ATR-X syndrome

Alpha thalassemia mental retardation syndrome (ATRX), also called alpha thalassemia X linked intellectual disability syndrome, nondeletion type or ATR X syndrome, is an X linked recessive condition associated with a mutation in the ATRX gene. Males with this condition tend to be moderately intellectually disabled and have physical characteristics including coarse facial features, microcephaly (small head size), hypertelorism (widely spaced eyes), a depressed nasal bridge, a tented upper lip and an everted lower lip. Mild or moderate anemia, associated with alpha thalassemia, is part of the condition. Females with this mutated gene have no specific signs or features, but if they do, they may demonstrate skewed X chromosome inactivation. Atr X Syndrome can also come with problems regulating Levels and normal bodily temperature regulation, the cause of this is widely debated but currently unknown, many children with Atr X may need oxygen support long term through their entire life but cases that require long term oxygen are rare, however many children with Atr x will require help with feeding such and NG/NJ tube feeding, this is not present in all cases however. Many kids will also have serious reflux problems, which can necessitate regular medical suction operations.

"The role of ATRX as a regulator of heterochromatin dynamics raises the possibility that mutations in ATRX may lead to downstream transcriptional effects across the complex of genes or repetitive regions involved in the global context of the disorder, in addition to explaining phenotypical differences in these patients. For example, ATRX mutations affect the expression of alpha globin gene cluster, causing alpha thalassemia." ATRX interacts with the transcription co factor DAXX and the alpha globin gene cluster. Together they are all responsible for depositing the histone H3.3 at telomeric and pericentromeric regions. They are also responsible for regulating gene expression at these regions. ATR X syndrome patients have no deletion in chromosome 16, a thalassemia is rare, and this syndrome is consistent with X linked recessive inheritance. However, both groups have similar phenotypes. The phenotypes resulting from ATR X are due to skewed x inactivation. When there is a XH2 mutation in the ATR X locus, this indicates Xist to inactivate the chromosome increasing the amount of heterochromatin in males. Epigenetics is also present among transcriptional regulators. ATR X is caused by XH2 mutations in the region Xq13.3, and XH2 belongs to the subgroup SNF2. This group is important for regulating the transcription of the alpha genes.

If ATR X is suspected based on symptoms, diagnosis can be done via Genome testing. If the results are conclusive with ATR X syndrome, female members of the same family will often be asked to partake in genome testing to see if anyone else in the family may possess this gene.