title: Thyroid developmental anomalies in first degree relatives of children with congenital hypothyroidism.
abstract: Congenital hypothyroidism (CH) is most frequently caused by thyroid developmental abnormalities and it has recently been seen to have a familial component. The aim of this study was to investigate whether thyroid developmental abnormalities exist in first degree relatives of CH children with thyroid dysgenesis, an anomaly which, when present, is sometimes asymptomatic. Thyroid ultrasonography and function were evaluated among first degree relatives (n = 241) of 84 isolated CH children with thyroid dysgenesis. The results were compared with those of an unselected control population (n = 217). In 19 individuals (7.9% of cases) belonging to 18 families (21.4%), 21 cases of thyroid developmental abnormalities were detected, whereas only 2 subjects (0.9%) were affected in controls (P < 0.001). These 21 thyroid developmental abnormalities included thyroglossal duct cysts (n = 14), additional thyroid tissue with presence of a pyramidal lobe (n = 3), thyroid hemiagenesis (n = 3), and ectopic thyroid tissue (n = 1). All of these subjects showed normal thyroid function and belonged to nuclear families of CH children with athyreosis (n = 8), ectopic thyroid tissue (n = 9), or hemiagenesis (n = 1). A segregation analysis led to the conclusion that thyroid developmental abnormalities are compatible with an autosomal dominant mode of inheritance with a low penetrance estimated at 21% for asymptomatic thyroid developmental abnormalities and a probability of less than 7% of developing CH for a carrier of the susceptibility allele. In conclusion, these observations support the hypothesis of a common genetic component of the disorder with heterogeneous phenotypes.
authors.affiliation: Pediatric Endocrinology Unit and INSERM U457, Hôpital Robert Debré, 75019 Paris, France. juliane.leger@rdb.ap-hop-paris.fr
authors.forename: Juliane
authors.initials: J
authors.lastname: Léger
authors.forename: Daniella
authors.initials: D
authors.lastname: Marinovic
authors.forename: Catherine
authors.initials: C
authors.lastname: Garel
authors.forename: Catherine
authors.initials: C
authors.lastname: Bonaïti-Pellié
authors.forename: Michel
authors.initials: M
authors.lastname: Polak
authors.forename: Paul
authors.initials: P
authors.lastname: Czernichow
mesh_terms: D000328:Adult; D002828:Choristoma / Q000000981:diagnostic imaging / Q000235:genetics; D020090:Chromosome Segregation; D000013:Congenital Abnormalities / Q000000981:diagnostic imaging / Q000453:epidemiology / Q000235:genetics; D003409:Congenital Hypothyroidism; D005260:Female; D006801:Humans; D007037:Hypothyroidism / Q000235:genetics*; D015994:Incidence; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D011446:Prospective Studies; D011877:Radionuclide Imaging; D017678:Sex Distribution; D013955:Thyroglossal Cyst / Q000453:epidemiology; D013959:Thyroid Diseases / Q000000981:diagnostic imaging / Q000235:genetics*; D013961:Thyroid Gland / Q000002:abnormalities* / Q000000981:diagnostic imaging; D014463:Ultrasonography; D002577:Uterine Cervical Diseases / Q000000981:diagnostic imaging / Q000235:genetics