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

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.

Detailed descriptions of the clinical phenotype are rare. The aim of this study was to describe the clinical phenotype of ATR-X syndrome.

Data was collected through questionnaires, interviews, physical examination and the study of medical records.

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.

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.