The Association of Scoliosis and NSD1 Gene Deletion in Sotos Syndrome Patients.
Journal
Spine
ISSN: 1528-1159
Titre abrégé: Spine (Phila Pa 1976)
Pays: United States
ID NLM: 7610646
Informations de publication
Date de publication:
01 Jul 2021
01 Jul 2021
Historique:
pubmed:
18
12
2020
medline:
10
7
2021
entrez:
17
12
2020
Statut:
ppublish
Résumé
A retrospective comparative study. The aim of this study was to examine the NSD1 abnormalities in patients diagnosed with Sotos syndrome and its correlation with the presence, severity, and progression of associated scoliosis. Scoliosis has been reported in approximately 30% of patients diagnosed with Sotos syndrome, a genetic disorder characterized by a distinctive facial appearance, learning disability, and overgrowth. Sotos syndrome is mainly attributed to NSD1 haploinsufficiency, but with ethnical differences in genetic profile: NSD1 microdeletions are frequently identified in Japanese Sotos patients whereas intragenic mutations are more frequently found in non-Japanese patients. Although possible genotype-phenotype correlations have been proposed, the genotype of Sotos syndrome patients suffering from scoliosis has not been examined. The medical records and spinal radiographs of 63 consecutive Sotos syndrome patients at a single center were reviewed. Fluorescent in situ hybridization or microarray comparative genomic hybridization and DNA sequencing or multiplex ligation-dependent probe amplification were performed to detect 5q35 microdeletion involving the NSD1 gene and intragenic mutations of the NSD1 gene, respectively. The phenotypes of all cases and radiological assessments for the presence and progression of scoliosis were studied. NSD1 abnormalities were identified in 55 patients (87%): microdeletion in 34 patients (54%) and intragenic mutation in 22 patients (33%). Scoliosis was observed in 26 patients (41%), with a significantly higher ratio of microdeletions than mutations. The 10 patients with progressive scoliosis all had NSD1 microdeletions. Scoliosis was a common phenotypical trait in children with Sotos syndrome and its presence as well as progression were higher in cases with NSD1 microdeletions. Although all Sotos syndrome patients should be monitored for scoliosis, clinicians should be made aware that patients with NSD1 microdeletions have a higher probability of scoliosis development and progression that may require early intervention.Level of Evidence: 3.
Sections du résumé
STUDY DESIGN
METHODS
A retrospective comparative study.
OBJECTIVE
OBJECTIVE
The aim of this study was to examine the NSD1 abnormalities in patients diagnosed with Sotos syndrome and its correlation with the presence, severity, and progression of associated scoliosis.
SUMMARY OF BACKGROUND DATA
BACKGROUND
Scoliosis has been reported in approximately 30% of patients diagnosed with Sotos syndrome, a genetic disorder characterized by a distinctive facial appearance, learning disability, and overgrowth. Sotos syndrome is mainly attributed to NSD1 haploinsufficiency, but with ethnical differences in genetic profile: NSD1 microdeletions are frequently identified in Japanese Sotos patients whereas intragenic mutations are more frequently found in non-Japanese patients. Although possible genotype-phenotype correlations have been proposed, the genotype of Sotos syndrome patients suffering from scoliosis has not been examined.
METHODS
METHODS
The medical records and spinal radiographs of 63 consecutive Sotos syndrome patients at a single center were reviewed. Fluorescent in situ hybridization or microarray comparative genomic hybridization and DNA sequencing or multiplex ligation-dependent probe amplification were performed to detect 5q35 microdeletion involving the NSD1 gene and intragenic mutations of the NSD1 gene, respectively. The phenotypes of all cases and radiological assessments for the presence and progression of scoliosis were studied.
RESULTS
RESULTS
NSD1 abnormalities were identified in 55 patients (87%): microdeletion in 34 patients (54%) and intragenic mutation in 22 patients (33%). Scoliosis was observed in 26 patients (41%), with a significantly higher ratio of microdeletions than mutations. The 10 patients with progressive scoliosis all had NSD1 microdeletions.
CONCLUSION
CONCLUSIONS
Scoliosis was a common phenotypical trait in children with Sotos syndrome and its presence as well as progression were higher in cases with NSD1 microdeletions. Although all Sotos syndrome patients should be monitored for scoliosis, clinicians should be made aware that patients with NSD1 microdeletions have a higher probability of scoliosis development and progression that may require early intervention.Level of Evidence: 3.
Identifiants
pubmed: 33332788
doi: 10.1097/BRS.0000000000003879
pii: 00007632-202107010-00007
doi:
Substances chimiques
Histone-Lysine N-Methyltransferase
EC 2.1.1.43
NSD1 protein, human
EC 2.1.1.43
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
E726-E733Informations de copyright
Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.
Références
Tatton-Brown K, Douglas J, Coleman K, et al. Genotype-phenotype associations in Sotos syndrome: an analysis of 266 individuals with NSD1 aberrations. Am J Hum Genet 2005; 77:193–204.
Türkmen S, Gillessen-Kaesbach G, Meinecke P, et al. Mutations in NSD1 are responsible for Sotos syndrome, but are not a frequent finding in other overgrowth phenotypes. Eur J Hum Genet 2003; 11:858–865.
Kurotaki N, Imaizumi K, Harada N, et al. Haploinsufficiency of NSD1 causes Sotos syndrome. Nat Genet 2002; 30:365–366.
Nagai T, Matsumoto N, Kurotaki N, et al. Sotos syndrome and haploinsufficiency of NSD1: clinical features of intragenic mutations and submicroscopic deletions. J Med Genet 2003; 40:285–289.
Tatton-Brown K, Douglas J, Coleman K, et al. Multiple mechanisms are implicated in the generation of 5q35 microdeletions in Sotos syndrome. J Med Genet 2005; 42:307–313.
Visser R, Hasegawa T, Niikawa N, et al. Analysis of the NSD1 promoter region in patients with a Sotos syndrome phenotype. J Hum Genet 2006; 51:15–20.
Douglas J, Hanks S, Temple IK, et al. NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes. Am J Hum Genet 2003; 72:132–143.
Rio M, Clech L, Amiel J, et al. Spectrum of NSD1 mutations in Sotos and Weaver syndromes. J Med Genet 2003; 40:436–440.
de Boer L, Kant SG, Karperien M, et al. Genotype-phenotype correlation in patients suspected of having Sotos syndrome. Horm Res 2004; 62:197–207.
Cecconi M, Forzano F, Milani D, et al. Mutation analysis of the NSD1 gene in a group of 59 patients with congenital overgrowth. Am J Med Genet A 2005; 134:247–253.
Tatton-Brown K, Rahman N. Sotos syndrome. Eur J Hum Genet 2007; 15:264–271.
Sweeney E, Fryer A, Donnai D. Sotos syndrome: two cases with severe scoliosis. Clin Dysmorphol 2002; 11:121–124.
Haga N, Nakamura S, Shimode M, et al. Scoliosis in cerebral gigantism, Sotos syndrome. A case report Spine (Phila Pa 1976) 1996; 21:1699–1702.
Tsirikos AI, Demosthenous N, McMaster MJ. Spinal deformity in patients with Sotos syndrome (cerebral gigantism). J Spinal Disord Tech 2009; 22:149–153.
Corrado R, Wilson AF, Tello C, et al. Sotos syndrome and scoliosis surgical treatment: a 10-year follow-up. Eur Spine J 2011; 20: (suppl 2): S271–S277.
Sotos JF, Dodge PR, Muirhead D, et al. Cerebral gigantism in childhood. A syndrome of excessively rapid growth and acromegalic features and a nonprogressive neurologic disorder. N Engl J Med 1964; 271:109–116.
Cole TR, Hughes HE. Sotos syndrome: a study of the diagnostic criteria and natural history. J Med Genet 1994; 31:20–32.
Imaizumi K, Kimura J, Matsuo M, et al. Sotos syndrome associated with a de novo balanced reciprocal translocation t(5;8)(q35;q24.1). Am J Med Genet 2002; 107:58–60.
Tatton-Brown K, Rahman N. Clinical features of NSD1-positive Sotos syndrome. Clin Dysmorphol 2004; 13:199–204.