Craniofacial growth and function in achondroplasia: a multimodal 3D study on 15 patients.
Achondroplasia
Cephalometrics
Craniofacial growth
FGFR3
Geometric morphometrics
Principal component analysis
Sleep apnoea
Journal
Orphanet journal of rare diseases
ISSN: 1750-1172
Titre abrégé: Orphanet J Rare Dis
Pays: England
ID NLM: 101266602
Informations de publication
Date de publication:
18 04 2023
18 04 2023
Historique:
received:
19
04
2022
accepted:
11
03
2023
medline:
20
4
2023
pubmed:
19
4
2023
entrez:
19
04
2023
Statut:
epublish
Résumé
Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome. A multimodal study was performed based on a paediatric cohort of 15 achondroplasia patients (mean age, 7.8 ± 3.3 years), including clinical and sleep study data, 2D cephalometrics, and 3D geometric morphometry analyses, based on CT-scans (mean age at CT-scan: patients, 4.9 ± 4.9 years; controls, 3.7 ± 4.2 years). Craniofacial phenotype was characterized by maxillo-zygomatic retrusion, deep nasal root, and prominent forehead. 2D cephalometric studies showed constant maxillo-mandibular retrusion, with excessive vertical dimensions of the lower third of the face, and modifications of cranial base angles. All patients with available CT-scan had premature fusion of skull base synchondroses. 3D morphometric analyses showed more severe craniofacial phenotypes associated with increasing patient age, predominantly regarding the midface-with increased maxillary retrusion in older patients-and the skull base-with closure of the spheno-occipital angle. At the mandibular level, both the corpus and ramus showed shape modifications with age, with shortened anteroposterior mandibular length, as well as ramus and condylar region lengths. We report a significant correlation between the severity of maxillo-mandibular retrusion and obstructive sleep apnea syndrome (p < 0.01). Our study shows more severe craniofacial phenotypes at older ages, with increased maxillomandibular retrusion, and demonstrates a significant anatomo-functional correlation between the severity of midface and mandible craniofacial features and obstructive sleep apnea syndrome.
Sections du résumé
BACKGROUND
Achondroplasia is the most frequent FGFR3-related chondrodysplasia, leading to rhizomelic dwarfism, craniofacial anomalies, stenosis of the foramen magnum, and sleep apnea. Craniofacial growth and its correlation with obstructive sleep apnea syndrome has not been assessed in achondroplasia. In this study, we provide a multimodal analysis of craniofacial growth and anatomo-functional correlations between craniofacial features and the severity of obstructive sleep apnea syndrome.
METHODS
A multimodal study was performed based on a paediatric cohort of 15 achondroplasia patients (mean age, 7.8 ± 3.3 years), including clinical and sleep study data, 2D cephalometrics, and 3D geometric morphometry analyses, based on CT-scans (mean age at CT-scan: patients, 4.9 ± 4.9 years; controls, 3.7 ± 4.2 years).
RESULTS
Craniofacial phenotype was characterized by maxillo-zygomatic retrusion, deep nasal root, and prominent forehead. 2D cephalometric studies showed constant maxillo-mandibular retrusion, with excessive vertical dimensions of the lower third of the face, and modifications of cranial base angles. All patients with available CT-scan had premature fusion of skull base synchondroses. 3D morphometric analyses showed more severe craniofacial phenotypes associated with increasing patient age, predominantly regarding the midface-with increased maxillary retrusion in older patients-and the skull base-with closure of the spheno-occipital angle. At the mandibular level, both the corpus and ramus showed shape modifications with age, with shortened anteroposterior mandibular length, as well as ramus and condylar region lengths. We report a significant correlation between the severity of maxillo-mandibular retrusion and obstructive sleep apnea syndrome (p < 0.01).
CONCLUSIONS
Our study shows more severe craniofacial phenotypes at older ages, with increased maxillomandibular retrusion, and demonstrates a significant anatomo-functional correlation between the severity of midface and mandible craniofacial features and obstructive sleep apnea syndrome.
Identifiants
pubmed: 37072824
doi: 10.1186/s13023-023-02664-y
pii: 10.1186/s13023-023-02664-y
pmc: PMC10114380
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
88Informations de copyright
© 2023. The Author(s).
Références
Am J Med Genet A. 2012 Aug;158A(8):1987-93
pubmed: 22711495
Hum Mol Genet. 2014 Jun 1;23(11):2914-25
pubmed: 24419316
Nature. 1994 Sep 15;371(6494):252-4
pubmed: 8078586
Chest. 2004 Mar;125(3):872-8
pubmed: 15006944
Indian J Pathol Microbiol. 2021 Oct-Dec;64(4):776-779
pubmed: 34673602
Hum Mol Genet. 2016 Jul 15;25(14):2997-3010
pubmed: 27260401
Oral Surg Oral Med Oral Pathol. 1981 Sep;52(3):226-38
pubmed: 6945527
World Neurosurg. 2018 Jan;109:e460-e467
pubmed: 29024761
Bone. 2004 Jan;34(1):26-36
pubmed: 14751560
J Dent Res. 2016 Oct;95(11):1221-9
pubmed: 27250655
Nat Genet. 1995 Jul;10(3):357-9
pubmed: 7670477
J Clin Invest. 2016 May 2;126(5):1871-84
pubmed: 27064282
Int J Pediatr Otorhinolaryngol. 2006 Mar;70(3):453-61
pubmed: 16406083
Lancet. 2007 Jul 14;370(9582):162-172
pubmed: 17630040
J Med Genet. 1996 Sep;33(9):749-52
pubmed: 8880574
Radiology. 1995 Sep;196(3):757-63
pubmed: 7644640
Eur J Orthod. 1997 Jun;19(3):289-311
pubmed: 9239959
Am J Med Genet A. 2017 Apr;173(4):868-878
pubmed: 28239978
Plast Reconstr Surg. 2014 Sep;134(3):504-510
pubmed: 25158708
Am J Med Genet A. 2012 Nov;158A(11):2797-806
pubmed: 22987770
Nat Genet. 1995 Dec;11(4):462-4
pubmed: 7493034
Hum Mol Genet. 2009 Jan 15;18(2):227-40
pubmed: 18923003
Neurology. 1995 Mar;45(3 Pt 1):519-24
pubmed: 7898709
Laryngoscope. 2021 Apr;131(4):E1349-E1356
pubmed: 32886384
Braz Dent J. 2002;13(2):129-32
pubmed: 12238804
J Oral Maxillofac Surg. 2014 Jun;72(6):1173-9
pubmed: 24480760
Hum Mol Genet. 2000 Jan 22;9(2):249-58
pubmed: 10607835
Am J Hum Genet. 1997 Mar;60(3):555-64
pubmed: 9042914
Best Pract Res Clin Rheumatol. 2008 Mar;22(1):3-18
pubmed: 18328977
Genes Dev. 2015 Jul 15;29(14):1463-86
pubmed: 26220993
Development. 2001 Oct;128(19):3867-76
pubmed: 11585811
J Craniofac Genet Dev Biol Suppl. 1985;1:139-65
pubmed: 3877092
Proc Natl Acad Sci U S A. 2004 Aug 24;101(34):12555-60
pubmed: 15316116
Sci China Life Sci. 2019 Oct;62(10):1375-1380
pubmed: 31463736
Plast Reconstr Surg. 2013 Dec;132(6):993e-1000e
pubmed: 24281646
Rev Endocr Metab Disord. 2002 Dec;3(4):381-5
pubmed: 12424440
Otolaryngol Head Neck Surg. 1999 Feb;120(2):248-54
pubmed: 9949360
Osteoarthritis Cartilage. 2022 Apr;30(4):535-544
pubmed: 34864168
Bone. 2020 Dec;141:115579
pubmed: 32795681
Front Pediatr. 2020 Jun 22;8:330
pubmed: 32656168
J Pediatr. 1987 Apr;110(4):522-30
pubmed: 3559799