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

• Syndrome of Microtia and Aortic Arch Anomalies
• Microtia Aortic Arch Syndrome

What is Isotretinoin Embryopathy-Like Syndrome? (Definition/Background Information)

• Isotretinoin-like syndrome is a phenocopy of the Isotretinoin Embryopathy. It is characterized by the same anomalies as those described after maternal treatment with the drug isotretinoin (a vitamin A analog used for treatment of acne)
• These include malformations of the face (small, malformed, or missing ears, micrognathia, cleft palate), conotruncal heart defects, aortic arch anomalies, and central nervous system anomalies (hydrocephalus and posterior fossa abnormalities)
• Prenatal diagnosis may be performed by ultrasonography with careful examination of facial and cardiac structures
• As the syndrome has only been reported in males, X-linked recessive inheritance is possible, but autosomal recessive inheritance cannot be ruled out

(Source: Isotretinoin Embryopathy-Like Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Isotretinoin Embryopathy-Like Syndrome? (Age and Sex Distribution)

• Isotretinoin Embryopathy-Like Syndrome is a very rare congenital disorder described in 6 males so far, with 3 of the 6 being siblings 
• The presentation of symptoms may occur at birth
• So far, the condition has been reported to predominantly affect males
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Isotretinoin Embryopathy-Like Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Isotretinoin Embryopathy-Like Syndrome can be inherited
• Currently, no other risk factors have been clearly identified for the 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 Isotretinoin Embryopathy-Like Syndrome? (Etiology)

• The exact genetic cause of Isotretinoin Embryopathy-Like Syndrome is not known at the present time
• Based on the existing cases, it is theorized that the inheritance can either be X-linked recessive or autosomal recessive

X-linked recessive mode of inheritance: The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Autosomal recessive mode of inheritance: 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 Isotretinoin Embryopathy-Like Syndrome?

The signs and symptoms of Isotretinoin Embryopathy-Like Syndrome may include:

• Abnormality of the posterior cranial fossa
• Anotia
• Cleft palate
• Conotruncal defect
• Hydrocephalus
• Micrognathia
• Microtia

(Source: Isotretinoin Embryopathy-Like Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Isotretinoin Embryopathy-Like Syndrome Diagnosed?

The diagnosis of Isotretinoin Embryopathy-Like Syndrome may be made on the basis of:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary
• Diagnosis may be suspected in patients with a conotruncal heart and ear anomalies. Computed tomography of the temporal bone may reveal agenesis of the external auditory canals and bilateral ossicular chain abnormalities

(Source: Isotretinoin Embryopathy-Like Syndrome; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

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 Isotretinoin Embryopathy-Like Syndrome?

The complications of Isotretinoin Embryopathy-Like Syndrome may include:

• Hearing loss
• Abnormalities in heart function due to structural defects in the heart

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

How is Isotretinoin Embryopathy-Like Syndrome Treated?

There is no cure for Isotretinoin Embryopathy-Like Syndrome, since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops.

How can Isotretinoin Embryopathy-Like Syndrome be Prevented?

Currently, Isotretinoin Embryopathy-Like Syndrome may not be preventable, since it is a genetic disorder.

• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Prenatal ultrasound imaging of the developing fetus, with special emphasis in cardiac and facial structures may be possible
• 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 Isotretinoin Embryopathy-Like Syndrome? (Outcomes/Resolutions)

• The prognosis of Isotretinoin Embryopathy-Like Syndrome Survival may be determined by the type and severity of signs and symptoms, and complications if any
• The outcome may be determined by the severity of structural and functional defects in the heart
• No long-term follow-up data are available for this condition at the present time

Additional and Relevant Useful Information for Isotretinoin Embryopathy-Like Syndrome:

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

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