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

Jeffrey Campbell Nemours Children’s Hospital, Thomas Jefferson University, Wilmington, Delaware;

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Janet M. Legare Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;

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Joseph Piatt Nemours Children’s Hospital, Thomas Jefferson University, Wilmington, Delaware;

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Ethan Gough Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland;

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Richard M. Pauli Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;

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S. Shahrukh Hashmi McGovern Medical School at University of Texas Health, Houston, Texas

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David F. Rodriguez-Buritica McGovern Medical School at University of Texas Health, Houston, Texas

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Peggy Modaff Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;

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Mary Ellen Little Nemours Children’s Hospital, Thomas Jefferson University, Wilmington, Delaware;

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Maria Elena Serna McGovern Medical School at University of Texas Health, Houston, Texas

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Cory J. Smid Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;

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Lorena Dujmusic Department of Pediatrics, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin;

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Jacqueline T. Hecht McGovern Medical School at University of Texas Health, Houston, Texas

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Julie E. Hoover-Fong Department of Genetic Medicine, Greenberg Center for Skeletal Dysplasias, Johns Hopkins University, Baltimore, Maryland; and

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Michael B. Bober Nemours Children’s Hospital, Thomas Jefferson University, Wilmington, Delaware;

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Publication Date:
15 Sep 2023
Page Range:
1–8
Volume/Issue:
Publish Before Print
DOI link:
https://doi.org/10.3171/2023.7.PEDS2354
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OBJECTIVE

The objective of this study was to describe the incidence and management of hydrocephalus in patients with achondroplasia over a 60-year period at four skeletal dysplasia centers.

METHODS

The Achondroplasia Natural History Study (CLARITY) is a registry for clinical data from achondroplasia patients receiving treatment at four skeletal dysplasia centers in the US from 1957 to 2017. Data were entered and stored in a REDCap database and included surgeries with indications and complications, medical diagnoses, and radiographic information.

RESULTS

A total of 1374 patients with achondroplasia were included in this study. Of these, 123 (9%) patients underwent treatment of hydrocephalus at a median age of 14.4 months. There was considerable variation in the percentage of patients treated for hydrocephalus by center and decade of birth, ranging from 0% to 28%, although in the most recent decade, all centers treated less than 6% of their patients, with an average of 2.9% across all centers. Undergoing a cervicomedullary decompression (CMD) was a strong predictor for treatment of hydrocephalus (OR 5.8, 95% CI 3.9–8.4), although that association has disappeared in those born since 2010 (OR 1.1, 95% CI 0.2–5.7). In patients born since 1990, treatment of hydrocephalus with endoscopic third ventriculostomy (ETV) has become more common; it was used as the first line of treatment in 38% of patients in the most recent decade. Kaplan-Meier analysis suggests that a single ETV will treat hydrocephalus in roughly half of these patients.

CONCLUSIONS

While many children with achondroplasia have features of hydrocephalus with enlarged intracranial CSF spaces and relative macrocephaly, treatment of hydrocephalus in achondroplasia patients has become relatively uncommon in the last 20 years. Historically, there was a significant association between symptomatic foramen magnum stenosis and treatment of hydrocephalus, although concurrent treatment of both has fallen out of favor with the recognition that CMD alone will treat hydrocephalus in some patients. Despite good experimental data demonstrating that hydrocephalus in achondroplasia is best understood as communicating in nature, ETV appears to be reasonably successful in certain patients and should be considered an option in selected patients.

ABBREVIATIONS

CLARITY = Achondroplasia Natural History Study; CMD = cervicomedullary decompression; ETV = endoscopic third ventriculostomy; JHU = Johns Hopkins University; REDCap = Research Electronic Data Capture; VP = ventriculoperitoneal.
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Contributor Notes

Correspondence Jeffrey Campbell: Nemours Children’s Hospital, Thomas Jefferson University, Wilmington, DE. jeffrey.campbell@nemours.org.

INCLUDE WHEN CITING Published online September 15, 2023; DOI: 10.3171/2023.7.PEDS2354.

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 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. Authors maintain ownership of the data unless further agreement is pursued. Dr. Legare reported grants from BioMarin (via a subaward from Johns Hopkins) during the conduct of the study; and speakers bureau for BioMarin, and PI for a clinical trial for Ascendis Pharma, outside the submitted work. Dr. Rodriguez-Buritica reported lecture fees from BioMarin outside the submitted work; and serves as a lecturer for BioMarin-sponsored lectures on education about achondroplasia, for which there is a conflict of interest plan for his participation in this activity. Dr. Hoover-Fong reported grants from BioMarin during the conduct of the study; consulting, research support, and advisory board for BioMarin, QED, and Innoskel; and consulting for Novo Nordisk, outside the submitted work. Dr. Bober reported grants from BioMarin (investigator-initiated project) during the conduct of the study; and personal fees from BioMarin, Ascendis, Therachon, QED, and Tyra, outside the submitted work.

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