Epidemiology of disorders associated with tall stature in childhood: A 20-year birth cohort study

Abstract

Many primary and secondary disorders in childhood may cause tall stature (height of +2 standard deviations above the mean height for age and sex). Growth-monitoring programs are aimed at early detection of such disorders to avoid permanent health consequences and support children's wellbeing. However, age- and sex-specific data on the incidence of disorders associated with tall stature are scarce. This retrospective population-based cohort study aims to specify the epidemiological data that are needed to develop better diagnostic practices. The study population included 1 144 503 children (51% boys) born in Finland between 1998 and 2017 with 16.5 million register notifications including medical diagnoses. The first occurrences of several primary or secondary disorders associated with tall stature were identified from multiple registers. The age- and sex-specific cumulative incidences (CMIs) from birth until 18 years of age and the median age at diagnosis were determined. A total of 1641 children (0.14% of the whole birth cohort, 44% boys) had a primary or secondary disorder associated with tall stature. Klinefelter syndrome (47,XXY karyotype) was the most common primary disorder (median age at diagnosis: 8.4 years, CMI at 18 years: 1/2146 boys). Marfan syndrome (5.9 years, 1/4307 girls; 7.1 years, 1/5202 boys) and congenital overgrowth syndromes (1.7 years, 1/4717 girls; 1.8 years; 1/4925 boys) did not have a predilection for either sex. Secondary conditions such as central precocious puberty (1/894 girls at 8 years, and 1/4856 boys at 9 years) and hyperthyroidism (15.1 years, 1/936 girls; 14.4 years, 1/5675 boys) were more common among girls. Disorders associated with tall stature are rare and are frequently underdiagnosed in childhood. We suggest that during early childhood, the focus of growth screening should be particularly on Marfan syndrome and congenital overgrowth syndromes, with the addition of Klinefelter syndrome and central precocious puberty thereafter.

Fig 1. Cumulative incidence of Klinefelter syndrome, 47,XYY syndrome, triple X syndrome, and Fragile X syndrome from birth to 18 years of age.

Fig 2. Cumulative incidence of congenital overgrowth syndromes, Marfan syndrome, and congenital adrenal hyperplasia from birth to 18 years of age.