methimazole and Facies

Carbimazole (CMZ) and its active metabolite methimazole (MMI) are antithyroid medications, which can result in MMI/CMZ embryopathy in susceptible individuals. The incidence of birth defects related to MMI/CMZ embryopathy remains unclear as several epidemiologic studies failed to prove a correlation, despite positive case-control studies and numerous case reports. Malformations reported in exposed individuals and commonly recognized as MMI/CMZ embryopathy include cutis aplasia of the scalp, choanal atresia, esophageal atresia (EA), tracheo-esophageal fistula (TEF), persistent vitelline duct, athelia/hypothelia, and subtle facial dysmorphisms including sparse or arched eyebrows. Here, we report on individuals with early pregnancy exposure to MMI, with microtia and various other anomalies associated with MMI embryopathy, suggesting that microtia is also seen with increased frequency after prenatal MMI exposure. Additional unusual malformations among our patients include a previously unreported type of TEF with three separate esophageal pouches and a fistula connecting the middle pouch to the trachea in one child, and absence of the gall bladder in another. An enlarged anterior fontanel was seen in three patients, and clinodactyly of the fifth finger was noted in three. The similarities between our three patients with microtia after MMI exposure and the two previously reported with microtia after CMZ exposure support the concept of microtia being related to the MMI/CMZ exposure. Recognition of microtia as a manifestation of MMI/CMZ embryopathy will likely increase the number of diagnosed cases and thus affect ascertainment. We propose diagnostic criteria for MMI/CMZ embryopathy, including the presence of at least one major characteristic finding.

Topics: Child, Preschool; Congenital Abnormalities; Congenital Microtia; Cranial Fontanelles; Ear; Facies; Female; Fetal Diseases; Humans; Infant; Infant, Newborn; Male; Methimazole; Pregnancy; Tracheoesophageal Fistula

It has been suggested that children prenatally exposed to methimazole may present some features in common but the phenotype remains to be defined. The reported facial features include upward slanted palpebral fissures, arched flared eyebrows and small nose with a broad bridge. Choanal atresia and other anomalies like esophageal atresia and aplasia cutis were also described with this embryopathy. Additionally, developmental delay was reported in some patients along with one of these major malformation. We present a patient with the mentioned facial features, developmental delay and radio-ulnar synostosis whose mother has been exposed to methimazole during pregnancy and any other ethiological cause could be recognize.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Antithyroid Agents; Facies; Humans; Infant; Male; Methimazole; Phenotype; Radiography; Radius; Synostosis; Ulna

Two sibs from an inbred Arab family are described with an autosomal syndrome of choanal atresia, hypothelia/athelia and thyroid gland anomalies overlapping Bamforth syndrome, ANOTHER syndrome and methimazole embryopathy. In one case the syndrome described was lethal. Cases with similar features are reviewed and genetic mutations discussed.

Topics: Abnormalities, Multiple; Child, Preschool; Choanal Atresia; Congenital Hypothyroidism; Facies; Female; Genes, Recessive; Humans; Infant; Infant, Newborn; Male; Methimazole; Nipples; Syndrome; Thyroid Gland