National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

Nager acrofacial dysostosis


Other Names:
Mandibulofacial dysostosis, Treacher Collins type, with limb anomalies; Nager syndrome; AFD, Nager type; Mandibulofacial dysostosis, Treacher Collins type, with limb anomalies; Nager syndrome; AFD, Nager type; Preaxial acrofacial dysostosis; Nager acrofacial dysostosis syndrome; Split hand deformity-mandibulofacial dysostosis; Acrofacial dysostosis 1, Nager type See More
Categories:
Nager acrofacial dysostosis is a genetic disorder that affects the limbs and face. The signs and symptoms of Nager acrofacial dysostosis vary among affected individuals, even among those in the same family.[1][2] Treatment is tailored to the individual based upon their specific needs.[2] This condition is caused by mutations in the SF3B4 gene.[1] While most cases are sporadic (occurring in families with no prior history of the disorder), autosomal dominant and autosomal recessive inheritance have been reported.[3]
Last updated: 2/25/2014

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Showing of 72 |
Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Aplasia/Hypoplasia of the thumb
Absent/small thumb
Absent/underdeveloped thumb
[ more ] 		0009601
Delayed speech and language development
Deficiency of speech development
Delayed language development
Delayed speech
Delayed speech acquisition
Delayed speech development
Impaired speech and language development
Impaired speech development
Language delay
Language delayed
Language development deficit
Late-onset speech development
Poor language development
Speech and language delay
Speech and language difficulties
Speech delay
[ more ] 		0000750
Downslanted palpebral fissures
Downward slanting of the opening between the eyelids
0000494
Hearing impairment
Deafness
Hearing defect
[ more ] 		0000365
Hypoplasia of the maxilla
Decreased size of maxilla
Decreased size of upper jaw
Maxillary deficiency
Maxillary retrusion
Small maxilla
Small upper jaw
Small upper jaw bones
Upper jaw deficiency
Upper jaw retrusion
[ more ] 		0000327
Hypoplasia of the zygomatic bone
Cheekbone underdevelopment
Decreased size of cheekbone
Underdevelopment of cheekbone
[ more ] 		0010669
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ] 		0000347
Skeletal dysplasia 0002652
30%-79% of people have these symptoms
Abnormal nasal morphology
Abnormal of nasal shape
Abnormal of shape of nose
[ more ] 		0005105
Aplasia/Hypoplasia of the eyebrow
Absence of eyebrow
Lack of eyebrow
Missing eyebrow
[ more ] 		0100840
Atresia of the external auditory canal
Absent ear canal
0000413
Cleft palate
Cleft roof of mouth
0000175
Hypoplasia of the radius
Underdeveloped outer large forearm bone
0002984
Joint stiffness
Stiff joint
Stiff joints
[ more ] 		0001387
Lower eyelid coloboma
Cleft lower eyelid
Notched lower eyelid
[ more ] 		0000652
Microtia
Small ears
Underdeveloped ears
[ more ] 		0008551
Ptosis
Drooping upper eyelid
0000508
Respiratory insufficiency
Respiratory impairment
0002093
Sparse lower eyelashes
Scanty lower eyelashes
Thin lower eyelashes
[ more ] 		0007776
Wide mouth
Broad mouth
Large mouth
[ more ] 		0000154
5%-29% of people have these symptoms
Abnormality of cardiovascular system morphology 0030680
Abnormality of the lower limb
Lower limb deformities
0002814
Low-set, posteriorly rotated ears 0000368
Non-midline cleft lip 0100335
Patent ductus arteriosus 0001643
Phocomelia 0009829
Triphalangeal thumb
Finger-like thumb
0001199
Unilateral renal agenesis
Absent kidney on one side
Missing one kidney
Single kidney
[ more ] 		0000122
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Percent of people who have these symptoms is not available through HPO
Abnormality of the cervical spine
Abnormal cervical spine
0003319
Absent radius
Missing outer large bone of forearm
0003974
Absent thumb
Absent thumbs
0009777
Aganglionic megacolon
Enlarged colon lacking nerve cells
0002251
Aqueductal stenosis 0002410
Autosomal dominant inheritance 0000006
Bicornuate uterus
Heart shaped uterus
Heart-shaped uterus
[ more ] 		0000813
Broad hallux
Broad big toe
Wide big toe
[ more ] 		0010055
Cleft upper lip
Harelip
0000204
Clinodactyly
Permanent curving of the finger
0030084
Conductive hearing impairment
Conductive deafness
Conductive hearing loss
[ more ] 		0000405
Foot oligodactyly
Missing toes
0001849
Gastroschisis 0001543
Hallux valgus
Bunion
0001822
Hip dislocation
Dislocated hips
Dislocation of hip
[ more ] 		0002827
Hydrocephalus
Too much cerebrospinal fluid in the brain
0000238
Hypoplasia of first ribs
Small first rib
Underdeveloped first rib
[ more ] 		0006657
Hypoplasia of the epiglottis 0005349
Laryngeal hypoplasia 0008749
Limited elbow extension
Decreased elbow extension
Elbow limited extension
Limitation of elbow extension
Limited extension at elbows
Limited forearm extension
Restricted elbow extension
[ more ] 		0001377
Low-set ears
Low set ears
Lowset ears
[ more ] 		0000369
Malar flattening
Zygomatic flattening
0000272
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ] 		0000252
Midface retrusion
Decreased size of midface
Midface deficiency
Underdevelopment of midface
[ more ] 		0011800
Overlapping toe
Overlapping toes
Overriding toes
[ more ] 		0001845
Polymicrogyria
More grooves in brain
0002126
Posteriorly rotated ears
Ears rotated toward back of head
0000358
Preauricular skin tag 0000384
Premature birth
Premature delivery of affected infants
Preterm delivery
[ more ] 		0001622
Prominent nasal bridge
Elevated nasal bridge
High nasal bridge
Prominent bridge of nose
Prominent nasal root
Protruding bridge of nose
Protruding nasal bridge
[ more ] 		0000426
Radial deviation of finger 0009466
Radioulnar synostosis
Fused forearm bones
0002974
Retrognathia
Receding chin
Receding lower jaw
Weak chin
Weak jaw
[ more ] 		0000278
Scoliosis 0002650
Short stature
Decreased body height
Small stature
[ more ] 		0004322
Short toe
Short toes
Stubby toes
[ more ] 		0001831
Talipes equinovarus
Club feet
Club foot
Clubfeet
Clubfoot
[ more ] 		0001762
Tetralogy of Fallot 0001636
Toe syndactyly
Fused toes
Webbed toes
[ more ] 		0001770
Trismus
Lockjaw
0000211
Urticaria
Hives
0001025
Variable expressivity 0003828
Velopharyngeal insufficiency
Velopharyngeal incompetence
0000220
Showing of 72 |
Last updated: 7/1/2020
There is evidence that at least some cases of Nager acrofacial dysostosis are caused by heterozygous mutation in the SF3B4 gene which is located on chromosome 1q12-q21.[1]
Last updated: 2/25/2014
Most people with Nager acrofacial dysostosis are the first person in a family with the condition due to a new mutation.  In this case, the condition is described as sporadic and not inherited from the parents. People with Nager acrofacial dysostosis are still at risk for passing the condition on to their future children.[1][2][4]

There have been a few reports of families with Nager acrofacial dysostosis inherited with an autosomal dominant or autosomal recessive pattern of inheritance.

Autosomal dominant means each child of an affected parent has a 50-50 chance of inheriting the mutant gene. If a child does not inherit the mutant gene, he or she will not develop the disease and cannot pass it to subsequent generations.

Autosomal recessive means the parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition. These parents have a 25% chance with each pregnancy of having a child with Nager acrofacial dysostosis.
Last updated: 12/12/2017

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.
In infants with Nager acrofacial dysostosis who experience respiratory distress require immediate attention and may require a tracheostomy.  A tracheostomy is a surgical procedure on the neck that opens a direct airway through an incision in the windpipe.

Infants with feeding difficulties may require surgery and/or placement of a feeding tube (gastrostomy). Surgery can be performed to repair cleft palate and often micrognathia. Cosmetic surgery, especially for eyelids, can be performed to ensure complete closure of eyelids at night in order to prevent injury of the cornea.[2] Surgical treatment is best accomplished at a craniofacial center with expertise in plastic surgery, otolaryngology, orthodontics, and dentistry.[4] Hearing aids for individuals with conductive hearing loss should be offered. [2]
Last updated: 4/9/2010

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Differential diagnosis may include mandibulofacial dysostosis syndromes such as Treacher-Collins syndrome, and other acrofacial dysostoses (AFD) such as the AFD Catania type, the AFD Palagonia type, the AFD Genee-Wiedemann type, the AFD Rodriquez type as well as mandibulofacial dysostosis with microcephaly (see these terms). Patients with the oculoauriculovertebral (OAV) spectrum (see this term) may also have overlapping features.
Visit the Orphanet disease page for more information.

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • The Centers for Mendelian Genomics program is working to discover the causes of rare genetic disorders. For more information about applying to the research study, please visit their website.

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

Social Networking Websites

  • RareConnect is an online social network for patients and families to connect with one another and share their experience living with a rare disease. The project is a joint collaboration between EURORDIS (European Rare Disease Organisation) and NORD (National Organization for Rare Disorders). Click on the link above to view the community for limb differences.

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • The Children’s Hospital Boston has a information page on congenital limb defects. Click on the link above to view this information page.
  • Genetics Home Reference (GHR) contains information on Nager acrofacial dysostosis. This website is maintained by the National Library of Medicine.
  • More information on limb abnormalities can be found at the following link from MedlinePlus, the National Library of Medicine Web site designed to help you research your health questions.
  • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

In-Depth Information

  • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
  • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
  • PubMed is a searchable database of medical literature and lists journal articles that discuss Nager acrofacial dysostosis. Click on the link to view a sample search on this topic.

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. O'Neill MJF. ACROFACIAL DYSOSTOSIS 1, NAGER TYPE; AFD1. Online Mendelian Inheritance in Man. October 8, 2013; http://omim.org/entry/154400. Accessed 2/25/2014.
  2. Opitz J. Acrofacial dysostosis 1, Nager type. Orphanet Encyclopedia. 2003; http://www.orpha.net/data/patho/GB/uk-nager.pdf. Accessed 2/25/2014.
  3. Nager syndrome. Genetics Home Reference (GHR). July 2010; http://ghr.nlm.nih.gov/condition/nager-syndrome. Accessed 2/25/2014.
  4. Wulfsberg EA. Nager syndrome. In: Winters R et al.,. NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2002;