Xia-Gibbs syndrome (XGS) – AHDC1 gene

Xia-Gibbs syndrome (XGS), also known as AHDC1 related intellectual disability obstructive sleep apnea mild dysmorphism syndrome, is a neurological disorder characterized by hypotonia, mild to severe intellectual disability and developmental delay, particularly expressive language.

In some people with XGS, brain imaging tests show abnormalities in the structure of the brain, such as an abnormally thin corpus callosum. Other signs and symptoms of this syndrome may vary among affected individuals. Additional neurological features include ataxia, seizures, feeding problems, and sleep abnormalities, such as obstructive sleep apnea. Some affected individuals have characteristics of autism spectrum alterations or attention deficit hyperactivity disorder (ADHD). In addition, aggressive behavior, anxiety, inability to control impulses and self-injury may be common.

Xia-Gibbs syndrome can also affect physical development, including short stature; scoliosis; unusual facial features, such as a broad forehead, low or protruding ears, hypertelorism, eyelid fissures tilted up or down, a flat nasal bridge, or a thin upper lip. Other less frequent abnormalities may include craniosynostosis, unusually lax joints and flaccid skin.

This process is due to mutations in the AHDC1 gene (AT-hook DNA binding motif containing 1), located on the short arm of chromosome 1 (1p36.11-p35.3), which encodes a protein whose function is unknown. The AHDC1 protein is found in the nucleus of cells, and it is believed that it may participate in the control of the activity of other genes.

More than 25 mutations in the AHDC1 gene responsible for the development of XGS have been described. Most of the mutations described result in the synthesis of abnormally short AHDC1 proteins. Although the effects of these changes in the cells are not clear, these proteins can break down quickly, not be functional or can interfere with the function of AHDC1 proteins produced from the normal copy of the gene. Some people with XGS have a mutation that eliminates the AHDC1 gene (and other nearby genes), although it is unknown whether such mutations are determinants of the disease. It is believed that a reduction in the amount of functional AHDC1 protein inhibits the normal development of the brain and other body systems.

This process is inherited with an autosomal dominant pattern, which means that one copy of the altered gene in each cell is sufficient to express the process, and it is due to new mutations that occur in the gene during the formation of reproductive cells or early in embryonic development. Due to the form of inheritance, affected individuals have no history of the syndrome in their family.

Tests performed in IVAMI: in IVAMI we perform the detection of mutations associated with Xia-Gibbs syndrome (XGS), by means of the complete PCR amplification of the exons of the AHDC1 gene, and their subsequent sequencing.

Recommended samples: non-coagulated blood obtained with EDTA for separation of blood leucocytes, or a card with a dried blood sample (IVAMI can mail the card to deposit the blood sample).