Clinical epidemiologic characterization of orthopaedic and neurological manifestations in children with leukodystrophies.

BACKGROUND: Leukodystrophies (LKDs) are spectra of clinical conditions characterized primarily by brain white matter abnormalities. Although this condition was previously defined around inherited disorders of the white matter of the brain, current application includes acquired and sporadic conditions and some rare conditions that affect gray matter. Over the past 2 decades, information had become available on the clinical subtypes due to neurodiagnostic imaging and improvement in the genetic studies (cytogenetics and molecular genetics) of LKD. However, the epidemiologic profile of LKD remains largely unknown. We aimed in this study to characterize LKD by demographics, family history, orthopaedic and neurological manifestations, and clinical subtypes.
METHODS: Trained medical personnel reviewed medical records of the study population diagnosed with LKD from 1986 to 2008. Using a retrospective review design, we determined the prevalence of the different clinical subtypes of LKD, family history, orthopaedic and neurological manifestations, and the demographics in LKD. The frequency and percentage (proportion, standard error, and 95% confidence interval for proportion) and the χ statistic and Fisher exact test for comparison of clinical subtypes were the statistical techniques used in the data analysis.
RESULTS: Forty-four children were diagnosed with LKD between 1986 and 2008, of whom 25.0% had metachromatic LKD and 20.5% had Pelizaeus-Merzbacher LKD, whereas 40.9% were unspecified LKD. LKDs were more common among boys (63.6%), Whites (77.3%), and more likely to be diagnosed at age <3 years. Scoliosis (70.4%), hamstring contractures (81.8%), acquired hip dysplasia (88.6%), and equinus foot deformity (75.0%) were the most common orthopaedic manifestations. Common neurological manifestations were seizures (45.4%) and spasticity (77.3%). There was a statistically significant difference in sex and family history, seizures, hip dislocation, and hip subluxation, with respect to the clinical subtype of LKD, P<0.05.
CONCLUSIONS: This epidemiologic characterization of LKD validates basic and clinical data on the familial history of LKD and its higher prevalence among boys. The orthopaedic manifestations common in LKD are scoliosis, hamstring contractures, acquired hip dysplasia, and equinus foot deformity, whereas common neurological manifestations are seizures and spasticity. These data are indicative of the need for orthopaedic surgeons to take into consideration this clinical epidemiologic aspect of LKD in the evaluation, treatment planning, and clinical expectations for these patients.