What are the other Names for this Condition? (Also known as/Synonyms)

• Acrofacial Dysostosis 1, Nager type
• Mandibulofacial Dysostosis, Treacher Collins type, with Limb Anomalies
• Preaxial Acrofacial Dysostosis

What is Nager Acrofacial Dysostosis Syndrome? (Definition/Background Information)

• Nager Acrofacial Dysostosis Syndrome is a genetic disorder that affects the limbs and face. The signs and symptoms of Nager Acrofacial Dysostosis Syndrome vary among affected individuals, even among those in the same family
• Treatment is tailored to the individual based upon their specific needs
• This condition is caused by mutations in the SF3B4 gene. While most cases are sporadic (occurring in families with no prior history of the disorder), autosomal dominant and autosomal recessive inheritance have been reported

(Source: Nager Acrofacial Dysostosis Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Nager Acrofacial Dysostosis Syndrome? (Age and Sex Distribution)

• Nager Acrofacial Dysostosis Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Nager Acrofacial Dysostosis Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Nager Acrofacial Dysostosis Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for this syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Nager Acrofacial Dysostosis Syndrome? (Etiology)

• There is evidence that at least some cases of Nager Acrofacial Dysostosis Syndrome are caused by heterozygous mutation in the SF3B4 gene which is located on chromosome 1q12-q21
• Most cases of Nager Acrofacial Dysostosis Syndrome have been sporadic. Sporadic means that the condition occurs for the first time in a family due to a new mutation. People with sporadic conditions tend to be the first person affected in his or her family; however, they are still at risk for passing the condition on to their future children
• There have been reports of families with Nager Acrofacial Dysostosis Syndrome demonstrating an autosomal dominant and others autosomal recessive pattern of inheritance

(Source: Nager Acrofacial Dysostosis Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Nager Acrofacial Dysostosis Syndrome?

Nager Acrofacial Dysostosis Syndrome is characterized by limb and facial anomalies.

Limb anomalies that are more commonly reported in people with the syndrome include:

• Underdeveloped or absent radius/thumbs
• Thumbs with two knuckles (triphalangeal thumbs)
• Joined radius and ulnar bones (radioulnar synostosis)

Facial anomalies that are more commonly reported in people with the syndrome include:

• Underdeveloped jaw (micrognathia)
• Underdeveloped cheekbones
• Downward slanting eyes
• Reduced number of eyelashes
• Small missing segment of the lower eyelid (eyelid coloboma)
• Lack of development of the internal and/or external ear
• Cleft palate

Complications of Nager Acrofacial Dysostosis Syndrome may include hearing problems due to abnormal internal and/or external ear development, and breathing and feeding difficulties in infancy due to micrognathia and cleft palate.

In general, the signs and symptoms of Nager Acrofacial Dysostosis Syndrome may include:

• Abnormality of the cervical spine
• Absent radius and/or absent thumb
• Aganglionic megacolon
• Aqueductal stenosis
• Bicornuate uterus
• Broad hallux
• Cleft upper lip
• Clinodactyly
• Conductive hearing impairment
• Foot oligodactyly
• Gastroschisis
• Hallux valgus
• Hip dislocation
• Hydrocephalus
• Hypoplasia of first ribs
• Hypoplasia of the epiglottis
• Laryngeal hypoplasia
• Limited elbow extension
• Low-set ears
• Malar flattening
• Microcephaly
• Midface retrusion
• Overlapping toe
• Polymicrogyria
• Posteriorly rotated ears
• Preauricular skin tag
• Premature birth
• Prominent nasal bridge
• Radial deviation of finger
• Radioulnar synostosis
• Retrognathia
• Scoliosis
• Talipes equinovarus
• Trismus
• Urticaria
• Velopharyngeal insufficiency

Very frequently present symptoms in 80-99% of the cases:

• Aplasia/hypoplasia of the thumb
• Delayed speech and language development
• Downslanted palpebral fissures
• Hearing impairment
• Hypoplasia of the maxilla
• Hypoplasia of the zygomatic bone
• Micrognathia
• Skeletal dysplasia

Frequently present symptoms in 30-79% of the cases:

• Abnormal nasal morphology
• Aplasia/hypoplasia of the eyebrow
• Atresia of the external auditory canal
• Hypoplasia of the radius
• Joint stiffness
• Lower eyelid coloboma
• Microtia
• Ptosis
• Respiratory insufficiency
• Sparse lower eyelashes
• Wide mouth

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of cardiovascular system morphology
• Abnormality of the lower limb
• Low-set, posteriorly rotated ears
• Non-midline cleft lip
• Patent ductus arteriosus
• Phocomelia
• Triphalangeal thumb
• Unilateral renal agenesis
• Ventricular septal defect

(Source: Nager Acrofacial Dysostosis Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Nager Acrofacial Dysostosis Syndrome Diagnosed?

Nager Acrofacial Dysostosis Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Nager Acrofacial Dysostosis Syndrome?

The complications of Nager Acrofacial Dysostosis Syndrome may include:

• Severe limb and facial abnormalities
• Heart abnormalities
• Immobility, walking difficulties

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Nager Acrofacial Dysostosis Syndrome Treated?

• In infants with Nager Acrofacial Dysostosis Syndrome 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
• Surgical treatment is best accomplished at a craniofacial center with expertise in plastic surgery, otolaryngology, orthodontics, and dentistry
• Hearing aids for individuals with conductive hearing loss should be offered

(Source: Nager Acrofacial Dysostosis Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Nager Acrofacial Dysostosis Syndrome be Prevented?

Currently, Nager Acrofacial Dysostosis Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Nager Acrofacial Dysostosis Syndrome? (Outcomes/Resolutions)

• The prognosis of Nager Acrofacial Dysostosis Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Nager Acrofacial Dysostosis Syndrome:

Nager Acrofacial Dysostosis Syndrome is also known by the following names:

• AFD, Nager type
• Nager Acrofacial Dysostosis
• Nager Syndrome
• Split Hand Deformity-Mandibulofacial Dysostosis

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/