What Is Nager Syndrome?

  • Jessica TangBSc, Cancer Science, Oncology and Cancer Biology, University of Nottingham
  • Maariya Rachid DaudDoctor of Philosophy - PhD, Bioprocessing and Chemical Engineering, The University of Manchester


Nager syndrome, also known as Nager Acrofacial Dysostosis or acrofacial dysostosis 1 nager type, is a rare genetic condition affecting the development of bones and tissues in the face and hands. The characteristics of this condition are visibly apparent in children with some of the most common symptoms involving  an abnormal overbite of the upper teeth, down-sloping of the eyes and little to no eyelashes. These malformations commonly affect the breathing and feeding which can be life-threatening requiring immediate intervention. Infants with Nager syndrome may commonly face difficulties when learning how to speak. However, this usually does not affect their cognitive development and intelligence.1 

This article aims to explain the symptoms, causes and treatments for Nager syndrome. Unfortunately, there is currently no cure for Nager syndrome but the earlier it is recognised and treated, the better the chances of the child living a healthy and full life. 

Signs and symptoms 

The characteristics of Nager syndrome are apparent in childhood and will present signs of underdevelopment of limbs such as the hands, face and arms. These symptoms include:2

  • Small lower jaw resulting in difficulties in feeding and breathing 
  • Hearing loss 
  • Absence or small ears
  • Cleft palate resulting in difficulties of speaking clearly 
  • Underdevelopment of the thumbs leading to problems with grip and movement
  • Downward sloping eyes 
  • Lack of eyelashes 
  • Short forearms that can affect joint movement 

If Nager syndrome is left untreated, it will cause life-threatening complications due to the fact that some symptoms can affect breathing and feeding. Therefore, it’s important to address these concerns as soon as possible with a doctor to be directed to the appropriate treatment.

Syndromes with similar characteristics:

There are many other syndromes which resemble some of the characteristics of Nager syndrome including:1

  • Miller syndrome 
  • Treacher-Collins 
  • Pierre-Robin
  • Genee-Wiedemann 
  • Franceschetti-Zwahlen-Klien

Although all of these syndromes share defining characteristics of the face not forming properly, they can be distinguished from one another. For example, one common symptom of Miller Syndrome is its effect on the feet. This contrasts with Nager syndrome which rarely affects the feet. Additionally, Miller syndrome is caused by a mutation of the DHODH gene3 while Nager syndrome is caused by the SF3B4 mutation.4 A thorough diagnosis with a healthcare specialist will help determine the exact condition and rule out other conditions. The importance of a thorough diagnosis will help your child to receive the best care. 

What causes Nager syndrome?

A genetic mutation in the SF3B4 gene has been identified to cause the condition. SF3B4 gene gives instructions to make the SAP49 protein. SAP49 proteins help regulate a variety of cellular processes involved in cell growth and are particularly important for the cells that build bone and cartilage. Mutation in the SF3B4 gene prevents the production of the SAP49 protein, leading to development problems. Many studies have found more than half of patients with Nager syndrome have the SF3B4 gene mutation while the other half does not have the mutated gene so the exact cause is unclear. Other genes are thought to be involved in this condition4

Nager syndrome is inherited in an autosomal dominant manner (caused by the SF3B4 mutation), which means that having one copy of the faulty gene is enough to cause Nager syndrome4


A physical examination, genetic testing and family history for your child and yourself are usually expected when diagnosing Nager syndrome. Imaging techniques such as MRI, CT and X-ray may be recommended to monitor and examine bone growth and internal structures before and after treatments. 

Living with Nager syndrome

Individuals with Nager syndrome may have difficulties navigating their personal life as they could be subjected to social isolation, low self-esteem and feelings of insecurity. Although Nager syndrome is a rare condition, it’s important to bring awareness surrounding this rare condition to empower individuals and allow them to feel like they belong in their community. 

With early intervention and treatment, your child will be able to grow up with their friends with a normal life expectancy. 

If you’re a parent caring for a child with Nager syndrome, you may find it challenging and experience a wide range of emotions. It’s important to schedule regular visits with your child’s doctor to observe their development, especially in the first five years. Depending on the severity of the condition, there are different treatments available to alleviate possible side effects of the condition. 

Management and treatment 

As soon as Nager syndrome is recognised, it is expected that your child will begin treatment as advised by the multidisciplinary team. The multidisciplinary team will usually consist of:

  • Craniofacial surgeons (skull and face)
  • Plastic surgeons 
  • Dentists and orthodontists
  • Orthopaedic surgeons (include the bones and joints to help with movement)
  • Head and neck surgeons 
  • Speech and language therapist 
  • Audiologists
  • Geneticists
  • Developmental psychologists5

Most patients with Nager syndrome may have a speech impairment, learning difficulties, feeding problems and blocked airways causing a reduction in quality of life. It’s likely your child will need surgery shortly after they are born as they will have difficulties in their breathing and feeding. There are different treatments to help manage the condition including: 

  • Tracheostomy: A surgeon creates a hole in your child’s throat and inserts a tube into the opening allowing your child to breathe. Your child may experience difficulty in talking and eating at the beginning which can take some time to adapt. It’s important to keep the tube clean and free of mucus to avoid serious complications.
  • Gastrostomy:  An opening is created at the skin of the abdomen where a feeding tube is inserted into the stomach. A feed solution is delivered through the tube to allow the child to receive the nutrients they need to grow and develop. 
  • Craniofacial surgery: This surgery helps correct physical malformations such as the lower jaw, ears, downsloping eyes and cleft lip or palate5

As with all procedures, there’s a slight risk of complications such as bleeding and infections. The multidisciplinary team will discuss the best course of treatment and carefully take the appropriate measures to reduce the risks during surgery. Any concerns with the procedure must be discussed with your doctor. 

Further support

Although Nager syndrome is a rare condition, with an estimated incidence of 3 per 1,000,0007, it does not mean you should go through this alone. With no specific support group for patients with Nager syndrome, there’s a wide range of support groups with similar experiences they can access such as:  

  • Headlines - a support group in the UK for those affected by craniofacial development. 
  • REACH - a charity supporting children with upper limb deficiency. Provides a wealth of fun activities to encourage young children to embrace their differences 
  • National Deaf Children’s Society - supporting young children with hearing loss 
  • Genetic Alliance UK 

Support groups outside the UK:

These support groups can help bring awareness to Nager syndrome and offer resources to help people live normal lives with this disorder.


Nager syndrome is a rare condition affecting the development of the limbs, most commonly affecting the facial structures like the eyes, jaws and ears. Nager syndrome is a lifelong condition that can be well managed through early intervention and treatments. Individuals with Nager syndrome will need long-term monitoring, especially during childhood and adolescence. Despite the mental and physical challenges patients face, individuals with Nager syndrome can lead a fulfilling life. By promoting awareness of Nager syndrome, patients and families gain a better understanding of this disease and can push research forward to develop new treatments towards Nager syndrome.


  1. Abdollahi Fakhim S, Shahidi N, Mousaviagdas M. A Case Report: Nager Acrofacial Dysostosis. Iran J Otorhinolaryngol [Internet]. 2012 [cited 2023 Aug 10]; 24(66):45–50. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3846201/
  2. Nager Syndrome - Symptoms, Causes, Treatment | NORD [Internet]. [cited 2023 Aug 10]. Available from: https://rarediseases.org/rare-diseases/nager-syndrome/
  3. Rainger J, Bengani H, Campbell L, Anderson E, Sokhi K, Lam W, et al. Miller (Genee-Wiedemann) syndrome represents a clinically and biochemically distinct subgroup of postaxial acrofacial dysostosis associated with partial deficiency of DHODH. Human Molecular Genetics [Internet]. 2012 [cited 2023 Aug 10]; 21(18):3969–83. Available from: https://academic.oup.com/hmg/article-lookup/doi/10.1093/hmg/dds218
  4. Petit F, Escande F, Jourdain AS, Porchet N, Amiel J, Doray B, et al. Nager syndrome: confirmation of SF3B4 haploinsufficiency as the major cause. Clin Genet. 2014; 86(3):246–51. Available from: https://pubmed.ncbi.nlm.nih.gov/24003905/
  5. Tsoukalas N, Johnson CD, Engelmeier RL, Delattre VF. The dental management of a patient with a cocaine-induced maxillofacial defect: a case report. Special Care in Dentistry [Internet]. 2000 [cited 2023 Aug 10]; 20(4):139–42. Available from: https://onlinelibrary.wiley.com/doi/10.1111/j.1754-4505.2000.tb01150.x.
  6. Zhao J, Yang L. Broad‐spectrum next‐generation sequencing‐based diagnosis of a case of Nager syndrome. J Clin Lab Anal [Internet]. 2020 [cited 2023 Aug 10]; 34(9):e23426. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7521291/.
This content is purely informational and isn’t medical guidance. It shouldn’t replace professional medical counsel. Always consult your physician regarding treatment risks and benefits. See our editorial standards for more details.

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Jessica Tang

Bachelor of Science - BSc Cancer Sciences, University of Nottingham

Jessica holds a Bachelor’s degree in Cancer Sciences with proficiency in bioinformatics and laboratory techniques. Her research project investigated the role of DARPP-32 and the associated genes and signalling pathways in ER+ breast cancer through RNA sequencing.

She is passionate about effectively communicating complex medical information to diverse audiences, bridging the gap between scientific expertise and public understanding. Jessica is an aspiring medical writer and looks forward to opportunities where she can utilise her expertise to drive meaningful change in the healthcare industry.

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