Long-term auxological and endocrinological evaluation of patients with 9p trisomy: a focus on the growth hormone-insulin-like growth factor-I axis

Abstract

BackgroundTrisomy 9p is an uncommon anomaly characterised by mental retardation, head and facial abnormalities, congenital heart defects, kidney abnormalities, and skeletal malformations. Affected children may also show growth and puberty retardation with delayed bone age. Auxological and endocrinological data are lacking for this syndrome.MethodsWe describe three girls and one boy with 9p trisomy showing substantial growth failure, and we evaluate the main causes of their short stature.ResultsThe target height was normal in all families, ranging from 0.1 and -1.2 standard deviation scores (SDS). The patients had a low birth-weight (from -1.2 to -2.4 SDS), birth length (from -1.1 to -3.2 SDS), and head circumference (from -0.5 to -1.6 SDS). All patients presented with substantial growth (height) retardation at the time of 9p trisomy diagnosis (from -3.0 to -3.8 SDS).The growth hormone stimulation test revealed a classic growth hormone (GH) deficiency (GHD) in patients 1, 3, and 4. In contrast, patient 2 was determined to have a GH neurosecretory dysfunction (GHNSD). The plasma concentrations of IGF-I and IGFBP-3 were low in all patients for their ages and sexes (from -2.0 to -3.4 SDS, and from -1.9 to -2.8 SDS, respectively).The auxological follow-up showed that those patients who underwent rhGH treatment exhibited a very good response to the GH therapy, whereas patients 3 and 4, whose families chose not to use rhGH treatment, did not experience any significant catch-up growth.ConclusionsGH deficiency appears to be a possible feature of patients with 9p trisomy syndrome. These patients, particularly those with growth delays, should be evaluated for GH secretion.

Characterization of a Complex Chromosomal Rearrangement Involving a de novo Duplication of 9p and 9q and a Deletion of 9q

“…Previous studies have found that dup(9p) could be the result of the recombination events between homologous repeats in this region [Krepischi and Vianna, 2003]. Clinical severity in trisomy 9p generally correlates with the extent of the trisomic chromosome region; duplication of 9pterp11 is associated with milder dysmorphism, whereas duplication of 9p21.1q22-32 is associated with more severe craniofacial features [Stagi et al, 2014]. It seems that the 9p22 region is responsible for the principal phenotype observed in dup(9p) [Haddad et al, 1996].…”

“…Partial duplication of 9p is one of the most commonly detected autosomal structural abnormalities in liveborn infants [Di Bartolo et al, 2012;Stagi et al, 2014]. In most cases, it is due to different types of translocations.…”

“…congenital heart defects, central nervous system affection, kidney anomalies, and skeletal malformations [Stagi et al, 2014].…”

Trisomy 9p. A brief clinical, diagnostic and therapeutic description

“…1 A potential explanation may be that this is a relatively poor gene region, so it may be more compatible with survival. [1][2][3] Trisomy 9p accounts for the fourth most frequent autosomal trisomy, after trisomies 21, 18, and 13. 2,4 It was first described in 4 patients by Rethoré et al in 1970 [1][2][3][4][5] and then outlined by Centerwall and Beatty-DeSana in 1975.…”

“…4 It is a clinically recognizable entity and, to date, more than 200 cases have been reported in the bibliography. [1][2][3][4][5][6] It is characterized by the complete (Figure 1) or partial duplication of 9p. 2 Treatment with recombinant human growth hormone may be considered in patients with trisomy 9p with short stature, while taking into account the severity of intellectual disability and the potential for social inclusion.…”