Nager syndrome is a rare, inherited condition affecting the development of the face, hands, and arms. It is a form of acrofacial dysostosis, characterized by craniofacial and limb abnormalities present from birth. The physical traits can vary among individuals but follow a recognizable pattern. This condition does not impact a person’s intelligence.
Physical Characteristics of Nager Syndrome
The features of Nager syndrome are most prominent in the face and limbs. Craniofacial development is affected, with underdeveloped cheekbones, known as malar hypoplasia, leading to a flattened midface. A characteristic is a very small lower jaw, or micrognathia, which can cause feeding and breathing difficulties in newborns. The eyes often slant downward, and there may be a notch in the lower eyelids, referred to as an eyelid coloboma.
Many individuals with this syndrome are born with an opening in the roof of their mouth, known as a cleft palate. External ear abnormalities are also common, ranging from small, unusually formed ears (microtia) to absent ear canals. These structural issues in the ear frequently lead to conductive hearing loss because sound cannot travel efficiently through the middle ear. Speech development can be delayed as a result.
Limb abnormalities primarily concern the arms and hands. Underdeveloped or completely absent thumbs are a characteristic feature of the condition. The forearms can be shortened, sometimes due to the absence of the radius bone, and the fusion of the two forearm bones (radioulnar synostosis) can occur, limiting the ability to rotate the forearm. Affected individuals may also find it difficult to fully extend their elbows.
The Genetic Origins
Nager syndrome arises from genetic mutations. In approximately half of documented cases, the condition is caused by a mutation in the SF3B4 gene. This gene provides instructions for a component of the cell’s splicing machinery, which processes genetic information to produce functional proteins. A mutation can disrupt this process, affecting development.
The condition is inherited in an autosomal dominant pattern, meaning one copy of the altered gene from a single parent is sufficient to cause the syndrome. In many instances, the genetic change is not inherited but occurs spontaneously as a de novo mutation. Researchers believe other unidentified genes may also be responsible, as the SF3B4 mutation is not found in all affected individuals.
Diagnosis and Management
Diagnosis of Nager syndrome often begins with a clinical evaluation at birth based on the infant’s distinct physical characteristics. Healthcare providers will assess the craniofacial and limb anomalies. To get a clearer picture of the underlying skeletal structure, imaging techniques such as X-rays are used to examine the bones in the jaw, arms, and hands.
For a definitive diagnosis, genetic testing is performed to identify a mutation in the SF3B4 gene. The presence of a pathogenic variant in this gene confirms the clinical findings. This genetic confirmation is also useful for family planning and understanding the inheritance pattern for future generations.
There is no cure for Nager syndrome, so treatment focuses on managing symptoms and improving function with a coordinated, multidisciplinary team of specialists. Craniofacial surgeons may perform procedures to address airway obstruction or repair a cleft palate. Orthodontists and dental specialists manage dental issues, while audiologists address hearing loss. Speech and occupational therapists help individuals overcome developmental delays and adapt to limb abnormalities.
Long-Term Outlook
While Nager syndrome presents physical challenges, particularly in infancy, the long-term outlook is positive. With successful management of the initial breathing and feeding problems, life expectancy is normal. Ongoing medical care from a team of specialists helps address health issues as they arise. With appropriate support, individuals with Nager syndrome can lead full and productive lives.