Case Report: Functional Analysis and Neuropsychological Evaluation of Dyshormonogenetic Fetal Goiter in Siblings Caused by Novel Compound Hyterozygous TPO Gene Mutations

IntroductionIt is rare for a euthyroid mother to carry a child with a fetal goiter. However, cases of congenital hypothyroidism (CH) caused by thyroid dyshormonogenesis have been reported. Even though gene mutations associated with fetal goiter have been reported in a few studies, the effects on intellectual development have not been investigated. This study aimed to characterize and investigate the underlying genetic mechanism of CH and neuropsychological development and growth of two siblings with CH-induced fetal goiters.Case reportTwo male siblings from a non-consanguineous marriage with CH and fetal goiter were diagnosed by ultrasonography at 32- and 26-weeks of gestation. This condition was confirmed by cordocentesis in the first pregnancy (TSH: 135 μIU/ml). The mother was euthyroid, and no intra-amniotic levothyroxine treatment was performed. Peripheral blood DNA was screened for TPO mutations. The new deletion p.Cys296Alafs*21 and the p.Arg665Trp mutation, inherited from heterozygous parents, were identified in both patients. Functional analysis showed both mutations reduced the TPO enzyme activity and impaired the membrane localization. The p.Cys296Alafs*21 mutation produces a protein product with a drastically reduced molecular weight. Additionally, a complete clinical and neuropsychological evaluation was also performed. The WISC IV test was employed to provide an overall measure of the siblings’ cognitive and intellectual abilities. No growth retardation was detected in either child. In general, both children showed normal neuropsychological development; however, they exhibited slight reduction of Processing Speed Index scores, which are sensitive to neurological and attentional factors and motor maturation activity. Notably, the younger sibling obtained significantly low scores in the Operational Memory Index, a measure of attention capacity and psychoneurological immaturity.ConclusionWe described a new TPO compound heterozygosity that severely impaired the TPO activity and membrane localization leading to severe CH and fetal goiter. This is the first report showing the neuropsychological evaluation in patients with dyshormonogenetic fetal goiter. More studies are needed to understand the neurodevelopmental outcomes of neonates with CH-induced fetal goiters.

Excessive Prenatal Supplementation of Iodine and Fetal Goiter: Report of Two Cases Using Three-dimensional Ultrasound and Magnetic Resonance Imaging

Fetal thyroid complications in pregnancy are uncommon, and are commonly related to the passage of substances through the placenta. The excessive iodine intake during the pregnancy is a well-known mechanism of fetal thyroid enlargement or goiter, and invasive procedures have been proposed for the treatment of fetal thyroid pathologies. In the present report, we demonstrate two cases from different centers of prenatal diagnosis of fetal thyroid enlargement and/or goiter in three fetuses (one pair of twins, wherein both fetuses were affected, and one singleton pregnancy). The anamnesis revealed the ingestion of iodine by the patients, prescribed from inadequate vitamin supplementation. In both cases, the cessation of iodine supplement intake resulted in a marked reduction of the volume of the fetal thyroid glands, demonstrating that conservative treatment may be an option in those cases. Also, clinicians must be aware that patients may be exposed to harmful dosages or substances during pregnancy.

Iatrogenic fetal goiter. Conservative management and spontaneous resolution

ObjectivesWe aim to report a case of a fetal goiter with postpartum spontaneous resolution. Fetal goiter can be secondary to maternal treatment and range from clinically asymptomatic or cause alterations in the fetus, from impaired swallowing to difficulty in vaginal delivery and even perinatal asphyxia due to the mass effect. The need for intrauterine treatment remains controversial.Case presentationWe present a case of fetal goiter with postpartum resolution. A 34-year-old multigravida presented to the emergency department with hiperemesis gravidarum at 10 weeks’ gestation. During evaluation for severe vomiting, Graves disease was diagnosed and treated with propylthiouracil. A routine ultrasound scan at 28 weeks gestation revealed a fetal anterior neck mass suggesting a fetal goiter. Cordocentesis showed fetal iatrogenic hypothyroidism. Conservative treatment was decided. Pregnancy concluded uneventful and the mass resolved spontaneously in the newborn.ConclusionsThe fetal thyroid gland is a structure that usually goes unnoticed during the process of prenatal diagnosis. In cases of maternal Graves diseases, fetal thyroid needs monitoring during pregnancy and conservative treatment is an option. Fetal goiter should be searched for secondary to thyroid alterations of the gravida, and in selected cases it can be managed without intrauterine treatment.