Shwachman-Diamond syndrome is associated with structural brain alterations on MRI

Shwachman-Diamond syndrome (SDS) is an autosomal recessive condition that results from mutations in the SBDS gene, at chromosome 7q11. Main features include exocrine pancreatic failure, neutropenia and skeletal dysplasia. This study investigated brain structures by magnetic resonance imaging (MRI) in patients with SDS. MRI of the brain was performed in nine patients (7 males, age range 7-37 years) with SDS and mutations in the SBDS gene and in 18 age- and gender-matched controls. MRI images were assessed visually, and volumetric analyses of the brain matter and structural midsagittal measurements were performed. Eight out of nine SBDS mutation-verified patients reported learning difficulties. Patients with SDS had smaller occipitofrontal head circumferences than the controls (Z-score -1.3 vs. +0.3, P = 0.021), and decreased global brain volume (1.74 L vs. 1.94 L, P = 0.019); both gray matter (P = 0.042) and white matter (P = 0.007) volumes were reduced. Patients with SDS had no macroscopic brain malformations, but they had significantly smaller age- and head size-adjusted areas of posterior fossa (P = 0.006), vermis (P = 0.002), corpus callosum (P = 0.020), and pons (P = 0.002), and significantly larger cerebrum-vermis ratio (P < 0.0001) than the healthy controls. SDS patients had structurally smaller posterior fossa and cerebellar vermis, corpus callosum, and brainstem than the healthy controls. The MRI findings may be related to the neuropsychological features described in SDS.