Growth trajectory and pubertal tempo from birth till final height in a girl with Wolf-Hirschhorn syndrome.

Growth anomaly is a prominent feature in Wolf-Hirschhorn syndrome (WHS), a rare congenital disorder caused by variable deletion of chromosome 4p. While growth charts have been developed for WHS patients 0–4 years of age and growth data available for Japanese WHS patients 0–17 years, information on pubertal growth and final height among WHS children remain lacking. Growth hormone (GH) therapy has been reported in two GH-sufficient children with WHS, allowing for pre-puberty catch up growth; however, pubertal growth and final height information was also unavailable. We describe the complete growth journey of a GH-sufficient girl with WHS from birth until final height (FH), in relation to her mid parental height (MPH) and target range (TR). Her growth trajectory and pubertal changes during childhood, when she was treated with growth hormone (GH) from 3 years 8 months old till 6 months post-menarche at age 11 years was fully detailed. Learning points: Pubertal growth characteristics and FH information in WHS is lacking. While pre-pubertal growth may be improved by GH, GH therapy may not translate to improvement in FH in WHS patients. Longitudinal growth, puberty and FH data of more WHS patients may improve the understanding of growth in its various phases (infancy/childhood/puberty). Background Wolf-Hirschhorn syndrome (1, 2, 3, 4) (WHS) is a rare congenital disorder caused by variable deletion of the short arm of chromosome 4 (2, 5). Considered a contiguous gene syndrome (4), multiple phenotypic features of variable degree have been described in individuals depending on the extent of deletion. These include developmental delay, skeletal anomalies, hearing loss, cardiac, neurological and urinary tract abnormalities. Growth anomalies are present in 80% of affected individual (4) and include prenatal-onset growth failure, short stature and poor weight gain, although normal stature is possible in mild phenotypes. To depict growth patterns from 0 to 4 years of age, growth charts were developed using data from 101 patients from Netherlands, Great Britain, North America, Germany and Australia (6). Among Asians, growth of 34 WHS Japanese children 0–17 years were collated and plotted against local norms (7). Both data sets, as well as data from other case reports (8, 9), describe marked growth retardation among children with WHS. However, information on pubertal growth and final height (FH) among WHS children was lacking. Growth hormone (GH) therapy was used in two GH-sufficient children with WHS, allowing pre-puberty catch up growth (9); however, pubertal growth and FH information was unavailable. We describe the complete growth journey of a girl with WHS from birth until FH, in relation to her mid parental height (MPH) and target range (TR). We also describe her growth trajectory and pubertal changes during childhood, when she was treated with GH from 3 years 8 months old till 6 months post menarche at age 11 years. The advantage of our report is the detailed capture of all important information to characterize the growth and pubertal changes, until FH.