.48095/ccorl202139

Overview

Stickler syndrome (STL) is a progressive multisystemic disorder of connective tissue with an incidence of 1:7,500 newborns, which is probably underestimated due to its considerable clinical and genetic heterogeneity. STL symptoms include cleft palate or the Pierre-Robin sequence, hearing and/ or vision impairment, namely early high myopia and spontaneous retinal detachment, skeletal dysplasia, and a characteristic facial appearance, including a flat profile, protruding eyes, and micrognathia. STL symptoms show high inter- and even intrafamilial phenotypical variability. Variants in seven different collagen genes can cause STL. Autosomal dominant (AD) type 1 caused by a defect in the COL2A1 gene is the most common form of STL (80–90%); AD type 2 (involving COL11A1 gene defects) is much less common (10–20%). The third AD type and all autosomal recessive types are extremely rare. A genetically confirmed diagnosis of STL facilitates early treatment, prevention, and an accurate genetic risk estimation of STL in the family.

Keywords:

Stickler syndrome – collagen – myopia – Retinal detachment – Pierre-Robin sequence – hearing impairment – COL2A1

Sources

1. Van Camp G, Snoeckx RL, Hilgert N et al. A new autosomal recessive form of Stickler syndrome is caused by a mutation in the COL9A1 gene. Am J Hum Genet 2006; 79(3): 449–457. Doi: 10.1086/ 506478.

2. Nikopoulos K, Schrauwen I, Simon M et al. Autosomal recessive Stickler syndrome in two families is caused by mutations in the COL9A1 gene. Invest Ophthalmol Vis Sci 2011; 52(7): 4774–4779. Doi: 10.1167/ iovs.10-7128.

3. Baker S, Booth C, Fillman C et al. A loss of function mutation in the COL9A2 gene causes autosomal recessive Stickler syndrome. Am J Med Genet A 2011; 155A(7): 1668–1672. Doi: 10.1002/ ajmg.a.34071.

4. Faletra F, D‘Adamo AP, Bruno I et al. Autosomal recessive Stickler syndrome due to a loss of function mutation in the COL9A3 gene. Am J Med Genet A 2014; 164A(1): 42–47. Doi: 10.1002/ ajmg.a.36165.

5. Čopíková J, Paděrová J, Románková V et al. Expanding the phenotype spectrum associated with pathogenic variants in the COL2A1 and COL11A1 genes. Ann Hum Genet 2020; 84(5): 380–392. Doi: 10.1111/ ahg.12386.

6. Francomano CA. Stickler syndrome. In: Management of Genetic Syndromes. 3rd ed. Ed. Cassidy SB, Allanson JE. Baltimore, Meryland: John Wiley & Sons; 2010: 787–796.

7. Stickler GB, Belau PG, Farrell FJ et al. Hereditary progressive arthro-ophthalmopathy. Mayo Clin Proc 1965; 40: 433–455.

8. Stickler GB, Pugh DG. Hereditary progressive ophthalmopathy. II. Additional observations, a hearing defect and a report of a similar case. Mayo Clin Proc 1967; 42: 495–500.

9. Opitz JM, France T, Herrmann J et al. The Stickler syndrome. N Engl J Med 1972; 286(10): 546–547. Doi: 10.1056/ NEJM197203092861020.

10. Zlotogora J, Sagi M, Schuper A et al. Variability of Stickler syndrome. Am J Med Genet 1992; 42(3): 337–339. Doi: 10.1002/ ajmg.1320420316

11. Robin NH, Moran RT, Ala-Kokko L. Stickler syndrome. In: GeneReviews((R)). Ed. Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A. Seattle (WA); 1993.

12. Schreiner RL, McAlister WH, Marshall RE et al. Stickler syndrome in a pedigree of Pierre-Robin syndrome. Am J Dis Child 1973; 126(1): 86–90. Doi: 10.1001/ archpedi.1973.02110190074016.

13. Bush PG, Williams AJ. Incidence of the Robin Anomalad (Pierre-Robin syndrome). Br J Plast Surg 1983; 36(4): 434–437. Doi: 10.1016/ 0007-1226(83)90123-6.

14. Printzlau A, Andersen M. Pierre-Robin sequence in Denmark: a retrospective population-based epidemiological study. Cleft Palate Craniofac J 2004; 41(1): 47–52. Doi: 10.1597/ 02-055.

15. van den Elzen AP, Semmekrot BA, Bongers EM et al. Diagnosis and treatment of the Pierre-Robin sequence: results of a retrospective clinical study and review of the literature. Eur J Pediatr 2001; 160(1): 47–53. Doi: 10.1007/ s0043 10000646.

16. Holder-Espinasse M, Abadie V, Cormier-Daire V et al. Pierre-Robin sequence: a series of 117 consecutive cases. J Pediatr 2001; 139(4): 588–590. Doi: 10.1067/ mpd.2001.117784.

17. Snead MP, Yates JR. Clinical and molecular genetics of Stickler syndrome. J Med Genet 1999; 36(5): 353–359.

18. Stickler GB, Hughes W, Houchin P. Clinical features of hereditary progressive arthro-ophthalmopathy (Stickler syndrome): a survey. Genet Med 2001; 3(3): 192–196. Doi: 10.1097/ 00125817-200105000-00008.

19. Liberfarb RM, Levy HP, Rose PS et al. The Stickler syndrome: genotype/ phenotype correlation in 10 families with Stickler syndrome resulting from seven mutations in the type II collagen gene locus COL2A1. Genet Med 2003; 5(1): 21–27. Doi: 10.1097/ 00125817-200301000-00004.

20. Herrmann J, France TD, Spranger JW et al. The Stickler syndrome (hereditary arthroophthalmopathy). Birth Defects Orig Artic Ser 1975; 11(2): 76–103.

21. Snead MP, McNinch AM, Poulson AV et al. Stickler syndrome, ocular-only variants and a key diagnostic role for the ophthalmologist. Eye (Lond) 2011; 25(11): 1389–1400. Doi: 10.1038/ eye.2011.201.

22. Carroll C, Papaioannou D, Rees A et al. The clinical effectiveness and safety of prophylactic retinal interventions to reduce the risk of retinal detachment and subsequent vision loss in adults and children with Stickler syndrome: a systematic review. Health Technol Assess 2011; 15(16): iii–xiv, 1–62. Doi: 10.3310/ hta15160.

23. Temple IK. Stickler‘s syndrome. J Med Genet 1989; 26(2): 119–126. Doi: 10.1136/ jmg.26.2.119.

24. Seery CM, Pruett RC, Liberfarb RM et al. Distinctive cataract in the Stickler syndrome. Am J Ophthalmol 1990; 110(2): 143–148. Doi: 10.1016/ s0002-9394(14)76982-x.

25. Acke FR, Dhooge IJ, Malfait F et al. Hearing impairment in Stickler syndrome: a systematic review. Orphanet J Rare Dis 2012; 7: 84. Doi: 10.1186/ 1750-1172-7-84.

26. Nowak CB. Genetics and hearing loss: a review of Stickler syndrome. J Commun Disord 1998; 31(5): 437–453; 453–434. Doi: 10.1016/ s0021-9924(98)00015-x.

27. Admiraal RJ, Szymko YM, Griffith AJ et al. Hearing impairment in Stickler syndrome. Adv Otorhinolaryngol 2002; 61: 216–223. Doi: 10.1159/ 000066812.

28. Szymko-Bennett YM, Mastroianni MA, Shotland LI et al. Auditory dysfunction in Stickler syndrome. Arch Otolaryngol Head Neck Surg 2001; 127(9): 1061–1068. Doi: 10.1001/ archotol. 127.9.1061.

29. Rose PS, Ahn NU, Levy HP et al. Thoracolumbar spinal abnormalities in Stickler syndrome. Spine (Phila Pa 1976) 2001; 26(4): 403–409. Doi: 10.1097/ 00007632-200102150-00017.

30. Rai A, Wordsworth P, Coppock JS et al. Hereditary arthro-ophthalmopathy (Sticklersyndrome): a diagnosis to consider in familial premature osteoarthritis. Br J Rheumatol 1994; 33(12): 1175–1180. Doi: 10.1093/ rheu-matology/ 33.12.1175.

31. Liberfarb RM, Goldblatt A. Prevalence of mitral-valve prolapse in the Stickler syndrome. Am J Med Genet 1986; 24(3): 387–392. Doi: 10.1002/ ajmg.1320240302.

32. Ahmad N, Richards AJ, Murfett HC et al. Prevalence of mitral valve prolapse in Stickler syndrome. Am J Med Genet A 2003; 116A(3): 234–237. Doi: 10.1002/ ajmg.a.10619.

33. Poulson AV, Hooymans JM, Richards AJ et al. Clinical features of type 2 Stickler syndrome. J Med Genet 2004; 41(8): e107. Doi: 10.1136// jmg.2004.018382.

34. Higuchi Y, Hasegawa K, Yamashita M et al. A novel mutation in the COL2A1 gene in a patient with Stickler syndrome type 1: a case report and review of the literature. J Med Case Rep 2017; 11(1): 237. Doi: 10.1186/ s13256-017-1396-y.

35. Savasta S, Salpietro V, Sparta MV et al. Stickler syndrome associated with epilepsy: report of three cases. Eur J Pediatr 2015; 174(5): 697–701. Doi: 10.1007/ s00431-015-2514-8.

36. Gelse K, Poschl E, Aigner T. Collagens-structure, function, and biosynthesis. Adv Drug Deliv Rev 2003; 55(12): 1531–1546. Doi: 10.1016/ j.addr.2003.08.002.

37. Maumenee IH. Vitreoretinal degeneration as a sign of generalized connective tissue diseases. Am J Ophthalmol 1979; 88(3 Pt 1): 432–449. Doi: 10.1016/ 0002-9394(79)90645-7.

38. Baitner AC, Maurer SG, Gruen MB et al. The genetic basis of the osteochondrodysplasias. J Pediatr Orthop 2000; 20(5): 594–605. Doi: 10.1097/ 00004694-200009000-00010.

39. Godfrey M, Hollister DW. Type II achondrogenesis-hypochondrogenesis: identification of abnormal type II collagen. Am J Hum Genet 1988; 43(6): 904–913.

40. Annunen S, Korkko J, Czarny M et al. Splicing mutations of 54-bp exons in the COL11A1 gene cause Marshall syndrome, but other mutations cause overlapping Marshall/ Stickler phenotypes. Am J Hum Genet 1999; 65(4): 974–983. Doi: 10.1086/ 302585.

41. Jobling R, D‘Souza R, Baker N et al. The collagenopathies: review of clinical phenotypes and molecular correlations. Curr Rheumatol Rep 2014; 16(1): 394. Doi: 10.1007/ s11926-013-0394-3.

42. Nenna R, Turchetti A, Mastrogiorgio G et al. COL2A1 Gene mutations: mechanisms of spondyloepiphyseal dysplasia congenita. Appl Clin Genet 2019; 12: 235–238. Doi: 10.2147/ TACG.S197205.

43. Vikkula M, Mariman EC, Lui VC et al. Autosomal dominant and recessive osteochondrodysplasias associated with the COL11A2 locus. Cell 1995; 80(3): 431–437. Doi: 10.1016/ 0092-8674(95)90493-x.

44. Vuoristo MM, Pappas JG, Jansen V et al. A stop codon mutation in COL11A2 induces exon skipping and leads to non-ocular Stickler syndrome. Am J Med Genet A 2004; 130A(2): 160–164. Doi: 10.1002/ ajmg.a.30111.

45. Hanson-Kahn A, Li B, Cohn DH et al. Autosomal recessive Stickler syndrome resulting from a COL9A3 mutation. Am J Med Genet A 2018; 176(12): 2887–2891. Doi: 10.1002/ ajmg.a.40647.

46. Alzahrani F, Al Hazzaa SA, Tayeb H et al. LOXL3, encoding lysyl oxidase-like 3, is mutated in a family with autosomal recessive Stickler syndrome. Hum Genet 2015; 134(4): 451–453. Doi: 10.1007/ s00439-015-1531-z.

47. Chan TK, Alkaabi MK, ElBarky AM et al. LOXL3 novel mutation causing a rare form of autosomal recessive Stickler syndrome. Clin Genet 2019; 95(2): 325–328. Doi: 10.1111/ cge.13465.