Evidence of an inherited predisposition for cervical spondylotic myelopathy.
METHODS
A retrospective, population-based study cross-referencing a genealogic database of over 2 million Utah residents with 10 years of clinical diagnosis data from a large tertiary hospital.


OBJECTIVE
The objective of this study is to determine the presence or absence of an inherited predisposition to the development of cervical spondylotic myelopathy (CSM).


BACKGROUND
A genetic predisposition for the development of cervical spondylosis has been discussed in the literature with low-quality evidence. Families with a high incidence of disease or early-onset disease in monozygotic twins have both been reported. However, these suggestions of an inherited predisposition for disease have never been rigorously studied. The purpose of this study is to determine a genetic predisposition among patients diagnosed with CSM.


METHODS
The Utah Population Database combines health and genealogic data on over 2 million Utah residents. International Classification of Diseases, Ninth Revision (ICD-9) codes were used to identify 486 patients in the database with a diagnosis of CSM (ICD-9 code 721.1). The hypothesis of excessive familial clustering was tested using the Genealogical Index of Familiality (GIF), and relative risks (RRs) in relatives were estimated by comparing rates of disease in relatives with rates estimated in the relatives of five matched controls for each case. This methodology has been previously reported and validated for other disease conditions but not for CSM.


RESULTS
The GIF analysis for patients with CSM showed significant excess relatedness for disease (P < 0.001). RRs were significantly elevated in both first- (RR = 5.21, CI = 2.1-13.2, P < 0.001) and third-degree relatives (RR = 1.95, CI = 1.04-3.7, P < 0.05).


CONCLUSIONS
Excess relatedness of cases and significantly elevated RRs to both close and distant relatives supports an inherited predisposition to CSM.
Department of Orthopaedics, University of Utah School of Medicine, Salt Lake City, UT, USA. alpesh.patel@hsc.utah.edu
Alpesh A
AA
Patel
William Ryan
WR
Spiker
Michael
M
Daubs
Darrel S
DS
Brodke
Lisa A
LA
Cannon-Albright
D002574:Cervical Vertebrae; D016000:Cluster Analysis; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D012189:Retrospective Studies; D012306:Risk; D013117:Spinal Cord Compression / Q000175:diagnosis / Q000209:etiology / Q000235:genetics*; D055009:Spondylosis / Q000150:complications / Q000175:diagnosis / Q000235:genetics*
Arthritis Rheum. 1999 Feb;42(2):366-72
10025932
Am J Respir Crit Care Med. 2007 Nov 1;176(9):865-70
17690335
J Neurosurg Spine. 2007 Apr;6(4):344-9
17436924
Stat Med. 2005 Mar 15;24(5):729-40
15696504
Br J Radiol. 1969 Jan;42(493):9-16
5782795
Int J Cancer. 2005 Nov 20;117(4):655-61
15929077
Clin Orthop Relat Res. 1989 Feb;(239):69-93
2536306
J Bone Joint Surg Am. 2009 May;91(5):1136-42
19411462
J Infect Dis. 2008 Jan 1;197(1):18-24
18171280
Spine (Phila Pa 1976). 1998 Dec 15;23(24):2730-7
9879098
J Neurosurg. 1998 Jul;89(1):139-41
9647185
Skeletal Radiol. 1984;11(3):178-82
6538995
Am J Hum Genet. 1984 Jul;36(4):836-57
6591796
Science. 1994 Oct 7;266(5182):66-71
7545954
Spine J. 2006 Nov-Dec;6(6 Suppl):190S-197S
17097538