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

Abstract

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.

Ataxia and pancytopenia caused by a mutation in TINF2

“…Ataxia is not a manifestation of Shwachman-Diamond syndrome; however neurological abnormalities and mild MRI changes consistent of hypoplasia of the cerebellar vermis, mesencephalon, pons, and medulla and corpus callosum have been reported (Toiviainen-Salo et al 2008). The patients was also tested for RECQL4 mutations as pancytopenia and developmental delay have been reported in this spectrum of disorders, which are also characterized by early aging, skin abnormalities and sometimes dystrophic nails (Knoell et al 1999).…”

Congenital neutropenia: diagnosis, molecular bases and patient management

“…Neonatal forms have been described, with respiratory distress, narrow thorax, pancytopenia [61,62], and especially neurological involvement (mental retardation) [63], predominant gastrointestinal disorders (gluten intolerance), growth retardation in the second year of life, and predominant bone involvement suggestive of a constitutional bone disorder [64]. Depending on the presenting manifestations, differential diagnoses include Cystic fibrosis, Pearson's syndrome (characterized by cytologic abnormalities and especially mitochondrial respiratory chain defects), Fanconi anemia (distinguished by the constitutional karyotype) and gluten intolerance.…”

Clinical and Molecular Pathophysiology of Shwachman–Diamond Syndrome

“…36,37 In a recent study, Kerr and colleagues 10 reported on the neuropsychological function in 34 children with SDS, comparing them to 13 sibling controls as well as 20 patients with cystic fibrosis matched for age and gender. Patients with SDS ranged widely in their abilities compared with controls, from severely impaired to superior in some areas measured.…”