Fragile X premutation carriers: characteristic MR imaging findings of adult male patients with progressive cerebellar and cognitive dysfunction

Abstract

Background and purpose: Our purpose was to characterize the findings of MR imaging of the brain of adult male fragile X premutation carriers with a recently identified disorder characterized by ataxia, tremor, rigidity, and cognitive dysfunction.

Methods: MR imaging studies of the brain of 17 male patients were characterized for signal intensity and for size of ventricles, cerebral and cerebellar sulci, and brain stem. Comparison was made with age- and sex-matched control participants. Southern blot and/or polymerase chain reaction methods were used to analyze CGG trinucleotide repeats in the fragile X mental retardation 1 gene.

Results: Fifteen of 17 patients showed symmetrically decreased T1 and increased T2 signal intensity in cerebellar white matter lateral, superior, and inferior to the dentate nuclei. Fourteen of 17 had similar signal intensity alterations in the middle cerebellar peduncles. Cerebellar cortical atrophy was present in 16 of 17 and cerebral atrophy in 17 of 17. Evan's Index as a measure of ventricular size averaged 0.35 (range, 0.25-0.46), with that for age-matched control participants averaging 0.28 (range, 0.24-0.31) (P <.005). The mean third ventricle width was 11 mm (for control participants, 6 mm; P <.01). Corpus callosum was thinned in 14 of 16 participants. Middle cerebellar peduncles were atrophic when compared with those of control participants (P <.005). Pontine transverse dimension was 25 mm (for control participants, 31 mm; P <.005), and rostral-caudal length averaged 26 mm (for control participants, 29 mm; P <.005). CGG repeats clustered in the low to mid premutation range (86 +/- 10 CGG repeats) in the 17 patients.

Conclusion: MR imaging findings in symptomatic male fragile X premutation carriers are characteristic of this disorder. Recognition of these alterations may support a specific diagnosis and may have implications for the potential occurrence of fragile X syndrome in the children of reproductive age female relatives.

Fig 1.

Images from the case of a 66-year-old man with fragile X premutation. A–C, Axial view T2-weighted images show high signal intensity in white matter inferior and lateral to the deep cerebellar nuclei. Only slightly increased signal intensity can be seen in the MCPs. D, Coronal view T1-weighted contrast-enhanced image shows white matter regions of low signal intensity that do not show enhancement.

Fig 2.

Images from the case of a 70-year-old man with fragile X premutation. A and B, Axial view T2-weighted images show symmetrically increased T2 signal intensity in the cerebellum with mildly increased signal intensity in the MCPs. C, Coronal view T2-weighted image. Moderate cerebellar volume loss and severe parietal cortical volume loss can be seen with thinning of the corpus callosum. Punctate areas of cerebral white matter increased signal intensity. D, Sagittal view T1-weighted image shows mild pontine volume loss, decreased anteroposterior dimension of the pons, prominence in prepontine cistern, and severe thinning of the corpus callosum.

Fig 3.

Images from the case of a 61-year-old man with fragile X premutation. A and B, Increased signal intensity is shown in inferior cerebellar white matter on inversion recovery images. The deep cerebellar nuclei are normal in size and signal intensity. The pons is normal in signal intensity. C and D, Axial view T1-weighted images show volume loss involving the pontomesencephalic junction with enlargement of the temporal horns and ambient cisterns. The cerebral peduncles are moderately decreased in area (D). Moderate enlargement of the lateral ventricles and cerebral sulci can be seen. E, Axial view inversion recovery image shows increased signal intensity in the thinned corpus callosum and in periventricular white matter.

Fig 4.

Images from the case of a 69-year-old man with fragile X premutation. A and B, Axial view T2-weighted images show increased signal intensity in the MCPs, which are slightly thinned in the oblique transverse dimension. Prominence in size of the subarachnoid spaces can be seen. The pons shows a nonspecific right paramedian punctate area of increased signal intensity. C, Axial view T2-weighted image. Mesencephalon and middle cerebral peduncles are mildly decreased in size, with prominence of the ambient cisterns. D, Axial view inversion recovery image shows volume loss with increased signal intensity in frontal and parietal white matter and in the genu of the thinned corpus callosum. E, Coronal view T2-weighted image shows volume loss and increased T2 signal intensity in the frontal white matter and in the thinned corpus callosum.