Neuroradiologic Features in X-linked α-Thalassemia/Mental Retardation Syndrome

Abstract

BACKGROUND AND PURPOSE: X-linked ␣-thalassemia/mental retardation syndrome (Mendelian Inheritance in Man, 301040) is one of the X-linked intellectual disability syndromes caused by mutations of the ATRX gene and characterized by male predominance, central hypotonic facies, severe cognitive dysfunction, hemoglobin H disease (␣-thalassemia), genital and skeletal abnormalities, and autistic and peculiar behavior. More than 200 patients in the world, including Ͼ70 Japanese patients, have been diagnosed with ATR-X syndrome.

Alpha-thalassemia X-linked intellectual disability syndrome identified by whole exome sequencing in two boys with white matter changes and developmental retardation

“…Our index cases showed remarkable widespread white matter 209 changes on brain MRI. These findings supported the previous sugges-210 tion that ATRX is involved in normal myelination, or the mutated pro-211 tein affects the expression of other proteins during myelination 212 (Wada et al, 2013). Therefore, we emphasize the importance of brain Korea to date (Yun et al, 2011).…”

“…Since the typical case was first de-49 scribed in 1990 (Wilkie et al, 1990), a broad spectrum of atypical clini-50 cal manifestations was noted (Pavone et al, 2010;Basehore et al, 2014). 51 Moreover, Wada et al recently reported various neuroimaging findings 52 of ATRX syndrome, which included white matter abnormalities, as well 53 as nonspecific brain atrophy (Wada et al, 2013). 54 In this study, we present two cases of genetically confirmed ATRX 55 syndrome that were identified by whole-exome sequencing ( …”

“…They were able to walk without assistance later in the course of the disease, although they displayed delayed motor development and cognitive impairment.Therefore, it may not be straightforward to suspect ATRX syndrome in cases with such atypical presentations, even after serial work-up to establish a diagnosis and identify disease etiology based on careful history taking, physical/neurological examination, and radiological findings.The two missense mutations in ATRX are located in the helicase Cterminal domain and expected to alter protein function. The white matter abnormalities detected on brain MRI, as well as the milder clinical features of these patients, might be associated with the location of the mutations(Badens et al, 2006;Wada et al, 2013). Considering the milder phenotypes or various radiological findings of the cases, there might remain undiagnosed cases of ATRX syndrome, although the disease is rare and only single case with thalassemia has been reported in…”

Neuroimaging Findings in Pediatric Genetic Skeletal Disorders: A Review

“…General information: X‐linked intellectual disability syndrome due to ATRX mutations on Xq13.3. More than 200 patients reported by 2012 …”

Thalassemia and risk of dementia: A nationwide population-based retrospective cohort study

“…However, these studies have focused on acquired anemia, whereas few studies have focused on hereditary anemia. Previous studies with small sample sizes have demonstrated a trend of developing cognitive dysfunction in severe types of thalassemia and the hemoglobin mutations associated with β thalassemia minor [11][12][13]. However, studies elucidating the relationship between thalassemia and long-term dementia incidence are rare.…”