SNP Shot: Genomic Insights

Nager syndrome is a rare genetic disorder primarily affecting the development of the face, arms, and hands. The severity of the condition can vary significantly from person to person.

Infants with Nager syndrome typically exhibit underdeveloped cheekbones (malar hypoplasia) and a noticeably small lower jaw (micrognathia) at birth. A cleft palate, or opening in the roof of the mouth, is also frequently observed. These characteristics often lead to difficulties with feeding in infancy. Furthermore, the micrognathia can cause partial airway obstruction, potentially resulting in life-threatening breathing complications.

Common features of Nager syndrome include eyes that slant downward (downslanting palpebral fissures), absent eyelashes, and notches in the lower eyelids (eyelid colobomas). Many individuals also have small or abnormally shaped ears. Approximately 60% experience hearing loss due to defects in the middle ear, known as conductive hearing loss. While Nager syndrome doesn't impact intelligence, speech development may be delayed due to any associated hearing impairment.

Bone abnormalities in the hands and arms are characteristic of Nager syndrome. Malformed or missing thumbs are the most prevalent. Other potential abnormalities include unusually curved fingers (clinodactyly) or fingers that are fused together (syndactyly). The forearms may be shorter than usual due to the partial or complete absence of the radius bone. Limited extension of the elbows is also sometimes observed. In some instances, bone abnormalities may also affect the legs and feet.

Less frequently, individuals with Nager syndrome may have abnormalities affecting the heart, kidneys, genitalia, or urinary tract.

Inheritance:

When Nager syndrome is caused by mutations in the SF3B4 gene, it typically follows an autosomal dominant inheritance pattern. This means that only one copy of the mutated gene in each cell is enough to cause the disorder. In most cases, the mutation arises spontaneously, with no prior family history of the condition. Less commonly, the affected individual inherits the mutated gene from a parent who also has Nager syndrome. Mutations in other genes may also lead to autosomal dominant Nager syndrome. Nager syndrome can also show an autosomal recessive inheritance pattern, which means that both copies of a gene in each cell must be mutated for the condition to develop. In these instances, both parents are carriers of one mutated gene copy, but usually show no symptoms themselves. The possibility of autosomal recessive inheritance is suspected when unaffected parents have more than one child affected with Nager syndrome. However, the specific gene responsible in these families is currently unknown.