Validation of the finding of hypertrophy of the clava in infantile neuroaxonal dystrophy/PLA2G6 by biometric analysis.

INTRODUCTION: Infantile neuroaxonal dystrophy (INAD), an autosomal recessive neurodegenerative disorder due to PLA2G6 mutation, is classified both as a PLA2G6-associated neurodegeneration (PLAN) disorder and as one of the neurodegeneration with brain iron accumulation (NBIA) disorders. Age of onset and clinical presentation in INAD is variable. Typically described imaging features of cerebellar atrophy, cerebellar cortex bright FLAIR signal, and globus pallidus iron deposition are variable or late findings. We characterize clinical and neuroimaging phenotypes in nine children with confirmed PLA2G6 mutations and show a useful imaging feature, clava hypertrophy, which may aid in earlier identification of patients. Measurements of the clava confirm actual enlargement, rather than apparent enlargement due to volume loss of the other brain stem structures. METHODS: A retrospective clinical and MRI review was performed. Brain stem measurements were performed and compared with age-matched controls. RESULTS: We identified nine patients, all with novel PLA2G6 gene mutations. MRI, available in eight, showed clava hypertrophy, regardless of age or the absence of other more typically described neuroimaging findings. Brain autopsy in our cohort confirmed prominent spheroid bodies in the clava nuclei. CONCLUSION: Clava hypertrophy is an important early imaging feature which may aid in indentification of children who would benefit from specific testing for PLA2G6 mutations.

Teratogenicity of angiotensin converting enzyme inhibitors or receptor blockers.

Studies of 1st trimester exposure to ACE inhibitors and angiotensin receptor blockers examining teratogenicity have shown conflicting results. We systematically reviewed the literature and performed a meta-analysis evaluating the risk of major malformations. For the meta-analysis, we included studies comparing 1st trimester exposure to no exposure, or to exposure to other antihypertensives. Additionally, we conducted a qualitative analysis of studies that did not meet the inclusion criteria for the meta-analysis. A significant risk ratio was found when the exposed group was compared with healthy controls but not when compared with other antihypertensives. The qualitative analysis did not demonstrate a specific pattern of major malformations. Our results suggest that 1st trimester exposure to ACE inhibitors and angiotensin receptor blockers is not associated with an elevated risk of major malformations compared with other antihypertensives. A 1st trimester exposure to antihypertensives in general may be associated with an elevated risk of major malformations.