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Teratogenetic polymalformative syndrome including malformations of the head and face, heart (conotruncal defects and aortic arch anomalies), and central nervous system (hydrocephalus and posterior fossae anomalies), resulting from maternal treatment for acne with isotretinoin (vitamin A analogue).

Microtia-Aortic Arch Syndrome; Fetal Retinoid Syndrome; Accutane Embryopathy.

More than 200 cases reported in the United States.

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.

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 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.

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.

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).

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 should be given in order to prevent graft-versus-host disease (high incidence).

Despite the presence of micrognathia (usually mild) and cleft palate, direct laryngoscopy and tracheal intubation in these patients usually is performed without difficulty. In case of hydrocephalus with increased intracranial pressure, rapid tracheal intubation and moderate hyperventilation should be used to lower the intracranial pressure; however, this should be weighed against the disadvantage of decreasing the pulmonary vascular resistance in the presence of congenital heart disease. Plan for prolonged postoperative monitoring because of a high frequency of apneic episodes.

Titrate cautiously volatile anesthetics to prevent the cardiac depressant effects in the ...

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