Shetty Vinutha B, Kiraly-Borri Cathy, Lamont Phillipa, Bikker Hennie, Choong Catherine S Y
J Pediatr Endocrinol Metab. 2014 Mar;27(3-4):373-8. doi: 10.1515/jpem-2013-0109.
Brain-lung-thyroid syndrome (BLTS) characterized by congenital hypothyroidism, respiratory distress syndrome, and benign hereditary chorea is caused by thyroid transcription factor 1 (NKX2-1/TTF1) mutations. We report the clinical and molecular characteristics of four cases presenting with primary hypothyroidism, respiratory distress, and neurological disorder. Two of the four patients presenting with the triad of BLTS had NKX2-1 mutations, and one of these NKX2-1 [c.890_896del (p.Ala327Glyfs*52)] is a novel variant. The third patient without any identified NKX2-1 mutations was a carrier of mitochondrial mutation; this raises the possibility of mitochondrial mutations contributing to thyroid dysgenesis. Although rare, the triad of congenital hypothyroidism, neurological, and respiratory signs is highly suggestive of NKX2-1 anomalies. Screening for NKX2-1 mutations in patients with thyroid, lung, and neurological abnormalities will enable a unifying diagnosis and genetic counseling for the affected families. In addition, identification of an NKX2-1 defect would be helpful in allaying the concerns about inadequate thyroxine supplementation as the cause of neurological defects observed in some children with congenital hypothyroidism.
脑-肺-甲状腺综合征（BLTS）以先天性甲状腺功能减退、呼吸窘迫综合征和良性遗传性舞蹈病为特征，由甲状腺转录因子1（NKX2-1/TTF1）突变引起。我们报告了4例表现为原发性甲状腺功能减退、呼吸窘迫和神经功能障碍患者的临床和分子特征。4例出现BLTS三联征的患者中有2例存在NKX2-1突变，其中1例NKX2-1 [c.890_896del (p.Ala327Glyfs*52)]是一种新的变异。第3例未发现任何NKX2-1突变的患者是线粒体突变携带者；这增加了线粒体突变导致甲状腺发育异常的可能性。虽然罕见，但先天性甲状腺功能减退、神经和呼吸体征三联征强烈提示NKX2-1异常。对甲状腺、肺部和神经异常患者进行NKX2-1突变筛查，将有助于为受影响家庭进行统一诊断和遗传咨询。此外，确定NKX2-1缺陷将有助于消除对一些先天性甲状腺功能减退儿童中观察到的神经缺陷是由甲状腺素补充不足所致的担忧。
