NORD gratefully acknowledges Elizabeth McPherson, MD, Department of Medical Genetic Services, Marshfield Clinic, Marshfield, WI, for assistance in the preparation of this report.
Nager syndrome is a rare inherited disorder characterized by craniofacial malformations occurring in association with abnormalities of the thumb and forearm. Craniofacial malformations include underdevelopment of the cheekbones (malar hypoplasia) resulting in downward slanting palpebral fissures; incomplete development of the lower jaw (mandibular hypoplasia), causing the jaw to appear abnormally small (micrognathia); and small (microtia) and/or malformed (dysplastic) external ears (pinnae), often with a blind ending or absent external ear canals, resulting in hearing impairment (conductive hearing loss). Nager syndrome is distinguished from other forms of acrofacial dysostosis by the limb abnormalities, which are primarily on the thumb (radial) side of the hand and forearm including underdevelopment or absence of the thumbs and the radius bone in the forearm, and abnormal fusion of bones in the forearms (radioulnar synostosis). The fingers and the feet are usually normal. Intelligence is usually not affected. Nager syndrome is typically inherited as an autosomal dominant trait caused by mutations in the SF3B4
gene on chromosome 1q12-q21. Although an individual with Nager syndrome can transmit the condition to his/her children, many cases occur randomly (sporadic) as a new gene change (de novo mutation) in the family.
Nager syndrome was first described in the medical literature in 1948 by doctors Nager and De Reynier. Nager syndrome belongs to a group of disorders collectively known as acrofacial dysostoses or AFDs. These disorders are characterized by craniofacial and limb abnormalities. AFDs are generally broken down into preaxial and postaxial types. Nager syndrome is a preaxial form; the term preaxial refers to the bones of the arms and legs that are on the thumb and big toe sides of the body.
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