An Unusual Pattern of Premature Cervical Spine Degeneration in STAT3-LOF

• Published in: Journal of clinical immunology Vol. 41; no. 3; pp. 576 - 584
• Main Authors: Mitchell, Amelia L., Urban, Amanda K., Freeman, Alexandra F., Hammoud, Dima A.
• Format: Journal Article
• Language: English
• Published: New York Springer US 01-04-2021; Springer Nature B.V
• Subjects: Adolescent; Adult; Age; Biomedical and Life Sciences; Biomedicine; Bone Density; Bone mineral density; Cervical Vertebrae - pathology; Compression; Degeneration; Female; Fractures; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Immunoglobulin E; Immunology; Infectious Diseases; Internal Medicine; Loss of Function Mutation - genetics; Magnetic Resonance Imaging; Male; Medical Microbiology; Middle Aged; Neurological diseases; Original Article; Osteoporosis; Scoliosis; Scoliosis - diagnosis; Scoliosis - etiology; Severity of Illness Index; Spinal cord; Spinal Diseases - diagnosis; Spinal Diseases - etiology; Spine (cervical); Spondylolisthesis; Stat3 protein; STAT3 Transcription Factor - genetics; Trauma; Young Adult; Magnetic resonance imaging; STAT3-LOF; Cervical spine degeneration; Primary immunodeficiency
• ISSN: 0271-9142; 1573-2592
• DOI: 10.1007/s10875-020-00926-z

Loss of function mutations in
STAT3
(STAT3-LOF; autosomal dominant hyper-IgE (Job’s) syndrome) are associated with a variety of musculoskeletal manifestations, including scoliosis, osteoporosis, and minimal trauma fractures. This retrospective magnetic resonance (MR) imaging study sought to characterize an unusual pattern of cervical spine degeneration among a cohort of STAT3-LOF patients. Cervical spine MR images of the STAT3-LOF cohort (
n
 = 38) were assessed for a variety of degenerative changes and compared to age-matched groups of controls (
n
 = 42) without known immune or musculoskeletal abnormalities. A unique pattern of premature cervical spine degeneration was identified among the STAT3-LOF cohort which included straightening and eventual reversal of the normal cervical lordosis, mainly due to multi-level spondylolisthesis, as well as early development of spinal canal narrowing, cord compression, and myelomalacia. Cervical spine degeneration in the STAT3-LOF cohort was significantly worse than controls in both the 30–45 and 45 + age groups. Moderate to severe degenerative changes were present after age 30, and markedly worsened over time in several cases. Bone mineral density (BMD) had a moderate negative correlation with cervical degeneration severity and a strong negative correlation with age among STAT3-LOF participants. Cervical degeneration in STAT3-LOF appears to be progressive and could result in cord compromise if left unaddressed. Focused history and physical examination for signs of neurologic compromise as well as periodic MR imaging are thus recommended for the evaluation of premature cervical spine degeneration in STAT3-LOF patients after age 30 so that timely surgical interventions may be considered to prevent spinal cord damage and permanent neurological deficits.