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At a glance

Teratogenetic polymalformative syndrome includ­ing malformations of the head, ears, and face. The most significant condition include the heart (conotruncal defects and aortic arch anomalies), and central nervous system (hydrocephalus and posterior fossae anomalies). This is caused by isotretinoin (vitamin A analogue) during pregnancy for the treatment of acne.

Synonyms

Microtia-Aortic Arch Syndrome; Fetal Retinoid Syndrome; Accutane Embryopathy; Isotretinoin Embryopathy-Like Syndrome; Syndrome of Microtia and Aortic Arch Anomalies; Isotretinoin-Like Syndrome; Kawashima Syndrome.

Incidence

The prevalence for this medical condition is estimated at less than 1:1,000,000 worldwide. The age of onset of the symptoms is neonatal and infancy period. The National Institute of Health in the United States reports that this medical condition is present in approximately 200 cases.

Genetic inheritance

Only a few cases of genetic inheritance, presenting as an autosomal or X-linked Recessive Syndrome of microtia and aortic arch anomalies resembling isotretinoin embryopathy, have been described (so-called Microtia-Aortic Arch Syndrome). This report is about a Japanese mother who did not consume any vitamin A derivative during pregnancy and who had three children with the syndrome.

Pathophysiology

Maternal use of isotretinoin for treatment of severe acne during the first trimester of pregnancy exposes the fetus to a 25-fold increased relative risk for malformations. These malformations involve ears, facial skeleton, heart, and/or central nervous system. Cellular retinoic acid-binding proteins are found in high concentration in both central nervous system (CNS) and neural crest cells, possibly accounting for their susceptibility to isotretinoin toxicity. Isotretinoin might interfere with migration and proliferation of the neural crest cells, causing defects in branchial arch derivatives because of deficient mesenchyme.

Diagnosis

Physical appearance; history of maternal use of retinoic acid; cardiac evaluation for conotruncal heart defects and aortic arch abnormalities (echocardiogram and/or angiography); early neurologic evaluation (posterior fossa anomalies, hydrocephalus). Normal lymphocytes and calcium levels eliminate the possibility of DiGeorge Syndrome.

Clinical aspects

Malformations of the head and face: prominent frontal bossing, anotia or microtia, low-set ears, telecanthus, microphthalmia, depressed nasal bridge, micrognathia, and cleft palate. Central nervous system malformations: Dandy-Walker with associated aqueductal stenosis and hydrocephalus, cerebellar vermis hypogenesis or agenesis, and mental retardation. Cardiovascular malformations: double-outlet right ventricle, ventricular septal defect, tetralogy of Fallot, patent ductus arteriosus, persistent left superior vena cava, aortic coarctation (often preductal), and occasionally lymphoid system hypoplasia (thymic aplasia with ectopic focus, generalized lymphopenia).

Precautions before anesthesia

Airway assessment: cleft palate, micrognathia. Inquire about episodes of apnea; sleep studies often reveal both central and obstructive apnea. Obtain a cardiovascular evaluation including echocardiogram/angiography. Administer prophylactic antibiotics for congenital heart defects. Obtain neurologic evaluation: CT scanner/MRI (Dandy-Walker, hydrocephalus). Inquire about thymic aplasia. If a blood transfusion is anticipated for the surgery, only irradiated blood components ...

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