Achondroplasia Natural History Study (CLARITY): 60-year experience in cervicomedullary decompression in achondroplasia from four skeletal dysplasia centers

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  • 1 Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;
  • | 2 Greenberg Center for Skeletal Dysplasias, McKusick-Nathans Department of Genetic Medicine, and
  • | 3 Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland;
  • | 4 McGovern Medical School at University of Texas Health, Houston, Texas;
  • | 5 A. I. duPont Hospital for Children, Thomas Jefferson University, Wilmington, Delaware; and
  • | 6 Children’s Wisconsin, Medical College of Wisconsin, Milwaukee, Wisconsin
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OBJECTIVE

The authors sought to determine the overall incidence of cervicomedullary decompression (CMD) in patients with achondroplasia and the characteristics associated with those surgeries across multiple institutions with experience caring for individuals with skeletal dysplasias.

METHODS

Data from CLARITY (Achondroplasia Natural History Study) for 1374 patients with achondroplasia from four skeletal dysplasia centers (A. I. duPont Hospital for Children, Johns Hopkins University, University of Texas Health, and University of Wisconsin School of Medicine and Public Health) followed from 1957 to 2017 were recorded in a Research Electronic Data Capture (REDCap) database. Data collected and analyzed included surgeries, indications, complications, ages at time of procedures, screening procedures, and medical diagnoses.

RESULTS

There were 314 CMD procedures in 281 patients (20.5% of the entire cohort). The median age of first CMD was 1.3 years in males and 1.1 years in females. Over time, there was a decrease in the median age of patients at first CMD. All patients born before 1980 who underwent CMD had the procedure after 5 years of age, whereas 98% of patients born after 2010 underwent CMD before 5 years of age. In addition, a greater proportion of patients born in more recent decades had documented neuroimaging and polysomnography (PSG) prior to CMD. Ventriculoperitoneal shunts (VPSs) were placed more frequently in patients undergoing CMD (23%) than in the entire cohort (8%). Patients who required either CMD or VPS were 7 times more likely to require both surgeries than patients who required neither surgery (OR 7.0, 95% CI 4.66–10.53; p < 0.0001). Overall, 10.3% of patients who underwent CMD required a subsequent CMD.

CONCLUSIONS

The prevalence of CMD in this large achondroplasia cohort was 20%, with more recently treated patients undergoing first CMD at younger ages than earlier patients. The use of neuroimaging and PSG screening modalities increased over time, suggesting that increased and better surveillance contributed to earlier identification and intervention in patients with cervicomedullary stenosis and its complications.

ABBREVIATIONS

AIDHC = A. I. duPont Hospital for Children; CLARITY = Achondroplasia Natural History Study; CMD = cervicomedullary decompression; JHU = Johns Hopkins University; PAC = Primary Achondroplasia Cohort; PSG = polysomnography; UTH = University of Texas Health; UW = University of Wisconsin; VPS = ventriculoperitoneal shunt.

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Contributor Notes

Correspondence Janet M. Legare: University of Wisconsin School of Medicine and Public Health, Madison, WI. jmlegare@pediatrics.wisc.edu.

INCLUDE WHEN CITING Published online June 4, 2021; DOI: 10.3171/2020.12.PEDS20715.

Disclosures This research was funded through a grant from BioMarin Pharmaceutical Inc., project ID AAB2897, contract ID 68873 v5, and The Greenberg Center for Skeletal Dysplasias in the McKusick-Nathans Institute of the Department of Genetic Medicine at Johns Hopkins University (agency reference no. 2002941785, MSN 188299). The BioMarin Pharmaceutical Inc. grant was to Dr. Hoover-Fong with subcontracts to participating institutions. The authors maintain ownership of the data unless further agreement is pursued. Dr. Hoover-Fong, Dr. Bober, Dr. Hecht, and Dr. Legare have participated in advisory boards sponsored by BioMarin pertaining to achondroplasia. Dr. Hoover-Fong and Dr. Bober have been consulted by BioMarin, Alexion, and Therachon for clinical issues related to achondroplasia and other genetic skeletal conditions. Dr. Bober also reports consulting for Pfizer and Ascendis and receiving support of non–study-related clinical or research effort overseen by the author from BioMarin, Pfizer, Ascendis, and QED. Dr. Hoover-Fong also reports receiving clinical or research support for the study described (includes equipment or material) from Pfizer. Dr. Legare has provided education for BioMarin internal teaching conferences and been consulted by QED Therapeutics for clinical issues related to achondroplasia. All activities were reviewed and approved by the authors’ respective institutions. The data presented in this paper do not pertain to the investigational pharmaceutical agent under development by BioMarin.

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