SNP Shot: Genomic Insights

Schinzel-Giedion syndrome is a serious condition present from birth that affects many systems in the body. Its characteristics include distinct facial features, neurological issues, and abnormalities of organs and bones. Due to the severity of these health problems, most individuals with this syndrome do not live beyond childhood.

Children affected by Schinzel-Giedion syndrome exhibit a range of distinctive features. A common characteristic is midface retraction, giving the appearance that the middle of the face is drawn inward. Other facial features may include a prominent or bulging forehead, widely spaced eyes (ocular hypertelorism), a short, upturned nose, and a wide mouth with an enlarged tongue (macroglossia). Additional distinctive features can include larger-than-normal spaces between the skull bones in infants (fontanelles), a short neck, low-set ears, and an inability to produce tears (alacrima). Excessive hairiness (hypertrichosis) is often present in babies with Schinzel-Giedion syndrome, though this usually disappears during infancy.

Significant developmental delays are common in children with Schinzel-Giedion syndrome. Other neurological problems can include severe feeding difficulties, seizures, or impairments in vision or hearing. They may also experience episodes of interrupted breathing during sleep (sleep apnea).

Individuals with this syndrome may also have organ abnormalities affecting the heart, kidneys, or genitals. Heart defects can involve problems with the heart valves (regulating blood flow), the heart chambers that pump blood (ventricles), or the wall separating the two sides of the heart (septum). Hydronephrosis, a buildup of urine in the kidneys, is frequent in children with Schinzel-Giedion syndrome and can affect one or both kidneys. Genital abnormalities, such as underdevelopment (hypoplasia), may also occur. In affected boys, the opening of the urethra may be located on the underside of the penis (hypospadias).

Bone abnormalities are frequently observed in individuals with Schinzel-Giedion syndrome. The bones at the base of the skull are often abnormally hard or thick (sclerotic), or the joint (occipital synchondrosis) between these bones may be abnormally wide. Furthermore, affected individuals may have broad ribs, abnormal collarbones (clavicles), clubfeet (inward- and upward-turning feet), or shortened bones in the arms or legs, particularly at the ends of the fingers (hypoplastic distal phalanges).

Children with Schinzel-Giedion syndrome who survive infancy have an increased risk of developing certain types of brain tumors known as neuroepithelial tumors.

Inheritance:

Schinzel-Giedion syndrome is caused by new mutations in the SETBP1 gene and arises in individuals with no family history of the condition. Only one copy of the altered gene in each cell is sufficient to cause the syndrome.