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Disease Profile

Nager acrofacial dysostosis

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Neonatal

ICD-10

Q75.4

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Mandibulofacial dysostosis, Treacher Collins type, with limb anomalies; Nager syndrome; AFD, Nager type;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Eye diseases;

Summary

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]

Symptoms

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.

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

Cause

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]

Diagnosis

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.

    Treatment

    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]

    Organizations

    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.

        Learn more

        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.
        • 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.
        • Genetics Home Reference (GHR) contains information on Nager acrofacial dysostosis. This website is maintained by the National Library of Medicine.
        • 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.

            References

            1. O'Neill MJF. ACROFACIAL DYSOSTOSIS 1, NAGER TYPE; AFD1. Online Mendelian Inheritance in Man. October 8, 2013; https://omim.org/entry/154400. Accessed 2/25/2014.
            2. Opitz J. Acrofacial dysostosis 1, Nager type. Orphanet Encyclopedia. 2003; https://www.orpha.net/data/patho/GB/uk-nager.pdf. Accessed 2/25/2014.
            3. Nager syndrome. Genetics Home Reference (GHR). July 2010; https://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;

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