Orthopaedic manifestations within the 22q11.2 Deletion syndrome: A systematic review

Abstract

The 22q11.2 Deletion Syndrome (22q11.2DS) is the most common microdeletion syndrome with an estimated prevalence of 1:4,000 live births. 22q11.2DS is known to have wide phenotypic variability, including orthopaedic manifestations. The purpose of this systematic review is to increase the awareness of orthopaedic manifestations associated with 22q11.2DS. This systematic review was performed according to the PRISMA Guidelines. Original epidemiological studies on the prevalence of orthopaedic manifestations within 22q11.2DS were systematically searched for in PubMed and EMBASE. The included articles were scored according to a risk-of-bias tool, a best-evidence synthesis was performed and the prevalence data was extracted. Sixty-nine published manuscripts described 58 orthopaedic manifestations in a total of 6,055 patients. The prevalence of at least one cervical or occipital anomaly is 90.5-100% (strong evidence). Fourteen studies (n = 2,264) revealed moderate evidence for a wide scoliosis prevalence of 0.6-60%. Two studies demonstrated that 5-6.4% of all 22q11.2DS patients required surgical scoliosis correction. Fifteen studies (n = 2,115) reported a 1.1-13.3% prevalence of clubfoot with moderate evidence. Other reported orthopaedic manifestations are patellar dislocation (10-20%), juvenile rheumatic arthritis (3.75%), impaired growth and skeletal anomalies like polydactyly (1.0-3.7%), syndactyly (11-11.8%), butterfly vertebrae (11.1%) and 13 ribs (2-19%). Orthopaedic findings are important manifestations of the 22q11.2DS, both in bringing patients to diagnostic attention and in requiring surveillance and appropriate intervention. Data on these manifestations are scattered and incomprehensive. Routinely screening for cervical anomalies, scoliosis, and upper and lower limb malformations is recommended in this vulnerable group of patients.

What is new with 22q? An update from the 22q and You Center at the Children's Hospital of Philadelphia

“…Cervical spine anomalies were noted in 46% of individuals, which is substantially lower than previous estimates, suggesting ascertainment bias due to a smaller number of patients being evaluated by Orthopedics (Homans et al, 2017). Additional skeletal abnormalities included vertebral anomalies, talipes equinovarus, polydactyly, camptodactyly, patellar dislocation, hammer toe (Ming et al, 1997; Homans et al, 2017). These findings underscore the importance of evaluation by an orthopedic surgeon.…”

22q11.2 Deletion Syndrome as a Human Model for Idiopathic Scoliosis

“…This was because in the general population, and most likely also in 22q11.2DS, the pathoetiology of congenital scoliosis varies greatly from the development of idiopathic scoliosis [ 22 ]. It is known that in 22q11.2DS, the rate of congenital spinal malformations, especially in the cervical spine, is higher than the general population; therefore, if 22q11.2DS scoliosis were to be used as a ‘model’ to study idiopathic scoliosis, the congenital curves should be excluded [ 34 ]. Third, 22q11.2DS is a multisystem syndrome with many phenotypes resulting, for example, in hypocalcemia and a lower bone mineral density in half of the patients [ 14 , 35 ].…”

Cervical Spine Malformations Associated With a 5q34-5q35.2 Micro-interstitial Deletion: A Case Report

“…The prevalence of developmental cervical variation in 22q11.2 deletion syndrome is nearly 100%, in addition to scoliosis and limb malformations. Therefore, evaluations for screening of various skeletal anomalies are recommended in this genetic disorder [10].…”