Growth in CHARGE syndrome: optimizing care with a multidisciplinary approach

Figures & data

Figure 1 Flow chart of publication selection. Entry terms: CHARGE syndrome, CHARGE association, Hall Hittner syndrome, Hall Hittner association, growth, body size, weight, height, body mass, BMI, length, birth weight, head circumference, short stature, birth size, morphometry, anthropometry, puberty, hypogonadism, Kallmann, adolescent and adolescence. MeSH terms for PubMED search: CHARGE syndrome, Body weights and measures, growth and development, puberty, delayed puberty and hypogonadism. Emtree terms for Embase search: syndrome CHARGE, morphometry and growth, development and aging.

Abbreviations: CHARGE, coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital hypoplasia, ear anomalies including hearing loss. BMI, body mass index.

Table 1 Growth data from literature

Author, year	Study type	Prenatal/at birth	0–3 years	3–12 years	12–18 years	18+	No specified age group
Aguiar-Oliveira, 2017^Citation22	Case-report	Born at term (40 weeks) US: normal intrauterine growth BL 46cm, BW 2.9kg, both below 3rd percentile
Aramaki, 2006^Citation21	Cohort study. 17 children with CHARGE syndrome and CHD7 mutation (5 mo–18 yrs).	BL & BW: SGA?	H range (n=5) -4.4/-5.6SD W range (n=5) -2.6/-5.9SD Age range 5 mo–2 y 6 mo	H range (n=8) -1.5/-6.0SD W range (n=8) -0.7/-4.7SD Age range 3 y–6 y 5 mo	H range (n=3) -2.9/-7.1SD W range (n=3) -1.5/-3.6SD Age range 12 y–18 y	H (n=1) −2.5SD W (n=1) −0.7SD
Asakura, 2008^Citation23	Cohort study. 8 children with CHARGE syndrome and CHD7 mutation.	Average BL −1.9SD		H <−2SD in all cases Age range 0.9–11.0 y 1 patient 0.9 y; rest 5.8–11.0 y
Blake, 2005^Citation14	Cohort study. 30 adults and adolescents with CHARGE syndrome.					Male (n=5) mean H 167.5 Female (n=6) mean H 161cm
Blake, 1993^Citation24	Cohort study. 44 children 0.5–18 y	Mean BW & BL on or above 50th percentile	Mean W & H for boys and girls <3rd percentile. Catch-up growth in preschool years
Dauber, 2010^Citation25	Case report	BW  ~ 50th percentile BL 25th–50th percentile	H <5th percentile from 2 y		15 y H −3.1SD W −1.4SD
Dörr, 2015^Citation26	Cohort study. 19 patients (9f; 10m)	Median BW −0.78SD BL −0.5SD	3–4 weeks median H −2.36 1 y median H −2.52SD Median BMI −1.15SD	5 y median H −2.8 Median BMI −0.15SD
Forward, 2007^Citation31	Cohort study. 30 patients (15m;15f) 13–34 y						H 30% 10th–25th percentile; 56% <5th percentile. 11% overweight; 74% normal weight; 15% underweight.
Harvey, 1991^Citation27	Cohort study. 17 patients, 7 survivors	3/17 SGA	Failure to thrive in 7/7 patients. 4/7 catch-up growth after 1–2 years.
Husu, 2012^Citation15	Cohort study. 18 patients (15 growth data)						H ≤ −2.5SD in 9/15 (60%) of patients
Jain, 2011^Citation42	Case-report	Premature birth (25 weeks) BW 795 g				18 y H −3.58SD
Jongmans, 2006^Citation6	Cohort study. 2days–40 years						63% (21/32) H <3rd percentile
Khadilkar, 1999^Citation30	Cohort study. 4 children with CHARGE (3M; 1F)		H (n=1) −3.0SD	H range (n=3) -2.7SD/-4.3SD
Legendre, 2012^Citation29	Retrospective case series. 40 fetuses with CHD7 mutation	No IUGR
Legendre, 2017^Citation7	Cohort study. 119 patients with CHARGE syndrome (90% typical CHARGE)	Mean gestation at birth 36.6 weeks Mean BW −0.6SD Mean BL −1.3SD IUGR in 26% of cases					Mean H -1.7SD Mean W -0.9SD
Pinto, 2005^Citation18	Cohort study. 32 patients with CHARGE (20M; 12F)	34% SGA	Median H (n=25) -1.5SD at 1 y Median H (n=25) -1.5SD at 2 y	Median H (n=25) -2SD at 5 y Median H (n=9) -2.4SD
Searle, 2005^Citation28	Case-report. m patient with CHARGE from birth to 33 y	Normal size at birth	11 months W <3rd percentile	3 y: W 5th percentile H 10th percentile			Adult height 173.5 cm BMI 34.5
Shoji, 2011^Citation16	Cohort study. 25 patients with CHARGE		H range (n=3) -4.2/-3.2SD W range (n=3) -4.2/-2.3SD	H range (n=12) -5.4/-0.2SD W range (n=10) -3.3/0SD	H range (n=5) -4.8/-2.5SD W range (n=5) -2.8/-0.2SD	H range (n=5) -8.7/-1SD W range (n=5) -5/0.1SD	Mean H in m (n=12) -3.04SD Mean H in f (n=10) -3.64SD

Abbreviations: US, ultrasound; BL, birth length; BW, birth weight; H, height; W, weight; SGA, small for gestational age; y, year/s; mo, months; IUGR, intra uterine growth retardation; m, male; f, female; CHARGE, coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital hypoplasia, ear anomalies including hearing loss.

Table 2 Expert-based advice for multidisciplinary approach/guidance of medical problems in CHARGE syndrome

Growth-related issues	0–3 years	4–12 years	13–17 years	18+	Professionals involved
Monitoring of growth	Height, weight, head circumference	Height, weight	Height, weight	Weight	Pediatrician General practitioner
Feeding difficulties
Problems with sucking, chewing or swallowing	Choanal atresia Cleft lip/palate Cranial nerve abnormalities Vascular ring	Cranial nerve abnormalities Vascular ring Dental problems	Cranial nerve abnormalities Vascular ring Dental problems	Cranial nerve abnormalities Dental problems	Speech and language therapist Pediatrician/(pediatric) neurologist Ear nose throat specialist Dentist Plastic surgeon (Pediatric) cardiologist (vascular ring)
Aberrant feeding behavior	Functional, sensory and psychological evaluation.	Functional, sensory and psychological evaluation. Think of: Sensory problems, intellectual disability, feeding experiences in the past.	Functional, sensory and psychological evaluation.		Speech and language therapist Pediatrician Psychologist Intellectual disability physician (Netherlands)
Gastro-intestinal problems	Evaluation with special attention to: reflux, constipation, abdominal migraine.	Evaluation with special attention to: reflux, constipation, abdominal migraine.	Evaluation with special attention to: reflux, constipation, abdominal migraine.	Evaluation with special attention to: reflux, constipation, abdominal migraine.	Pediatrician/(pediatric) gastroenterologist Intellectual disability physician (Netherlands)
Chronic/critical disease
Cardiovascular problems	Combine surgeries and hospital admissions. Consider enriched diet/tube feeding.	Combine surgeries and hospital admissions. Consider enriched diet/tube feeding.	Combine surgeries and hospital admissions. Consider enriched diet/tube feeding.		Pediatric cardiologist Pediatrician Dietician
Multiple surgeries and/or hospital admissions	Combine surgeries and hospital admissions. Consider enriched diet/tube feeding.	Combine surgeries and hospital admissions. Consider enriched diet/tube feeding.	Combine surgeries and hospital admissions. Consider enriched diet/tube feeding.		Pediatrician Speech and language therapist Dietician
Orthopedic problems
Scoliosis		Physical examination of spine. Radiologic evaluation.	Physical examination of spine. Radiologic evaluation.	Physical examination of spine. Radiologic evaluation.	Orthopedic surgeon Rehabilitation specialist
Endocrinological problems
Hypogonadotropic hypogonadism	Before 6 months of age: LH and FSH testing.	Smell test, LH, FSH, estrogen/testosterone testing (from ±11 years of age).	Smell test, LH, FSH, estrogen/testosterone testing. Start hormone replacement therapy.	Continue hormone replacement therapy.	(Pediatric) endocrinologist
Hypothyroidism, hypoparathyroidism	Test when symptoms	Test when symptoms	Test when symptoms	Test when symptoms	Pediatrician/(pediatric) endocrinologist
Growth hormone deficiency		Diagnostic tests for GH deficiency. Check for scoliosis.	Diagnostic tests for GH deficiency. Check for scoliosis.

Abbreviations: CHARGE, coloboma of the eye, heart defects, atresia of the choanae, retardation of growth and/or development, genital hypoplasia, ear anomalies including hearing loss; LH, luteinizing hormone; FSH, follicle stimulating hormone; GH, growth hormone.

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