Clinical Oral Investigations

, Volume 22, Issue 3, pp 1541–1549 | Cite as

Differences in maxillomandibular morphology among patients with mucopolysaccharidoses I, II, III, IV and VI: a retrospective MRI study

  • Till Koehne
  • Anja Köhn
  • Reinhard E. Friedrich
  • Uwe Kordes
  • Thorsten Schinke
  • Nicole Muschol
  • Bärbel Kahl-Nieke
Original Article



The aims of this study were to analyze the maxillomandibular morphology of patients with mucopolysaccharidosis (MPS) type I, II, III, IVa and VI and to evaluate the craniofacial effect of hematopoietic stem cell transplantation (HCST) in MPS I.

Materials and methods

One hundred head magnetic resonance images were retrospectively analyzed from 41 MPS and 27 control individuals. The width, height and length of the maxilla and mandible were plotted against age and the means of controls, MPS I, MPS II and MPS III were statistically compared. To determine the effect of HSCT in MPS I, jaw morphology was compared between MPS I patients with full donor chimerism versus patients with mixed/no donor chimerism.


Maxillary dimensions were not statistically different between the MPS types. The height and length of the mandible were clearly smaller in MPS I as compared to those in controls, MPS II and MPS III. This was associated with progressive resorption of the mandibular condyles in MPS I, which was also observed in MPS II and VI, but not in MPS III or IVa. Whereas the success of HCST did not affect these changes, mandibular width was significantly smaller in MPS I individuals with full donor chimerism.


MPS I individuals have a smaller mandible as compared to control, MPS II and MPS III individuals due to progressive condylar degeneration. These abnormalities are also evident following successful HSCT.

Clinical relevance

Clinicians should be aware of specific differences in mandibular morphology and condylar involvement among the MPS subtypes.


Mucopolysaccharidosis MRI Craniofacial Cephalometry OSAS Hematopoetic stem cell transplantation 



This research received no specific grant from any funding agency.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval

All analyses were performed retrospectively on routinely acquired images and all data were fully anonymized before analysis. Therefore, in accordance with the federal hospital laws (Hamburgisches Krankenhausgesetz) no approval by the local ethics committee was necessary.

Informed consent

For this type of study formal consent is not required.

Supplementary material

784_2017_2240_MOESM1_ESM.pdf (11.7 mb)
ESM 1 (PDF 11934 kb).


  1. 1.
    Muenzer J (2011) Overview of the mucopolysaccharidoses. Rheumatology (Oxford) 50(Suppl 5):v4–12. CrossRefGoogle Scholar
  2. 2.
    Tomatsu S, Fujii T, Fukushi M, Oguma T, Shimada T, Maeda M, Kida K, Shibata Y, Futatsumori H, Montano AM, Mason RW, Yamaguchi S, Suzuki Y, Orii T (2013) Newborn screening and diagnosis of mucopolysaccharidoses. Mol Genet Metab 110(1–2):42–53. CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Wraith JE (1995) The mucopolysaccharidoses: a clinical review and guide to management. Arch Dis Child 72(3):263–267CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Moore D, Connock MJ, Wraith E, Lavery C (2008) The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie and Scheie syndromes in the UK. Orphanet J Rare Dis 3:24. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    de Ru MH, Boelens JJ, Das AM, Jones SA, van der Lee JH, Mahlaoui N, Mengel E, Offringa M, O'Meara A, Parini R, Rovelli A, Sykora KW, Valayannopoulos V, Vellodi A, Wynn RF, Wijburg FA (2011) Enzyme replacement therapy and/or hematopoietic stem cell transplantation at diagnosis in patients with mucopolysaccharidosis type I: results of a European consensus procedure. Orphanet J Rare Dis 6:55. CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Stevenson RE, Howell RR, McKusick VA, Suskind R, Hanson JW, Elliott DE, Neufeld EF (1976) The iduronidase-deficient mucopolysaccharidoses: clinical and roentgenorgraphic features. Pediatrics 57(1):111–122PubMedGoogle Scholar
  7. 7.
    Clarke LA (1993) Mucopolysaccharidosis type I. In: Pagon RA, Adam MP, Ardinger HH et al. (eds) GeneReviews(R). Seattle (WA)Google Scholar
  8. 8.
    Ribeiro EM, Fonteles CS, Freitas AB, da Silva Alves KS, Monteiro AJ, da Silva CA (2015) A clinical multicenter study of orofacial features in 26 Brazilian patients with different types of mucopolysaccharidosis. Cleft Palate Craniofac J 52(3):352–358. CrossRefPubMedGoogle Scholar
  9. 9.
    Kim JH, Guilleminault C (2011) The nasomaxillary complex, the mandible, and sleep-disordered breathing. Sleep Breath 15(2):185–193. CrossRefPubMedGoogle Scholar
  10. 10.
    Pal AR, Brown N, Jones SA, Bigger BW, Bruce IA (2015) Obstructive sleep apnea in MPS: a systematic review of pretreatment and posttreatment prevalence and severity. J Inborn Errors Metab Screen 1-10. DOI: 10.1177/2326409815616392. Google Scholar
  11. 11.
    Fonseca FR, de Santana Sarmento DJ, Vasconcelos Medeiros PF, Diniz DN, dos Santos MT (2014) Patients with mucopolysaccharidosis have tendencies towards vertical facial growth. J Oral Maxillofac Surg 72(12):2539–2546. CrossRefPubMedGoogle Scholar
  12. 12.
    Kantaputra PN, Kayserili H, Guven Y, Kantaputra W, Balci MC, Tanpaiboon P, Tananuvat N, Uttarilli A, Dalal A (2014) Clinical manifestations of 17 patients affected with mucopolysaccharidosis type VI and eight novel ARSB mutations. Am J Med Genet A 164A(6):1443–1453. CrossRefPubMedGoogle Scholar
  13. 13.
    Keith O, Scully C, Weidmann GM (1990) Orofacial features of Scheie (Hurler-Scheie) syndrome (alpha-L-iduronidase deficiency). Oral Surg Oral Med Oral Pathol 70(1):70–74CrossRefPubMedGoogle Scholar
  14. 14.
    Zafeiriou DI, Batzios SP (2013) Brain and spinal MR imaging findings in mucopolysaccharidoses: a review. AJNR Am J Neuroradiol 34(1):5–13. CrossRefPubMedGoogle Scholar
  15. 15.
    Savara BS, Tracy WE (1967) Norms of size and annual increments for five anatomical measures of the mandible in boys from three to sixteen years of age. Arch Oral Biol 12(4):469–486CrossRefPubMedGoogle Scholar
  16. 16.
    Savara BS, Singh IJ (1968) Norms of size and annual increments of seven anatomical measures of maxillae in boys from three to sixteen years of age. Angle Orthod 38(2):104–120.<0104:NOSAAI>2.0.CO;2 PubMedGoogle Scholar
  17. 17.
    Khan F, Agarwal A, Agrawal S (2004) Significance of chimerism in hematopoietic stem cell transplantation: new variations on an old theme. Bone Marrow Transplant 34(1):1–12. CrossRefPubMedGoogle Scholar
  18. 18.
    Bromberg BE, Pasternak R, Walden RH, Rubin LR (1961) Evaluation of micrognathia with emphasis on late development of the mandible. Plast Reconstr Surg Transplant Bull 28:537–548CrossRefPubMedGoogle Scholar
  19. 19.
    Mandell DL, Yellon RF, Bradley JP, Izadi K, Gordon CB (2004) Mandibular distraction for micrognathia and severe upper airway obstruction. Arch Otolaryngol Head Neck Surg 130(3):344–348. CrossRefPubMedGoogle Scholar
  20. 20.
    Pal AR, Langereis EJ, Saif MA, Mercer J, Church HJ, Tylee KL, Wynn RF, Wijburg FA, Jones SA, Bruce IA, Bigger BW (2015) Sleep disordered breathing in mucopolysaccharidosis I: a multivariate analysis of patient, therapeutic and metabolic correlators modifying long term clinical outcome. Orphanet J Rare Dis 10:42. CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Ziyaeifard M, Azarfarin R, Ferasatkish R, Dashti M (2014) Management of difficult airway with laryngeal mask in a child with mucopolysaccharidosis and mitral regurgitation: a case report. Res Cardiovasc Med 3(2):e17456. PubMedPubMedCentralGoogle Scholar
  22. 22.
    Walker R, Belani KG, Braunlin EA, Bruce IA, Hack H, Harmatz PR, Jones S, Rowe R, Solanki GA, Valdemarsson B (2013) Anaesthesia and airway management in mucopolysaccharidosis. J Inherit Metab Dis 36(2):211–219. CrossRefPubMedGoogle Scholar
  23. 23.
    Nakamura T, Miwa K, Kanda S, Nonaka K, Anan H, Higash S, Beppu K (1992) Rosette formation of impacted molar teeth in mucopolysaccharidoses and related disorders. Dentomaxillofac Radiol 21(1):45–49. CrossRefPubMedGoogle Scholar
  24. 24.
    MacLeod SP, Macintyre DR (1993) Bilateral hypoplasia of mandibular condyles in Hurler’s syndrome. Oral Surg Oral Med Oral Pathol 75(5):659–660CrossRefPubMedGoogle Scholar
  25. 25.
    Schmidt H, Ullrich K, von Lengerke HJ, Kleine M, Bramswig J (1987) Radiological findings in patients with mucopolysaccharidosis I H/S (Hurler-Scheie syndrome). Pediatr Radiol 17(5):409–414CrossRefPubMedGoogle Scholar
  26. 26.
    McGovern E, Owens L, Nunn J, Bolas A, Meara AO, Fleming P (2010) Oral features and dental health in Hurler syndrome following hematopoietic stem cell transplantation. Int J Paediatr Dent 20(5):322–329. CrossRefPubMedGoogle Scholar
  27. 27.
    Downs AT, Crisp T, Ferretti G (1995) Hunter’s syndrome and oral manifestations: a review. Pediatr Dent 17(2):98–100PubMedGoogle Scholar
  28. 28.
    de Almeida-Barros RQ, Oka SC, Pordeus AC, de Medeiros PF, Bento PM, Godoy GP (2012) Oral and systemic manifestations of mucopolysaccharidosis type VI: a report of seven cases. Quintessence Int 43(3):e32–e38PubMedGoogle Scholar
  29. 29.
    de Santana Sarmento DJ, de Carvalho SH, Melo SL, Fonseca FR, Diniz DN, Bento PM, Mesquita Gde Q, de Melo DP (2015) Mucopolysaccharidosis: radiographic findings in a series of 16 cases. Oral Surg Oral Med Oral Pathol Oral Radiol 120(6):e240–e246. CrossRefPubMedGoogle Scholar
  30. 30.
    Cavaleiro RM, Pinheiro M, Pinheiro LR, Tuji FM, Feio Pdo S, de Souza IC, Feio RH, de Almeida SC, Schwartz IV, Giugliani R, Pinheiro JJ, Santana-da-Silva LC (2013) Dentomaxillofacial manifestations of mucopolysaccharidosis VI: clinical and imaging findings from two cases, with an emphasis on the temporomandibular joint. Oral Surg Oral Med Oral Pathol Oral Radiol 116(2):e141–e148. CrossRefPubMedGoogle Scholar
  31. 31.
    Sela M, Eidelman E, Yatziv S (1975) Oral manifestations of Morquio’s syndrome. Oral Surg Oral Med Oral Pathol 39(4):583–589CrossRefPubMedGoogle Scholar
  32. 32.
    Rolling I, Clausen N, Nyvad B, Sindet-Pedersen S (1999) Dental findings in three siblings with Morquio’s syndrome. Int J Paediatr Dent 9(3):219–224CrossRefPubMedGoogle Scholar
  33. 33.
    Wolford LM (2001) Idiopathic condylar resorption of the temporomandibular joint in teenage girls (cheerleaders syndrome). Proc (Bayl Univ Med Cent) 14(3):246–252CrossRefGoogle Scholar
  34. 34.
    Proffit WR, Vig KW, Turvey TA (1980) Early fracture of the mandibular condyles: frequently an unsuspected cause of growth disturbances. Am J Orthod 78(1):1–24CrossRefPubMedGoogle Scholar
  35. 35.
    Fjeld M, Arvidsson L, Smith HJ, Flato B, Ogaard B, Larheim T (2010) Relationship between disease course in the temporomandibular joints and mandibular growth rotation in patients with juvenile idiopathic arthritis followed from childhood to adulthood. Pediatr Rheumatol Online J 8:13. CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Sidiropoulou-Chatzigianni S, Papadopoulos MA, Kolokithas G (2001) Dentoskeletal morphology in children with juvenile idiopathic arthritis compared with healthy children. J Orthod 28(1):53–58. CrossRefPubMedGoogle Scholar
  37. 37.
    Schmidt M, Breyer S, Lobel U, Yarar S, Stucker R, Ullrich K, Muller I, Muschol N (2016) Musculoskeletal manifestations in mucopolysaccharidosis type I (hurler syndrome) following hematopoietic stem cell transplantation. Orphanet J Rare Dis 11(1):93. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Aldenhoven M, Boelens JJ, de Koning TJ (2008) The clinical outcome of hurler syndrome after stem cell transplantation. Biol Blood Marrow Transplant 14(5):485–498. CrossRefPubMedGoogle Scholar
  39. 39.
    Field RE, Buchanan JA, Copplemans MG, Aichroth PM (1994) Bone-marrow transplantation in Hurler’s syndrome. Effect on skeletal development. J Bone Joint Surg Br 76(6):975–981CrossRefPubMedGoogle Scholar
  40. 40.
    Souillet G, Guffon N, Maire I, Pujol M, Taylor P, Sevin F, Bleyzac N, Mulier C, Durin A, Kebaili K, Galambrun C, Bertrand Y, Froissart R, Dorche C, Gebuhrer L, Garin C, Berard J, Guibaud P (2003) Outcome of 27 patients with Hurler’s syndrome transplanted from either related or unrelated haematopoietic stem cell sources. Bone Marrow Transplant 31(12):1105–1117. CrossRefPubMedGoogle Scholar
  41. 41.
    Kuehn SC, Koehne T, Cornils K, Markmann S, Riedel C, Pestka JM, Schweizer M, Baldauf C, Yorgan TA, Krause M, Keller J, Neven M, Breyer S, Stuecker R, Muschol N, Busse B, Braulke T, Fehse B, Amling M, Schinke T (2015) Impaired bone remodeling and its correction by combination therapy in a mouse model of mucopolysaccharidosis-I. Hum Mol Genet 24(24):7075–7086. PubMedGoogle Scholar
  42. 42.
    Hartung SD, Frandsen JL, Pan D, Koniar BL, Graupman P, Gunther R, Low WC, Whitley CB, McIvor RS (2004) Correction of metabolic, craniofacial, and neurologic abnormalities in MPS I mice treated at birth with adeno-associated virus vector transducing the human alpha-L-iduronidase gene. Mol Ther 9(6):866–875. CrossRefPubMedGoogle Scholar
  43. 43.
    Osborn MJ, Webber BR, McElmurry RT, Rudser KD, DeFeo AP, Muradian M, Petryk A, Hallgrimsson B, Blazar BR, Tolar J, Braunlin EA (2017) Angiotensin receptor blockade mediated amelioration of mucopolysaccharidosis type I cardiac and craniofacial pathology. J Inherit Metab Dis 40(2):281–289. CrossRefPubMedGoogle Scholar
  44. 44.
    Visigalli I, Delai S, Politi LS, Di Domenico C, Cerri F, Mrak E, D'Isa R, Ungaro D, Stok M, Sanvito F, Mariani E, Staszewsky L, Godi C, Russo I, Cecere F, Del Carro U, Rubinacci A, Brambilla R, Quattrini A, Di Natale P, Ponder K, Naldini L, Biffi A (2010) Gene therapy augments the efficacy of hematopoietic cell transplantation and fully corrects mucopolysaccharidosis type I phenotype in the mouse model. Blood 116(24):5130–5139. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Till Koehne
    • 1
  • Anja Köhn
    • 2
  • Reinhard E. Friedrich
    • 3
  • Uwe Kordes
    • 4
  • Thorsten Schinke
    • 5
  • Nicole Muschol
    • 2
  • Bärbel Kahl-Nieke
    • 1
  1. 1.Department of OrthodonticsUniversity Medical Center Hamburg-EppendorfHamburgGermany
  2. 2.Department of PediatricsUniversity Medical Center Hamburg-EppendorfHamburgGermany
  3. 3.Department of Oral and Maxillofacial SurgeryUniversity Medical Center Hamburg-EppendorfHamburgGermany
  4. 4.Department of Pediatric Hematology and OncologyUniversity Medical Center Hamburg-EppendorfHamburgGermany
  5. 5.Department of Osteology and BiomechanicsUniversity Medical Center Hamburg-EppendorfHamburgGermany

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