Brain MR Imaging Findings in Woodhouse-Sakati Syndrome

Abstract

Background and purpose: Woodhouse-Sakati syndrome is a rare autosomal recessive disorder characterized by hypogonadism, alopecia, diabetes mellitus, and progressive extrapyramidal signs. The disease is caused by biallelic pathogenic variants in the DCAF17 gene. The purpose of this study was to describe the spectrum of brain MR imaging abnormalities in Woodhouse-Sakati syndrome.

Materials and methods: We reviewed brain MR images of 26 patients with a clinical and genetic diagnosis of Woodhouse-Sakati syndrome (12 males, 14 females; age range, 16-45 years; mean age, 26.6 years). Follow-up studies were conducted for 6 patients.

Results: All patients had abnormal MR imaging findings. The most common abnormalities were a small pituitary gland (76.9%), pronounced basal ganglia iron deposition (73%), and white matter lesions in 69.2%. White matter lesions showed frontoparietal and periventricular predominance. All white matter lesions spared subcortical U-fibers and were nonenhanced. Prominent perivascular spaces (15.3%) and restricted diffusion in the splenium of the corpus callosum (7.6%) were less frequent findings. Follow-up studies showed expansion of white matter lesions with iron deposition further involving the red nucleus and substantia nigra. Older age was associated with a more severe degree of white matter lesions (P < .001).

Conclusions: Small pituitary gland, accentuated iron deposition in the globus pallidus, and nonenhancing frontoparietal/periventricular white matter lesions were the most noted abnormalities seen in our cohort. The pattern and extent of these findings were observed to correlate with older age, reflecting a possible progressive myelin destruction and/or axonal loss. The presence of pituitary hypoplasia and white matter lesions can further distinguish Woodhouse-Sakati syndrome from other neurodegenerative diseases with brain iron accumulation subtypes.

Fig 1.

Sagittal T1-weighted MR imaging for patient 22 shows a partially empty sella and a small pituitary gland (arrow).

Fig 2.

Axial T2-weighted (A), FLAIR (B), and T2* (C) MR images in case 11 show putaminal blooming artifacts (arrows) reflecting iron accumulation. An axial T2* MR image (D) in case 3 shows iron deposition in the substantia nigra (arrowheads).

Fig 3.

Axial FLAIR MR images show varying degrees of white matter lesions. Patients 1 and 26 (A and B) show a mild degree of white matter lesions, with faint periventricular (A; arrows) and small scattered signal intensities (B; arrows). In patient 4 (C), images show patchy signal intensities (arrows), representing a moderate degree of white matter lesions. A more diffuse, vanishing high signal intensity (arrows) is seen in images (D) for patient 7.

Fig 4.

Axial (A) and coronal (B) FLAIR MR images for case 24 show white matter changes with frontal predominance (arrows). Axial FLAIR images show signal intensities (arrows) involving the pons (C) in patient 19 and the cerebellum (D) in patient 26.

Fig 5.

Axial T2 images show type I (A) and type III (B) prominent perivascular spaces.

Fig 6.

Axial DWI (A) and ADC map (B) sequences show diffusion restriction involving the splenium of corpus callosum.