Skeletal and Cranial Growth Among Children with Achondroplasia

Achondroplasia, the most common form of disproportionate short stature, is caused by a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. Affected children may experience severely impaired foramen magnum growth during the first years of life, which may necessitate neurosurgical intervention. The skeletal abnormalities seen in achondroplasia can result in respiratory and neurologic comorbidities, including cord compression at the cervicomedullary junction, ventriculomegaly, hydrocephalus, and sleep apnea. These result in part from foramen magnum narrowing. 7 Internal There is a critical need to identify natural and modified history of foramen magnum growth in normal children and children with achondroplasia in order to develop predictive imaging biomarkers of spinal cord compression. 1 There are no normative data for foramen magnum growth and shape. Such biomarkers could be used for early diagnosis of spinal cord compression, monitoring of disease progression, assessment of candidacy for therapy, and evaluation of treatment response. 2 There are limited data on the morphometry of the craniocervical junction using cross-sectional imaging with CT and MRI of patients with achondroplasia. Existing data in the literature was derived from small single institutional studies. 3 Interventions to mitigate the risk of foramen magnum stenosis are needed. A necessary first step, however, is to tandemly assess the linear and cranial growth of children with and without achondroplasia. This type of data may enable the creation of endpoints in clinical trials that address bone growth in young children with achondroplasia. Understanding the range of foramen magnum cross-sectional area in a large cohort of children with achondroplasia as measured by recent head MRI or CT scans with newer technology is also of interest as much of the available and relevant data were published several decades ago and sample sizes were small.