Growth references for Japanese individuals with Noonan syndrome

Abstract

Background: Noonan syndrome (NS) is a clinically and genetically heterogeneous syndrome characterized by distinctive facial features, short stature, congenital heart diseases, and other comorbidities. NS-specific growth charts are essential for NS care, but currently no such charts are available for Asian populations. Methods:We conducted a nationwide survey by collaborating with three academic societies in Japan. We obtained the data of 356 clinically diagnosed NS subjects from 20 hospitals. The Lambda-Mu-Sigma method was used for establishing growth charts. results: A total of 308 subjects (males: 159 and females: 149) were analyzed after excluding 48 subjects because of missing auxological data (26 subjects), presence of complications affecting growth (5 subjects), and extreme longitudinal growth aberrations which lay more than three standard deviation scores from the mean in this population (17 subjects). Genetic analyses were performed in 150 patients (48.7%); 103 (68.7%) were reported to have some abnormalities in the known causative genes. Cardiovascular diseases were found in 256 patients (83.1%). The NS-specific height, weight, and BMI charts were constructed with 3,249 mixed longitudinal and cross-sectional measurements. conclusion: Growth standards for Japanese individuals with NS were established. These charts are expected to be used in various clinical settings.

Efficacy and safety of two doses of Norditropin^® (somatropin) in short stature due to Noonan syndrome: a 2-year randomized, double-blind, multicenter trial in Japanese patients

“…Change in height SDS from baseline to 104 weeks of treatment, based on the reference data for Japanese individuals with Noonan syndrome [8], was a supportive secondary endpoint. Secondary efficacy endpoints were height velocity SDS and height velocity from baseline to 52 weeks of treatment and from 52 weeks to 104 weeks of treatment.…”

“…BMI and BMI SDS were derived using height and body weight, and BMI SDS was provided only for baseline. Height SDS values were derived using the Japanese national reference data and also the reference data for Japanese individuals with Noonan syndrome (subsequently referred to as the 'Japanese Noonan syndrome reference data') [8]. All blood and urine samples were analyzed at a central laboratory.…”

“…gressive growth failure in infancy, sustained growth in childhood (below -2 standard deviation scores [SDS] of the growth curve of normal children), delayed growth spurt in puberty, and short stature in adulthood (just below -2 SDS) [1,[6][7][8][9].…”

First‐year growth in children with Noonan syndrome: Associated with feeding problems?

“…Growth has been investigated thoroughly in Noonan syndrome (Cessans et al, ; Isojima et al, ; Malaquias et al, ; Mendez & Opitz, ; Nora et al, ; Otten & Noordam, ; Ranke et al, ; Sharland et al, ; Shaw, Kalidas, Crosby, Jeffery, & Patton, ; Witt, Keena, Hall, & Allanson, ). Birth weight and birth length are usually normal or slightly subnormal.…”

“…Three studies have hypothesized an association between stunted growth in the first year of life and feeding problems in Noonan syndrome (Digilio et al, ; Isojima et al, ; Otten & Noordam, ), but this has never been investigated. Therefore, it remains unclear what the association is between feeding problems and growth in the first year of life.…”