Clinical variability in individuals with ATR-X syndrome in the Netherlands

Background: The Alpha Thalassemia mental Retardation syndrome, X-linked (ATR-X syndrome, MIM: 301040) is a rare genetic disorder characterized by alpha thalassemia, intellectual disability, peculier facial characteristics and genital abnormalities. Detailed information regarding the clinical phenotype is lacking. Aims: Detailed descriptions of the clinical phenotype are rare. The aim of this study was to describe the clinical phenotype of ATR-X syndrome. Methods: Data was collected through questionnaires, interviews, physical examination and the study of medical records. Results: Twenty-two individuals, aged 2–68 years old, were included. Three individuals were deceased at the time of the study. The individuals had a variable degree of intellectual disability. Alpha thalassemia was found in 30 % and genital anomalies in 70 % of the individuals. First clinical signs of the syndrome were most frequently feeding problems, started in the neonatal period in the majority. Other main reported health problems were reflux (59 %), constipation (72 %), periods of anorexia and adipsia (45 %), heart defects (28 %), epilepsy (33 %), scoliosis/kyphosis (48 %), visual impairment (61 %) and hearing loss (38 %). Behavioral problems (86 %) and sleeping problems (64 %) also occurred frequently. Conclusion: We report on the largest cohort of clinically studied individuals with ATR-X syndrome, including the eldest individuals, reported to date. Clinical knowledge is essential to improve care and to evaluate future therapies for this group.