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BackgroundChildren with familial dysautonomia (FD) are smaller and grow more slowly than the general population. It is unknown whether this abnormal growth is due to comorbidities that patients with FD live with, or if it is a direct effect of the disease-causing homozygous ELP-1 mutations. Here, we created growth curves for weight, height, and body mass index (BMI) in male and female children with FD to monitor the nutritional status of patients with FD.MethodsWe used the New York University (NYU) FD Registry which includes data from 680 individuals with FD who were followed longitudinally since birth. We generated sex-specific FD growth charts for three age ranges (birth to 36 months, 2 to 20 years, and 2 to 40 years) and compared them to the general population. We generated Kaplan-Meier curves to test the hypothesis that FD patients with low BMI had shorter survival than the rest of the cohort.ResultsGrowth charts generated from 591 individuals with FD show that these patients grow more slowly, reach less height, and gain less weight than the general population. The impact of FD on height was more pronounced in girls than in boys. However, both groups showed markedly low weights, which resulted in low BMI. Low weight, but not height, is already evident at birth. In a subpopulation of FD patients, we found that treatment with growth hormone or spinal fusion surgery helped patients achieve the expected growth characteristic of FD patients, but these treatments did not lead FD patients to achieve the growth pattern of the general population. Contrary to our hypothesis, low BMI had no impact on patient survival.ConclusionsPediatric patients with FD have lower height, weight, and BMI compared to the general pediatric population, but this does not appear to affect survival. Growth curves specific to the FD population are an important tool to monitor growth and nutritional status in pediatric patients with FD when the general population growth curves are of limited use.</div

Growth Hormone treatment in male patients with FD.

Growth velocity (GV in cm/year) of male FD patients one year before and 1–5 years after treatment start. Height 1 indicates the height around 20 years of age or the closest value. Height 2 indicates the height at 30 years of age or closest value. n/a, not applicable (patient too young and/or still alive); unk, unknown (missing data); *, spine fusion surgery. (DOCX)</p

Growth, length, and weight of babies with familial dysautonomia (FD) at birth compared to the general population.

A. Growth plots in patients with FD 0–36 months old. Selected smoothed weight (top) and height (bottom) percentiles for female and male babies with FD. B. Length (cm) and weight (kg) of patients with FD at birth compared to the mean at birth of the general population (CDC). Each dot represents one FD patient. The red line indicates the mean weight (top) and length (bottom) at birth of FD baby girls; blue line indicates the mean weight (top) and length (bottom) at birth of FD baby boys. Mean values for healthy baby girls and boys of the general population are indicated by a black line in all plots. P-values are indicated in the right top corner of every graph. N = 143 (FD boys); N = 144 (FD girls) for length; N = 221 (FD boys); N = 258 (FD girls) for weight. For the birth values of the general population, number of subjects is N = 893 for boys and N = 843 for girls for both length and weight [14].</p

Growth curves for familial dysautonomia FD patients who received growth hormone treatment.

Selected smoothed height graphs percentiles for female and male individuals with FD that received GH treatment (color lines; N = 20 males; N = 14 females) compared to FD patients with no GH treatment (black lines; N = 140 males; N = 132 females).</p

Growth demographics in patients with FD at or around age 25 and healthy subjects in the 50^th percentile at age 20 (CDC).

Growth demographics in patients with FD at or around age 25 and healthy subjects in the 50th percentile at age 20 (CDC).</p

Growth, height and weight in patients with FD that underwent spinal fusion surgery.

Growth, height and weight in patients with FD that underwent spinal fusion surgery.</p

Impact of body mass index and weight at birth on survival in patients with familial dysautonomia (FD).

Cumulative probability of survival in patients with FD with normal BMI vs patients with FD with low BMI at age 20 in females (A) and males (B). Cumulative probability of survival in patients with FD with weight at birth at or above average vs patients with FD with weight below average in females (C) and males (D). Cumulative probability of survival in patients with FD with weight at birth at or above 1 SD of the average vs patients with FD with weight below 1 SD of the average in females (E) and males (F).</p

Growth Hormone treatment in female patients with FD.

Growth velocity (GV in cm/year) of female FD patients one year before and 1–5 years after treatment start. Height 1 indicates the height around 20 years of age or the closest value. Height 2 indicates the height at 30 years of age or closest value. n/a, not applicable (patient too young and/or still alive); unk, unknown (missing data); *, spine fusion surgery. (DOCX)</p

Weight, stature, and body mass index (BMI) for age in patients with familial dysautonomia (FD) aged 2–20 years old.

Selected smoothed percentiles. Red plots (A, C, E) denote females (n = 301), blue plots (B, D, F) denote males (n = 290), and black plots (all panels) represent CDC reference charts for the general population.</p

Growth demographics in patients with FD.

BackgroundChildren with familial dysautonomia (FD) are smaller and grow more slowly than the general population. It is unknown whether this abnormal growth is due to comorbidities that patients with FD live with, or if it is a direct effect of the disease-causing homozygous ELP-1 mutations. Here, we created growth curves for weight, height, and body mass index (BMI) in male and female children with FD to monitor the nutritional status of patients with FD.MethodsWe used the New York University (NYU) FD Registry which includes data from 680 individuals with FD who were followed longitudinally since birth. We generated sex-specific FD growth charts for three age ranges (birth to 36 months, 2 to 20 years, and 2 to 40 years) and compared them to the general population. We generated Kaplan-Meier curves to test the hypothesis that FD patients with low BMI had shorter survival than the rest of the cohort.ResultsGrowth charts generated from 591 individuals with FD show that these patients grow more slowly, reach less height, and gain less weight than the general population. The impact of FD on height was more pronounced in girls than in boys. However, both groups showed markedly low weights, which resulted in low BMI. Low weight, but not height, is already evident at birth. In a subpopulation of FD patients, we found that treatment with growth hormone or spinal fusion surgery helped patients achieve the expected growth characteristic of FD patients, but these treatments did not lead FD patients to achieve the growth pattern of the general population. Contrary to our hypothesis, low BMI had no impact on patient survival.ConclusionsPediatric patients with FD have lower height, weight, and BMI compared to the general pediatric population, but this does not appear to affect survival. Growth curves specific to the FD population are an important tool to monitor growth and nutritional status in pediatric patients with FD when the general population growth curves are of limited use.</div