Growth in achondroplasia including stature, weight, weight-for-height and head circumference from CLARITY: achondroplasia natural history study-a multi-center retrospective cohort study of achondroplasia in the US

Abstract

Background: Achondroplasia is the most common genetic skeletal disorder causing disproportionate short stature/dwarfism. Common additional features include spinal stenosis, midface retrusion, macrocephaly and a generalized spondylometaphyseal dysplasia which manifest as spinal cord compression, sleep disordered breathing, delayed motor skill acquisition and genu varus with musculoskeletal pain. To better understand the interactions and health outcomes of these potential complications, we embarked on a multi-center, natural history study entitled CLARITY (achondroplasia natural history study). One of the CLARITY objectives was to develop growth curves (length/height, weight, head circumference, weight-for-height) and corresponding reference tables of mean and standard deviations at 1 month increments from birth through 18 years for clinical use and research for achondroplasia patients.

Methods: All available retrospective anthropometry data including length/height, weight and head circumference from achondroplasia patients were collected at 4 US skeletal dysplasia centers (Johns Hopkins University, AI DuPont Hospital for Children, McGovern Medical School University of Texas Health, University of Wisconsin School of Medicine and Public Health). Weight-for-age values beyond 3 SD above the mean were excluded from the weight-for-height and weight-for-age curves to create a stricter tool for weight assessment in this population.

Results: Over 37,000 length/height, weight and head circumference measures from 1374 patients with achondroplasia from birth through 75 years of age were compiled in a REDCap database. Stature and weight data from birth through 18 years of age and head circumference from birth through 5 years of age were utilized to construct new length/height-for-age, weight-for-age, head circumference-for-age and weight-for-height curves.

Conclusion: Achondroplasia-specific growth curves are essential for clinical care of growing infants and children with this condition. In an effort to provide prescriptive, rather than purely descriptive, references for weight in this population, extreme weight values were omitted from the weight-for-age and weight-for-height curves. This well-phenotyped cohort may be studied with other global achondroplasia populations (e.g. Europe, Argentina, Australia, Japan) to gain further insight into environmental or ethnic influences on growth.

Keywords: Achondroplasia; Anthropometry; Head circumference; Height/length; Weight.

Fig. 1

Description of subjects and criteria to include anthropometry in height/length-, weight- and head circumference-for-age and weight-for-age curves

Fig. 2

Stature-for-age for males with achondroplasia, 5th, 25th, 50th, 75th and 95th percentiles. Birth—36 months (top) derived from 3024 data points from 544 subjects and birth—18 years (bottom) derived from 4011 data points from 549 subjects

Fig. 3

Stature-for-age for females with achondroplasia, 5th, 25th, 50th, 75th and 95th percentiles. Birth—36 months (top) derived from 2700 data points from 489 subjects and birth—18 years (bottom) derived from 3703 data points from 502 subjects

Fig. 4

Weight-for-age for males with achondroplasia, 5th, 25th, 50th, 75th and 95th percentiles. Birth—36 months (top) derived from 3585 data points from 549 subjects and birth—18 years (bottom) derived from 4512 data points from 528 subjects

Fig. 5

Weight-for-age for females with achondroplasia, 5th, 25th, 50th, 75th and 95th percentiles. Birth—36 months (top) derived from 3087 data points from 491 subjects and birth—18 years (bottom) derived from 4236 data points from 482 subjects

Fig. 6

a–d Weight-for-height curves for males a ≥ 50 cm and < 80 cm including 2822 data points from 493 subjects and males b > 80 cm and < 110 cm including 2180 data points from 413 subjects; Weight-for-height curves for males c > 110 cm and < 140 cm including 956 data points from 265 subjects and d by age category

Fig. 6

a–d Weight-for-height curves for males a ≥ 50 cm and < 80 cm including 2822 data points from 493 subjects and males b > 80 cm and < 110 cm including 2180 data points from 413 subjects; Weight-for-height curves for males c > 110 cm and < 140 cm including 956 data points from 265 subjects and d by age category

Fig. 7

a–d Weight-for-height curves for females a ≥ 50 cm and ≤ 80 cm including 2478 data points from 440 subjects and females b > 80 cm and ≤ 110 cm including 2420 data points from 388 subjects.; Weight-for-height curves for females c ≥ 110 cm and ≤ 140 cm including 952 data points from 263 subjects and d by age category

Fig. 7

a–d Weight-for-height curves for females a ≥ 50 cm and ≤ 80 cm including 2478 data points from 440 subjects and females b > 80 cm and ≤ 110 cm including 2420 data points from 388 subjects.; Weight-for-height curves for females c ≥ 110 cm and ≤ 140 cm including 952 data points from 263 subjects and d by age category

Fig. 8

Head circumference-for-age from birth through 5 years for children with achondroplasia, 5th, 25th, 50th, 75th and 95th percentiles. Male curve (top) derived from 3449 data points from 534 subjects and female curve (bottom) derived from 3012 data points from 489 subjects. These figures include data points from subjects who underwent shunt placement and cervicomedullary decompression (CMD) (from before and after the procedures). There was no difference in the male or female head circumference-for-age curves when the data points from these subjects were excluded. For males, there were 361 data points from 49 subjects who had a shunt (196 data points after the surgery) and 825 data points from 116 subjects who had CMD (462 data points after the surgery). For females, there were 197 data points from 99 subjects (116 data points after the surgery) and 757 data points from 122 subjects who had CMD (374 data points after the surgery). This figures include data points from subjects who underwent shunt placement and CMD (from before and after the procedures). There was no difference in the male or female head circumference-for-age curve when the data points from these subjects were excluded. For males, there were 361 data points from 49 subjects who had a shunt (196 data points after the surgery) and 825 data points from 116 subjects who had CMD (462 data points after the surgery). For females, there were 197 data points from 99 subjects (116 data points after the surgery) and 757 data points from 122 subjects who had CMD (374 data points after the surgery)