Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping ...Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping countries.Methods: A total of 312 first degree relativesbelonging to 80 families of children with TD (group 1)and 40 families of age-matched normal children (group2) were screened by thyroid ultrasonography, serum totalthyroxine (T4) and thyroid stimulating hormone (TSH).Results: Thyroid scintigraphy revealed agenesis in78.7% of the patients, ectopic gland in 15%, and hypoplasiain 6.2%. The mean thyroid volumes were similar in parentsand siblings of both groups. Eight (10.6%) mothers in group1 were identified to have thyroid hypoplasia as comparedwith none in group 2 (P=0.03). Serum TSH was signifi cantlyhigher in group 1 than in group 2 (P=0.004). Sixteen (7.8%)subjects (6 mothers, 5 fathers, and 5 siblings) in group 1were found to have subclinical hypothyroidism as comparedto none in group 2 (P<0.05). Four families were identifiedto have thyroid developmental anomalies and abnormalthyroid functions accounting for 5% of cases of familial TDin our cohort.Conclusions: Thyroid developmental anomalies andthyroid function abnormalities are more frequent in firstdegree relatives of children with TD as compared with acontrol population. These findings suggest that possiblythere is a genetic component of TD in Indian patients.展开更多
Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and one of the most common preventable causes of intellectual disability in the world. CH may be due to developmental or functional thyroid...Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and one of the most common preventable causes of intellectual disability in the world. CH may be due to developmental or functional thyroid defects (primary or peripheral CH) or be hypothalamic-pituitary in origin (central CH). In most cases, primary CH is caused by a developmental malformation of the gland (thyroid dysgenesis, TD) or by a defect in thyroid hormones synthesis (dyshormonogenesis, DH). TD represents about 65% of CH and a genetic cause is currently identified in fewer than 5% of patients. The remaining 35% are cases of DH and are explained with certainty at the molecular level in more than 50% of cases. The etiology of CH is mostly unknown and may include contributions from individual and environmental factors. In recent years, the detailed phenotypic description of patients, high-throughput sequencing technologies, and the use of animal models have made it possible to discover new genes involved in the development or function of the thyroid gland. This paper reviews all the genetic causes of CH. The modes by which CH is transmitted will also be discussed, including a new oligogenic model. CH is no longer simply a dominant disease for cases of CH due to TD and recessive for cases of CH due to DH, but a far more complex disorder.展开更多
文摘Background: Familial clustering in patients withpermanent congenital hypothyroidism (CH) caused bythyroid dysgenesis (TD) has been reported in developedcountries. There is no information on familial TD fromdeveloping countries.Methods: A total of 312 first degree relativesbelonging to 80 families of children with TD (group 1)and 40 families of age-matched normal children (group2) were screened by thyroid ultrasonography, serum totalthyroxine (T4) and thyroid stimulating hormone (TSH).Results: Thyroid scintigraphy revealed agenesis in78.7% of the patients, ectopic gland in 15%, and hypoplasiain 6.2%. The mean thyroid volumes were similar in parentsand siblings of both groups. Eight (10.6%) mothers in group1 were identified to have thyroid hypoplasia as comparedwith none in group 2 (P=0.03). Serum TSH was signifi cantlyhigher in group 1 than in group 2 (P=0.004). Sixteen (7.8%)subjects (6 mothers, 5 fathers, and 5 siblings) in group 1were found to have subclinical hypothyroidism as comparedto none in group 2 (P<0.05). Four families were identifiedto have thyroid developmental anomalies and abnormalthyroid functions accounting for 5% of cases of familial TDin our cohort.Conclusions: Thyroid developmental anomalies andthyroid function abnormalities are more frequent in firstdegree relatives of children with TD as compared with acontrol population. These findings suggest that possiblythere is a genetic component of TD in Indian patients.
基金Athanasia Stoupa received a research grant from the European Society for Paediatric Endocrinology (ESPE). Aurore Carré, Dulanjalee Kariyawasam, and Michel Polak received funding from Sandoz SAS and Merck Serono France, the French Society of Endocrinology and Paediatric Diabetology (SFEDP), and the French National Research Agency (ANR-21-CE14-0055-01-MITHY-PLA) .
文摘Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and one of the most common preventable causes of intellectual disability in the world. CH may be due to developmental or functional thyroid defects (primary or peripheral CH) or be hypothalamic-pituitary in origin (central CH). In most cases, primary CH is caused by a developmental malformation of the gland (thyroid dysgenesis, TD) or by a defect in thyroid hormones synthesis (dyshormonogenesis, DH). TD represents about 65% of CH and a genetic cause is currently identified in fewer than 5% of patients. The remaining 35% are cases of DH and are explained with certainty at the molecular level in more than 50% of cases. The etiology of CH is mostly unknown and may include contributions from individual and environmental factors. In recent years, the detailed phenotypic description of patients, high-throughput sequencing technologies, and the use of animal models have made it possible to discover new genes involved in the development or function of the thyroid gland. This paper reviews all the genetic causes of CH. The modes by which CH is transmitted will also be discussed, including a new oligogenic model. CH is no longer simply a dominant disease for cases of CH due to TD and recessive for cases of CH due to DH, but a far more complex disorder.
