Mean Standard Deviation Score For Height Research Articles

Obesity-Associated GNAS Mutations and the Melanocortin Pathway

BackgroundGNAS encodes the Gαs (stimulatory G-protein alpha subunit) protein, which mediates G protein–coupled receptor (GPCR) signaling. GNAS mutations cause developmental delay, short stature, and skeletal abnormalities in a syndrome called Albright’s hereditary osteodystrophy. Because of imprinting, mutations on the maternal allele also cause obesity and hormone resistance (pseudohypoparathyroidism).MethodsWe performed exome sequencing and targeted resequencing in 2548 children who presented with severe obesity, and we unexpectedly identified 22 GNAS mutation carriers. We investigated whether the effect of GNAS mutations on melanocortin 4 receptor (MC4R) signaling explains the obesity and whether the variable clinical spectrum in patients might be explained by the results of molecular assays.ResultsAlmost all GNAS mutations impaired MC4R signaling. A total of 6 of 11 patients who were 12 to 18 years of age had reduced growth. In these patients, mutations disrupted growth hormone–releasing hormone receptor signaling, but growth was unaffected in carriers of mutations that did not affect this signaling pathway (mean standard-deviation score for height, −0.90 vs. 0.75, respectively; P=0.02). Only 1 of 10 patients who reached final height before or during the study had short stature. GNAS mutations that impaired thyrotropin receptor signaling were associated with developmental delay and with higher thyrotropin levels (mean [±SD], 8.4±4.7 mIU per liter) than those in 340 severely obese children who did not have GNAS mutations (3.9±2.6 mIU per liter; P=0.004).ConclusionsBecause pathogenic mutations may manifest with obesity alone, screening of children with severe obesity for GNAS deficiency may allow early diagnosis, improving clinical outcomes, and melanocortin agonists may aid in weight loss. GNAS mutations that are identified by means of unbiased genetic testing differentially affect GPCR signaling pathways that contribute to clinical heterogeneity. Monogenic diseases are clinically more variable than their classic descriptions suggest. (Funded by Wellcome and others.)

The effect of growth hormone treatment on height in children with idiopathic short stature.

Idiopathic short stature (ISS) is short stature of unknown cause. In 2003, the Food and Drug Administration (FDA) approved the use of growth hormone (GH) for ISS. Several studies have evaluated the effect of GH in children with ISS, in whom improved growth velocities and height standard deviation scores (SDS) have been reported. However, clinical variables influence the height improvement. This study aimed to evaluate the effects of GH treatment on ISS and to analyze clinical factors associated with growth velocity. This study was conducted retrospectively. Subjects diagnosed with ISS at Ajou University Hospital were divided into two groups, an ISS with GH-treatment group (n=34) and an ISS control group (n=36). All children were prepubertal, and aged <10 years. We reviewed their auxological data, laboratory findings, and bone age. Growth velocity of the GH-treatment group exceeded that of controls by 3.37 cm/year (95% CI, 2.78-3.95). At baseline, the mean SDS for height in the treatment and control groups were equivalent (-2.25 ± 0.29 and -2.22 ± 0.31, respectively). However, after 1 year, the height of the GH-treated group exceeded that of the control group by 0.73 SDS (95% CI, 0.57-0.88). A negative correlation was found between age and growth velocity in the GH-treatment group. GH treatment increased short-term growth velocity and height SDS of Korean children with ISS. Age was identified as the single most important factor correlated with growth velocity in GH treatment.

Association of adverse perinatal events with an empty sella turcica in children with growth hormone deficiency.

High-resolution computed tomography (HR-CT) of the hypothalamo-pituitary region was performed in 26 consecutive children presenting with growth hormone deficiency (GHD) at one clinic. 58% had an empty sella turcica (ES) and 42% a full sella turcica (FS). There was no difference between the ES and FS groups for mean (+/- 95% confidence limits) presentation age (ES 6.7 (+/- 1.8) years, FS 5.6 (+/- 2.2) years), height standard deviation score (SDS) (ES -3.9 (+/- 0.8), FS -3.3 (+/- 0.5] nor head circumference SDS (ES -1.9 (+/- 1.1), FS -0.7 (+/- 1.1]. There were significant associations between the ES group and a history of adverse perinatal events (p less than 0.001) and multiple pituitary deficiency (p = 0.014). Growth hormone response to an acute growth hormone releasing factor test showed no association with HR-CT diagnosis. Sella turcica volumes were calculated from the HR-CT scans. All sella volumes were small; mean SDS for height was -2.6 (+/- 0.2). There was no difference in sella volume SDS between the ES and FS groups (ES -2.9 (+/- 0.3), FS -2.5 (+/- 0.4]. Adverse perinatal events may cause an ES and GHD by compromising the blood supply to the pituitary gland or infundibulum.

CATCH UP GROWTH AND CHILD ABUSE

Poor growth in association with child abuse is well recognised but eventual outcome in terms of growth parameters has not been clearly defined. The changes in standard deviation scores (SDS) for height and weight were calculated in 95 children who had suffered child abuse. Catch up growth was defined as an increase in SDS >1.0. Ages at presentation ranged from 6 weeks to 12 years and length of follow up from 9 months to 8 years. The mean SDS for height and weight increased significantly between presentation and most recent clinic visit (p <0.001 and p <0.01 respectively). The 64 children who remained at home (group 1) showed a significant increase in height SDS only (p <0.01). The 20 children taken into long term fostercare or adopted (group 2) showed significant increases in both height and weight SDS (p <0.001 and p <0.01 respectively). The remaining 11 children who were fostered for short periods only (group 3) showed little change in either index. Catch up growth in height occurred in 12% of group 1 compared to 55% group 2 (p <0.001). Catch up growth in weight occurred in 22% group 1 compared to 50% group 2 (p <0.05). Children suffering child abuse show greater catch up growth when taken into long term care.