7775 Clinical Features of NKX2-1 Gene-Related Diseases

Abstract

Abstract Disclosure: S. Fukui: None. E. Tanimoto: None. N. Ujita: None. H. Miyagi: None. K. Yoshii: None. N. Yasuhiro: None. R. Horikawa: None. Background: Congenital hypothyroidism (CH) is the most common congenital endocrine disorder. The utilization of molecular genetic techniques has facilitated the detection of CH resulting from various single-gene mutations; NKX2-1 gene-related disease stands out as one etiology of symptomatic CH. We report the clinical course of three cases with CH caused by NKX2-1 pathogenic variants. Case 1: An 8-year-old boy. He was born at 40 weeks and six days of gestation, weighing 2845g, and was presented to our department by high TSH (76.1 µIU/mL) at newborn screening (NBS), and LT4 treatment was initiated. He showed motor developmental delay, and choreiform movements were exhibited at two years and 11 months without respiratory symptoms. Case 2: An 18-year-old female. She was born at 40 weeks and five days gestation, weighing 2680g, and was admitted to her previous hospital following poor weight gain at approximately six months. During hospitalization, she was initiated LT4 treatment with a TSH elevation(14.7μIU/mL). After receiving a diagnosis of idiopathic interstitial pneumonia, she was subsequently referred to our hospital. At the age of 11, an NKX2-1 mutation was identified. Case 3: An 18-year-old female. She was born at 41 weeks and three days of gestation, weighing 2364g.TSH elevation (27.9 µIU/ml) was detected at NBS, and LT4 treatment was started. Thyroid hormone levels were maintained within normal range. However, wheezing and tracheomalacia were noted around five months. Hypotonia and delayed motor development were evident, and an NKX2-1 mutation was identified at the age of 12 years. Discussion: Although NKX2-1 gene-related disorders can be readily suspected when typical symptoms of central nervous system, pulmonary, and thyroid dysfunction manifest concurrently, diagnosis is sometimes established later because of the diversity of the occurrence of these symptoms. Despite reports of choreiform movements being inevitable, they did not appear in Case 2.3 until the age of 18 years. Conversely, muscle hypotonia and delayed motor development were observed in all our cases. When atypical neurological symptoms combined with CH are observed, NKX2-1 gene-related disease should be considered since the disease is known to develop malignant tumors such as lung cancer and thyroid cancer, which can significantly affect the prognosis of patients. Conclusion: When muscle hypotonia and delayed motor development are observed in addition to hypothyroidism and respiratory symptoms, NKX2-1 gene-related disease should be suspected, and follow-up for complications, including malignancy, is essential after diagnosis. Presentation: 6/2/2024