Background: 22q11.2 deletion syndrome (22q11.2DS) is caused by recurrent, chromosome specific, low copy repeat mediated copy number losses of chromosome 22q11. The Children’s Hospital of Philadelphia has been involved in the clinical care of individuals with what is now known as 22q11.2DS since our initial report of the association with DiGeorge syndrome in 1982. Methods: We reviewed the medical records on our continuously growing longitudinal cohort of 1,421 patients with molecularly confirmed 22q11.2DS from 1992 to 2018. Results: Most individuals are Caucasian and older than eight years old. The median age at diagnosis was 360 days. The majority of patients (85%) had typical LCR22A-LCR22D deletions, and only 7% of these typical deletions were inherited from a parent harboring the deletion constitutionally. However, 6% of individuals harbored other nested deletions that would not be identified by traditional 22q11.2 FISH, thus requiring an orthogonal technology to diagnose. Major medical problems included immune dysfunction or allergies (77%), palatal abnormalities (67%), congenital heart disease (64%), gastrointestinal difficulties (65%), endocrine dysfunction (>50%), scoliosis (50%), renal anomalies (16%), and airway abnormalities. Median full-scale IQ was 76, with no significant difference between individuals with and without congenital heart disease or hypocalcemia. Characteristic dysmorphic facial features were present in most, but dermatoglyphic patterns of our cohort are similar to normal controls. Conclusions: This is the largest longitudinal study of patients with 22q11.2DS, helping to further describe the condition and aid in diagnosis and management. Further surveillance will likely elucidate additional clinically relevant findings as they age.

Schizophrenia occurs in about one in four individuals with 22q11.2 deletion syndrome (22q11.2DS). The aim of this International Brain and Behavior 22q11.2DS Consortium (IBBC) study was to identify genetic factors that contribute to schizophrenia, in addition to the ~20-fold increased risk conveyed by the 22q11.2 deletion. Using whole-genome sequencing data from 519 unrelated individuals with 22q11.2DS, we conducted genome-wide comparisons of common and rare variants between those with schizophrenia and those with no psychotic disorder at age ≥25 years. Available microarray data enabled direct comparison of polygenic risk for schizophrenia between 22q11.2DS and independent population samples with no 22q11.2 deletion, with and without schizophrenia (total n=35,182). Polygenic risk for schizophrenia within 22q11.2DS was significantly greater for those with schizophrenia (p adj =6.73x10-6). Novel reciprocal case-control comparisons between the 22q11.2DS and population-based cohorts showed that polygenic risk score was significantly greater in individuals with psychotic illness, regardless of the presence of the 22q11.2 deletion. Within the 22q11.2DS cohort, results of gene-set analyses showed some support for rare variants affecting synaptic genes. No common or rare variants within the 22q11.2 deletion region were significantly associated with schizophrenia. These findings suggest that in addition to conferring a greatly increased risk to schizophrenia, the risk is higher when the 22q11.2 deletion and common polygenic risk factors that contribute to schizophrenia in the general population are both present.

Study Design. Retrospective cohort study. Objective. The present study is the first to assess the impact of paraspinal sarcopenia on patient-reported outcome measures (PROMs) following posterior cervical decompression and fusion (PCDF). Summary of Background Data. While the impact of sarcopenia on PROMs following lumbar spine surgery is well-established, the impact of sarcopenia on PROMs following PCDF has not been investigated. Materials and Methods. We performed a retrospective review of patients undergoing PCDF from C2 to T2 at a single institution between the years 2017 and 2020. Two independent reviewers who were blinded to the clinical outcome scores utilized axial cuts of T2-weighted magnetic resonance imaging sequences to assess fatty infiltration of the bilateral multifidus muscles at the C5–C6 level and classify patients according to the Fuchs Modification of the Goutalier grading system. PROMs were then compared between subgroups. Results. We identified 99 patients for inclusion in this study, including 28 patients with mild sarcopenia, 45 patients with moderate sarcopenia, and 26 patients with severe sarcopenia. There was no difference in any preoperative PROM between the subgroups. Mean postoperative Neck Disability Index scores were lower in the mild and moderate sarcopenia subgroups (12.8 and 13.4, respectively) than in the severe sarcopenia subgroup (21.0, P<0.001). A higher percentage of patients with severe multifidus sarcopenia reported postoperative worsening of their Neck Disability Index (10 patients, 38.5%; P=0.003), Visual Analog Scale Neck scores (7 patients, 26.9%; P=0.02), Patient-Reported Outcome Measurement Information System Physical Component Scores (10 patients, 38.5%; P=0.02), and Patient-Reported Outcome Measurement Information System Mental Component Scores (14 patients, 53.8%; P=0.02). Conclusion. Patients with more severe paraspinal sarcopenia demonstrate less improvement in neck disability and physical function postoperatively and are substantially more likely to report worsening PROMs postoperatively. Level of Evidence. 3.

Study Design: This was a retrospective cohort study. Objective: The present study is the first to investigate whether cervical paraspinal sarcopenia is associated with cervicothoracic sagittal alignment parameters after posterior cervical fusion (PCF). Summary of Background Data: Few studies have investigated the association between sarcopenia and postoperative outcomes after cervical spine surgery. Methods: We retrospectively reviewed patients undergoing PCF from C2–T2 at a single institution between the years 2017–2020. Two independent reviewers utilized axial cuts of T2-weighted magnetic resonance imaging sequences to perform Goutallier classification of the bilateral semispinalis cervicis (SSC) muscles. Cervical sagittal alignment parameters were compared between subgroups based upon severity of SSC sarcopenia. Results: We identified 61 patients for inclusion in this study, including 19 patients with mild SSC sarcopenia and 42 patients with moderate or severe SSC sarcopenia. The moderate-severe sarcopenia subgroup demonstrated a significantly larger change in C2–C7 sagittal vertical axis (+6.8 mm) from the 3-month to 1-year postoperative follow-up in comparison to the mild sarcopenia subgroup (−2.0 mm; P=0.02). The subgroup of patients with moderate-severe sarcopenia also demonstrated an increase in T1–T4 kyphosis (10.9–14.2, P=0.007), T1 slope (28.2–32.4, P=0.003), and C2 slope (24.1–27.3, P=0.05) from 3-month to 1-year postoperatively and a significant decrease in C1-occiput distance (6.3–4.1, P=0.002) during this same interval. Conclusions: In a uniform cohort of patients undergoing PCF from C2–T2, SSC sarcopenia was associated with worsening cervicothoracic alignment from 3-month to 1-year postoperatively.