Borealin/CDCA8 deficiency alters thyroid development and results in papillary tumor-like structures.

Background: BOREALIN/CDCA8 mutations are associated with congenital hypothyroidism and thyroid dysgenesis. Borealin is involved in mitosis as part of the Chromosomal Passenger Complex. Although BOREALIN mutations decrease thyrocyte adhesion and migration, little is known about the specific role of Borealin in the thyroid. Methods: We characterized thyroid development and function in Borealin-deficient (Borealin +/-) mice using histology, transcriptomic analysis, and quantitative PCR. Results: Thyroid development was impaired with a hyperplastic anlage on embryonic day E9.5 followed by thyroid hypoplasia from E11.5 onward. Adult Borealin +/- mice exhibited euthyroid goiter and defect in thyroid hormone synthesis. Borealin +/- aged mice had disorganized follicles and papillary-like structures in thyroids due to ERK pathway activation and a strong increase of Braf-like genes described by The Cancer Genome Atlas (TCGA) network of papillary thyroid carcinoma. Moreover, Borealin +/- thyroids exhibited structural and transcriptomic similarities with papillary thyroid carcinoma tissue from a human patient harboring a BOREALIN mutation, suggesting a role in thyroid tumor susceptibility. Conclusion: These findings demonstrate Borealin involvement in critical steps of thyroid structural development and function throughout life. They support a role for Borealin in thyroid dysgenesis with congenital hypothyroidism. Close monitoring for thyroid cancer seems warranted in patients carrying BOREALIN mutations.

Ultrasound and Fetal MRI Complementary Contributions to Appropriate Counseling in Small Bowel Obstruction.

OBJECTIVE: Bowel obstructions beyond the duodenum represent a heterogeneous group of congenital anomalies with a highly variable prognosis, the main issue being postnatal short bowel syndrome (SBS). The objective of our study was to evaluate the contributions of fetal MRI in cases of bowel obstruction. MATERIALS AND METHODS: A retrospective analysis of all newborns, for whom both ante-natal ultrasound and fetal MRI were available, referred to our center for suspected bowel obstruction was performed. Examinations were reviewed blinded to the postnatal outcome. Key outcome measures included exact diagnosis and the existence of postoperative SBS. We evaluated the contribution of MRI in determining precise location and etiology of the bowel obstruction, dilatation of the proximal bowel loops, and assessment of the quality of the remaining distal bowel loops. RESULTS: Twenty-five newborns were included. There were 19 single obstructions and 6 complex forms (4 apple peel syndromes and 2 multiple atresias). MRI correctly identified the affected segment of the small bowel in 59.1% of the cases. MRI identified the mechanism of obstruction in 72% of cases. MRI reliably predicted an abnormal appearance of the bowel distal to the obstruction in 100% of the severe cases (3/3) and in 66.7% of complex forms (4/6). CONCLUSION: Our study suggests that fetal MRI, when done in addition to prenatal ultrasound, is contributory in the management of fetuses with suspected bowel obstruction. MRI may be particularly useful in determining the location and origin of the bowel obstruction and in assessing the quality of the bowel distal to the obstruction, which might assist in the prediction of SBS and more detailed prenatal counseling.

Prenatal management of fetal goiter alternating between hypothyroidism and hyperthyroidism in a mother with Graves' disease.

We present a rare documented case with consecutive hypo- and hyperthyroidism during fetal life. First, hypothyroidism was due to transplacental passage of antithyroid drugs. After the mother's thyroidectomy, fetal hyperthyroidism was due to transplacental passage of persistent anti-thyrotropin receptor antibodies. Fetal goiter disappeared after adjusting maternal treatment.