Eliyahu Zaig MD, Odile Cohen-Ouaknine MD, Anat Tsur MD, Sheila Nagar MD, Gherta Bril MD, Lior Tolkin MD, Avivit Cahn MD, Mozhgan Heyman and Benjamin Glaser MD
Background: Reduced sensitivity to thyroid hormone (RSTH) syndrome describes a group of rare heterogeneous genetic disorders. Precise diagnosis is essential to avoid unnecessary treatment.
Objectives: To identify and characterize previously undiagnosed patients with RSTH in Israel.
Methods: Patients with suspected RSTH throughout Israel were referred for study. After clinical evaluation, genomic DNA was obtained and all coding exons of the thyroid hormone receptor beta (THRB) gene were sequenced. If mutations were found, all available blood relatives were evaluated. The common polymorphism rs2596623, a putative intronic regulatory variant, was also genotyped. Genotype/phenotype correlations were sought, and the effect of mutation status on pregnancy outcome was determined.
Results: Eight mutations (one novel; two de-novo, six dominant) were identified in eight probands and 13 family members. Clinical and genetic features were similar to those reported in other populations. Previous suggestions that rs2596623 predicts clinical features were not confirmed. There was no evidence of increased risk of miscarriage or fetal viability. Mothers carrying a THRB mutation tended to have increased gestational hypertension and low weight gain during pregnancy. Their affected offspring had increased risk of small-for-gestational age and poor postnatal weight gain.
Conclusions: Clinical heterogeneity due to THRB mutations cannot be explained by the variant rs2596623. Mothers and newborns with THRB mutations seem to be at increased risk of certain complications, such as gestational hypertension and poor intrauterine and postnatal growth. However, these issues are usually mild, suggesting that routine intervention to regulate thyroid hormone levels may not be warranted in these patients.
Vered Nir MD, Michal Gur MD, Yazeed Toukan MD, Fahed Hakim MD, Arcadi Vachyan MD and Lea Bentur MD
Background: Recurrence of tracheoesophageal fistula (TEF) is reported in 8–20% patients. Factors that may influence recurrence of fistula beyond the postoperative period are not clear.
Objectives: To evaluate possible factors associated with recurrence of TEF beyond the immediate postoperative period.
Methods: A single center, retrospective comparison of patients with and without recurrence of TEF was conducted. Medical records of patients previously operated for TEF who were followed in our pediatric pulmonary institute between January 2007 and December 2016 were reviewed.
Results: The medical records of 74/77 patients previously operated for TEF were evaluated. Nine patients (12%) had a recurrence of TEF and 65 did not. These groups had similar age and gender distribution and similar prevalence of VACTERL association. In addition, they had similar length of atretic gap, rates of thoracoscopic surgery, rates of prolonged need for respiratory assistance post-surgery, and frequency of gastrointestinal symptoms. Notably, the patients who had recurrent TEF had significantly more hospitalizations for respiratory symptoms (P = 0.011) and significantly more episodes of clinical bronchiolitis per patient (P < 0.0001). In addition, the patients with recurrent TEF had significantly more episodes of positive polymerase chain reaction for viruses (P = 0.009).
Conclusions: Hospitalizations for respiratory symptoms as well as clinical and/or viral bronchiolitis are associated with recurrence of TEF. Even though cause and effect cannot be established, these patients should undergo meticulous evaluation for the possibility of recurrence of TEF.
Christoph Robier MD, Omid Amouzadeh-Ghadikolai MD, Mariana Stettin MD and Gerhard Reicht MD
Nir Hod MD MHA, Reut Anconina MD, Daniel Levin MD, Ekaterina Tiktinsky MD, Dina Ezroh Kazap MD, Itai Levi MD, Maria Zektser MD, Vered Stavi MD, Gilbert Sebbag MD and Sophie Lantsberg MD
Florian Rey MD, Thibault Ronchard MD PharD, Jawad Chaara MD and Stéphane Noble MD
Jannis Kountouras MD PhD, Michael Doulberis MD DVM PhD, Stergios A. Polyzos MD PhD, Apostolis Papaefthymiou MD, Nikolaos Kapetanakis MD PhD, Stergios Arapoglou MD PhD, Ioannis Venizelos MD PhD, Elizabeth Vardaka PhD, Georgios Kotronis MD, Sotirios Anastasiadis MD and Panagiotis Katsinelos MD PhD
Haim Shmuely MD, Baruch Brenner MD, David Groshar MD, Nir Hadari MD, Ofer Purim MD, Meital Nidam MD, Merab Eligalashvili MD, Jacob Yahav MD and Hanna Bernstine MD