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

• AFFN Dysostosis 1
• Cleft Lip/Palate with Frontonasal Dysostosis and Postaxial Polysyndactyly
• Polysyndactyly, Postaxial, Frontonasal Dysostosis and Cleft Lip/Palate

What is Acrofrontofacionasal Dysostosis Syndrome? (Definition/Background Information)

• Acrofrontofacionasal Dysostosis Syndrome (AFFN Dysostosis Syndrome) is a congenital malformation syndrome characterized by the association of facial and skeletal anomalies with severe intellectual deficit and occasional genitourinary anomalies
• The cranio-facial malformations are numerous and variable. They include brachycephaly or microbrachycephaly, prominent forehead with low frontal and occipital hairline, wide anterior fontanel, hypertelorism, large philtrum, broad notched nasal tip, cleft lip, highly-arched palate, small ears with prominent helix, hypoplasia of mid-face, and prognathism
• Other skeletal malformations are also present, with syndactyly of fingers 3 and 4, hypoplastic 3rd, 4th and 5th toes, anomalies of feet structure and fibular hypoplasia. Short stature may be observed
• Eye anomalies include bilateral ptosis, coloboma of the upper lids, cataract, congenital glaucoma and iris atrophy. In some male patients, hypospadias, with or without cleft glans, and bifid scrotum are reported
• Patients suffer from potentially severe intellectual deficit and present with anomalies of the cortical gyration (without any corpus callosum abnormality). Encephalocele may occur
• Autosomal recessive transmission is probable. The etiology of AFFN Dysostosis Syndrome is unknown

(Source: Acrofrontofacionasal Dysostosis Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Acrofrontofacionasal Dysostosis Syndrome? (Age and Sex Distribution)

• Acrofrontofacionasal Dysostosis Syndrome is an extremely rare congenital disorder and a few cases (about 7) have been mainly reported from the nation of Brazil. However, so far, only about 12 cases have been recorded in the medical history
• 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 Acrofrontofacionasal Dysostosis Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Acrofrontofacionasal Dysostosis Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for AFFN Dysostosis 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 Acrofrontofacionasal Dysostosis Syndrome? (Etiology)

• The exact cause of development of Acrofrontofacionasal Dysostosis Syndrome is currently unknown
• Some research scientists believe that it is a genetic disorder that may be probably inherited in an autosomal recessive manner

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 Acrofrontofacionasal Dysostosis Syndrome?

The signs and symptoms of Acrofrontofacionasal Dysostosis Syndrome may include:

• Acetabular dysplasia
• Cleft upper lip
• Malar flattening
• Short metacarpal
• Small nail
• Wide mouth
• Wide nasal bridge

Obligate present symptoms in 100% of the cases:

• Hypertelorism
• Intellectual disability

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

• Abnormality of epiphysis morphology
• Anonychia
• Aplasia/hypoplasia of the eyebrow
• Brachycephaly
• Brachydactyly
• Broad forehead
• Broad nasal tip
• Broad thumb
• Brushfield spots
• Camptodactyly of finger
• Cerebral cortical atrophy
• Cleft eyelid
• Dimple on nasal tip
• Downslanted palpebral fissures
• High palate
• Hypopigmented skin patches
• Intellectual disability, severe
• Micromelia
• Midface retrusion
• Non-midline cleft lip
• Ptosis
• Short distal phalanx of finger

Frequently present symptoms in 30-79% of the cases: Everted lower lip vermilion

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

• Bifid scrotum
• Hypospadias
• Iris atrophy
• Long eyebrows
• Long eyelashes
• Microphthalmia
• Mixed hearing impairment
• Oligodontia
• Optic atrophy
• Pectus excavatum
• Seizures
• S-shaped palpebral fissures
• Widow's peak

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

How is Acrofrontofacionasal Dysostosis Syndrome Diagnosed?

Acrofrontofacionasal 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 Acrofrontofacionasal Dysostosis Syndrome?

The complications of Acrofrontofacionasal Dysostosis Syndrome may include:

• Vision and hearing impairment
• Intellectual impairment
• Infertility, in some cases, in males

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

How is Acrofrontofacionasal Dysostosis Syndrome Treated?

There is no cure for Acrofrontofacionasal Dysostosis Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complications that develops.

How can Acrofrontofacionasal Dysostosis Syndrome be Prevented?

Currently, Acrofrontofacionasal Dysostosis Syndrome may not be preventable, since it is believed to a genetic disorder. If there is a family history of the condition, then:

• Genetic counseling will help assess risks, before planning for a child
• 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
• 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 Acrofrontofacionasal Dysostosis Syndrome? (Outcomes/Resolutions)

• The prognosis of Acrofrontofacionasal 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 Acrofrontofacionasal Dysostosis Syndrome:

Acrofrontofacionasal Dysostosis Syndrome is also known by the following names:

• Acro-Fronto-Facio-Nasal Dysostosis (AFFN) Syndrome
• AFFN Dysostosis Syndrome

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

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