title: Pregnancy in women heterozygous for MCT8 mutations: risk of maternal hypothyroxinemia and fetal care.
abstract: BACKGROUND
  Monocarboxylate transporter 8 (MCT8 or SLC16A2) mutations cause X-linked Allan-Herndon-Dudley syndrome. Heterozygous females are usually asymptomatic, but pregnancy may modify thyroid function and MCT8 is expressed in the placenta, suggesting that maternal and fetal abnormalities might develop even in the absence of MCT8 fetal mutation. Genetic counseling is so far based on X-linked transmission, and prenatal diagnosis is rarely performed.
  
  
  OBJECTIVE
  To describe thyroid function and the prenatal diagnosis in pregnant mothers harboring heterozygous MCT8 mutations and management of the persistent maternal hypothyroxinemia. Patients Two women heterozygous for MCT8 mutations (c.1690G>A and c.1393-1G>C) were monitored throughout pregnancy.
  
  
  METHODS
  Prenatal diagnosis included sex determination, direct MCT8 sequencing, and familial linkage analysis. Ultrasonography and hormonal assays for maternal thyroid function evaluation were performed serially during pregnancy. Neonatal thyroid hormonal status was assessed.
  
  
  RESULTS
  None of the three fetuses (two males and one female) carried MCT8 mutations. One of the two heterozygous mothers revealed gestational hypothyroxinemia, prompting early levothyroxine (l-T₄) therapy until delivery. The second heterozygous mother showed normal thyroid function but was preventively traited by l-T₄ and all of the three neonates had normal thyroid hormone levels and thyroid gland at birth, suggesting advantages of prenatal care and/or compensatory mechanisms.
  
  
  CONCLUSIONS
  Heterozygous MCT8 women should be monitored for requirement of l-T₄ therapy to prevent fetal and neonatal hypothyroidism and to avoid risk of potential cognitive delay due to gestational hypothyroxinemia. Moreover, when the disease-causing mutation is known and/or the first child is affected, prenatal diagnosis for male fetuses should be assessed early for MCT8 mutations by direct sequencing.
authors.affiliation: INSERM U845 Pediatric Endocrinology and Gynecology, Centre des Maladies Endocriniennes Rares de la Croissance, AP-HP, Necker-Enfants Malades Hospital, Université Paris Descartes, 75743 Paris, France.
authors.forename: Helton Estrela
authors.initials: HE
authors.lastname: Ramos
authors.forename: Melina
authors.initials: M
authors.lastname: Morandini
authors.forename: Aurore
authors.initials: A
authors.lastname: Carré
authors.forename: Elodie
authors.initials: E
authors.lastname: Tron
authors.forename: Corinne
authors.initials: C
authors.lastname: Floch
authors.forename: Laurent
authors.initials: L
authors.lastname: Mandelbrot
authors.forename: Nathalie
authors.initials: N
authors.lastname: Neri
authors.forename: Benoit
authors.initials: B
authors.lastname: De Sarcus
authors.forename: Albane
authors.initials: A
authors.lastname: Simon
authors.forename: Jean Paul
authors.initials: JP
authors.lastname: Bonnefont
authors.forename: Jeanne
authors.initials: J
authors.lastname: Amiel
authors.forename: Isabelle
authors.initials: I
authors.lastname: Desguerre
authors.forename: Vassili
authors.initials: V
authors.lastname: Valayannopoulos
authors.forename: Mireille
authors.initials: M
authors.lastname: Castanet
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D007231:Infant, Newborn; D008297:Male; D027501:Monocarboxylic Acid Transporters / Q000235:genetics*; D011247:Pregnancy; D011296:Prenatal Diagnosis; D012306:Risk; D027981:Symporters; D013960:Thyroid Function Tests
chemical_list: D027501:Monocarboxylic Acid Transporters; C090735:SLC16A2 protein, human; D027981:Symporters