Congenital hypothyroidism (CH) is one of the most common endocrine disorders of childhood. The primary form of CH is attributable to thyroid dysgenesis (agenesis, hypoplasia, or ectopy) in 65-85% of cases, with the remaining cases being attributed to dyshormogenesis. Thyroid dysgenesis was considered a sporadic disease. However, the recent advantages of molecular techniques have significantly contributed to the understanding of the pathogenesis of the disease. The higher prevalence of congenital malformations and syndromes in patients with CH compared to the general population supports the genetic basis. This narrative review aims to provide an overview of the identified and potential genetic causes of thyroid dysgenesis. Mutations in ten genes involved in thyroid gland development during embryogenesis, TSHR, PAX8, NKX2-1, NKX2-5, FOXE1, JAG1, NTN1, GLIS3, CDC8A, and TUBB1, have been identified in cohorts of patients with thyroid dysgenesis. However, most cases remain unexplained. Novel candidate genes have been proposed. The extant evidence suggests that the pathogenesis of thyroid dysgenesis involves a spectrum of genetic etiologies, ranging from monogenic to multigenic, and that epigenetic or environmental factors may also contribute. As molecular techniques are continuously refined, future studies are expected to elucidate the complex genetic background of thyroid dysgenesis.

Hypothyroidism leads to a prolonged QT interval due to modulation of the potassium channel by low circulating T3, leading to a disproportionate lengthening of the action potential. Patients with long QT syndromes (LQTS) have an increased risk of symptomatic ventricular arrhythmias and sudden cardiac death (SCD). A 40-year-old female with a previous history of congenital LQTS, Type 1 diabetes mellitus, anaemia, and untreated hypothyroidism was brought to the hospital with an abrupt onset of palpitations and disorientation following multiple (>30) automated implantable cardioverter-defibrillator shocks with no identifiable triggers. Emergency medical services telemetry monitoring en route to the hospital revealed torsades de pointes (TdP), following which she received 4 g of magnesium sulfate intravenously and reverted to sinus rhythm. Electrocardiogram revealed sinus rhythm with a prolonged QTc of 515 ms. The laboratory testing revealed high TSH with low T4. The myxoedema coma score was markedly elevated at 40, indicating severe hypothyroidism. The thyroid peroxidase antibody was >600 IU/mL, indicating Hashimoto's thyroiditis. Echocardiography showed left ventricular ejection fraction of 55%-60% with no wall motion abnormalities. We treated the patient with intravenous hydrocortisone, levothyroxine, and liothyronine. After the treatment, she had no further episodes of torsades, and QTc improved to her baseline of 479 ms. Hypothyroidism is linked to electrocardiographic abnormalities such as sinus bradycardia, QT interval prolongation, malignant ventricular arrhythmias such as ventricular premature beat, ventricular tachycardia, TdP, and ventricular fibrillation. Assessment of thyroid function is of high value in QT prolongation syndromes to avoid SCD incidence. Thyroid hormone influences ventricular inhomogeneity, and L-thyroxine replacement treatment may minimize malignant ventricular arrhythmia and sudden cardiac death in patients with primary hypothyroidism. Our case highlights the importance of urgent electrolyte replacement and levothyroxine therapy to avoid the risk of ventricular arrhythmias.

While ectopic thyroid is an uncommon congenital condition, the occurrence of malignant transformation within ectopic lingual thyroid tissue is exceptionally atypical. We report a rare case of not otherwise specified (NOS) thyroid carcinoma (TC) arising in a sublingual ectopic thyroid in a 54-year-old male. The patient presented with progressive dysphonia, dysphagia, and upper airway obstruction, accompanied by severe hypothyroidism. Imaging studies, including ultrasonography, thyroid scintigraphy with technetium-99m pertechnetate, and cross-sectional computed tomography (CT), confirmed the absence of orthotopic thyroid tissue, identifying a highly vascularized sublingual tumor. Preoperative selective arterial embolization was performed to minimize intraoperative bleeding, followed by a successful surgical excision of the described mass. Histopathological analysis revealed NOS carcinoma arising in ectopic lingual thyroid tissue. The patient was subsequently maintained on suppressive Levothyroxine therapy and referred for radioiodine treatment. This case highlights the importance of a multidisciplinary diagnostic and therapeutic approach in the treatment of ectopic lingual TC. To our knowledge this is one of the few cases of NOS TC arising in a lingual thyroid gland.

22nd chromosome deletion syndrome (22q11.2 DS, del22q11.2) (with severe immunological disorders - Di Georg syndrome (SDH) or Di Giorgi syndrome (SDD)) It is one of the most common microdeletion syndromes.The disease is based on a violation of the formation of organs originating from the third gill arch.There is a full form of del22q11.2 syndrome with severe primary immunodeficiency (PID), congenital heart defects (CHD), hypoparathyroidism, facial skeletal abnormalities and high mortality during the first year of life, and partial forms without PID and calcium-phosphorus metabolism disorders.The high variability of clinical manifestations explains the fact that there are many different names of the disease in the literature: Di Giorgi syndrome (SDD), Di Georg syndrome (SDH), CATCH 22, velocardiofacial syndrome, Kyler syndrome, Sprintzen syndrome, facial and conotruncal abnormalities, etc.The term «Di Giorgi syndrome» is applicable to cases of deletion of 22q11.2 chromosome occurring with immune disorders. Despite the availability of genetic testing, many cases of 22q11.2 deletion syndrome remain undiagnosed due to its multsystem nature and varying severity of clinical manifestations, which is associated with a high risk of life-threatening complications.We present data from a 9-year-old patient with a partial form of deletion syndrome 22q11.2, when the reason for contacting an endocrinologist was the early appearance of secondary sexual characteristics against the background of decompensated primary hypothyroidism (Van Wyk-Grombach syndrome) in the absence of violations of phosphorus-calcium metabolism and PID.This clinical case demonstrates not only the variability of the clinical symptoms of the disease, but also the need for coordinated interaction of specialists from various specialties to diagnose polymorphic chromosomal pathology. Синдром делеции 22-й хромосомы (22q11.2 DS, del22q11.2) (при выраженных иммунологических нарушениях — синдром Ди Георга (СДГ), или синдром Ди Джорджи (СДД)) является одним из наиболее часто встречающихся микроделеционных синдромов. В основе заболевания лежит нарушение формирования органов, происходящих из третьей жаберной дуги. Различают полную форму синдрома del22q11.2 с тяжелым первичным иммунодефицитным состоянием (ПИД), врожденными пороками сердца (ВПС), гипопаратиреозом, аномалиями лицевого скелета и высокой летальностью в течение первого года жизни и частичные формы без ПИД и нарушений кальций-фосфорного обмена. Высокая вариабельность клинических проявлений объясняет тот факт, что в литературе имеется множество различных наименований заболевания: синдром Ди Джорджи (СДД), синдром Ди Георга (СДГ), CATCH 22, велокардиофасциальный синдром, синдром Кайлера, синдром Шпринтцена, синдром лицевых и конотрункальных аномалий и т.д. Термин «синдром Ди Джорджи» применим к случаям делеции 22q11.2 хромосомы, протекающими с иммунными нарушениями. Несмотря на доступность генетического тестирования, многие случаи синдрома делеции 22q11.2 остаются недиагностированными из-за его мультисистемного характера и различной выраженности клинических проявлений, что сопряжено с высоким риском развития жизнеугрожающих осложнений. Мы приводим данные пациентки 9 лет с частичной формой синдрома делеции 22q11.2, когда поводом для обращения к эндокринологу стало раннее появление вторичных половых признаков на фоне декомпенсированного первичного гипотиреоза (синдром Ван Вика-Громбаха) при отсутствии нарушений фосфорно-кальциевого обмена и ПИД. Представленный клинический случай демонстрирует не только вариабельность клинической симптоматики данного заболевания, но и необходимость слаженного взаимодействия специалистов различных специальностей для диагностики полиморфной хромосомной патологии.

Cantú syndrome involves fetal polyhydramniosis, congenital hypertrichosis, and macrosomia. Distinctive features include acromegaloid features with broad nasal bridge and macroglossia as well as cardiac abnormalities, including patent ductus arteriosus. We present a case in a male patient, who presented with cardiac abnormalities in childhood, but was diagnosed with the syndrome in adulthood after many years of atypical symptoms such as multiple endocrinopathies and infection susceptibility. He had surgery for a patent ductus arteriosus in early childhood. During adulthood, he developed idiopathic pericarditis. Extensive rheumatological investigations were made, and in parallel, several endocrinopathies were found. These included thyroiditis with subsequent hypothyroidism, idiopathic partial hypocortisolism, and GH insufficiency. In addition, he had mild neutropenia and required hospitalization twice because of Streptococcus pyogenes infections. Immunodeficiency screening has not revealed a specific primary immunodeficiency, yet transient neutropenia, low count of CD8+ effector memory T cells, as well as lymphocyte responses, was seen during bacteremia. The diagnose was made after a trio-whole genome sequencing identified a pathogenic missense variant of the gene ABCC9 (c.3460C > T;p. (Arg1154Trp)) causing Cantú syndrome.