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 Ͻ .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. ABBREVIATIONS: NBIA ϭ neurodegenerative diseases with brain iron accumulation; WSS ϭ Woodhouse-Sakati syndrome; SNHL ϭ sensorineural hearing loss

Brain MRI Pattern Recognition in Neurodegeneration With Brain Iron Accumulation

“…T2 hyperintense white matter abnormalities were consistently found in the periventricular white matter with parietal predominance. In WSS, frontoparietal and periventricular white matter lesions were the most common non-iron abnormalities (65). And, older age was associated with a more severe degree of white matter lesions.…”

Woodhouse–Sakati Syndrome: First report of a Portuguese case

“…Insulin‐like growth factor 1 (IGF‐1) levels are low in all reported patients (Agopiantz et al, ; Alazami et al, ; Ali et al, ). Brain magnetic resonance imaging (MRI) commonly shows white matter abnormalities with variable extension and distribution, and also iron deposition in the basal ganglia, thus being considered a form of neurodegeneration with brain iron accumulation (Abusrair et al, ; Hogarth, ; Salomão et al, ). Nevertheless, patients can display a marked phenotypic variability.…”

“…The most commonly described imaging findings are a small pituitary gland, iron deposition in the globus pallidus, and nonenhancing frontoparietal/periventricular white matter lesions. Disease progression leads to further iron deposition, involving the red nucleus and substantia nigra, and to the expansion of white matter lesions (Abusrair et al, ). While our patient had periventricular white matter lesions and progressive iron deposition, there was significant pontine involvement, who is not a novel finding but has only been previously described in cases with severe leukodystrophy (Abusrair et al, ), further expanding the knowledge regarding brain MRI findings in WSS.…”

Endocrine Abnormalities in a Case of Neurodegeneration with Brain Iron Accumulation

“…1 The endocrine system is affected in virtually all patients with WSS. 3 The most common findings are hypogonadotropic hypogonadism, alopecia, DM, and primary hypothyroidism. 1 Involvement of the neurological system happens in more than half of the patients, with extrapyramidal symptoms, intellectual disability, and sensory neural hearing loss being most commonly reported.…”

“…1 Involvement of the neurological system happens in more than half of the patients, with extrapyramidal symptoms, intellectual disability, and sensory neural hearing loss being most commonly reported. 3,4 Parkinsonism and dystonia are the main extrapyramidal manifestations. 1 Seizure is an uncommon manifestation of WSS.…”