Musculoskeletal phenotypes in 3q29 deletion syndrome

3q29 deletion syndrome (3q29del) is a rare genomic disorder caused by a 1.6 Mb deletion (hg19, chr3:195725000–197350000). 3q29del is associated with neurodevelopmental and psychiatric phenotypes, including an astonishing >40-fold increased risk for schizophrenia, but medical phenotypes are less well-described. We used the online 3q29 registry ([3q29deletion.org][1]) to recruit 57 individuals with 3q29del (56.14% male) and requested information about musculoskeletal phenotypes with a custom questionnaire. 85.96% of participants with 3q29del reported at least one musculoskeletal phenotype. Congenital anomalies were most common (70.18%), with pes planus (40.35%), pectus excavatum (22.81%), and pectus carinatum (5.26%) significantly elevated relative to the pediatric general population. 49.12% of participants reported fatigue after 30 minutes or less of activity. Bone fractures (8.77%) were significantly elevated relative to the pediatric general population, suggesting 3q29del impacts bone strength. Participants commonly report receiving medical care for musculoskeletal complaints (71.93%), indicating that these phenotypes impact quality of life for individuals with 3q29del. This is the most comprehensive description of musculoskeletal phenotypes in 3q29del to date, suggests ideas for clinical evaluation, and expands our understanding of the phenotypic spectrum of this syndrome. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by NIH R01 MH110701 and NIH T32 GM0008490. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Institutional Review Board of Emory University gave ethical approval for this work. Institutional Review Board of Rutgers University gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. [1]: http://3q29deletion.org