Journal Article

A proof-of-concept study of growth hormone in children with Phelan–McDermid syndrome

Walker, H., Levy, T., Buxbaum, J. D., Rapaport, R., Sandin, S., Foss-Feig, J., Halpern, D., Kolevzon, A., Sethuram, S., Siper, P. M.

2022

Overview

Background Phelan–McDermid syndrome (PMS) is caused by 22q13 deletions including SHANK3 or pathogenic sequence variants in SHANK3 and is among the more common rare genetic findings in autism spectrum disorder (ASD). SHANK3 is critical for synaptic function, and preclinical and clinical studies suggest that insulin-like growth factor-1 (IGF-1) can reverse a range of deficits in PMS. IGF-1 release is stimulated by growth hormone secretion from the anterior pituitary gland, and this study sought to assess the feasibility of increasing IGF-1 levels through recombinant human growth hormone (rhGH) treatment, in addition to establishing safety and exploring efficacy of rhGH in children with PMS. Methods rhGH was administered once daily for 12 weeks to six children with PMS using an open-label design. IGF-1 levels, safety, and efficacy assessments were measured every 4 weeks throughout the study. Results rhGH administration increased levels of IGF-1 by at least 2 standard deviations and was well tolerated without serious adverse events. rhGH treatment was also associated with clinical improvement in social withdrawal, hyperactivity, and sensory symptoms. Limitations Results should be interpreted with caution given the small sample size and lack of a placebo control. Conclusions Overall, findings are promising and indicate the need for larger studies with rhGH in PMS. Trial registration NCT04003207. Registered July 1, 2019, https://clinicaltrials.gov/ct2/show/NCT04003207 .

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: ASD / Autism / Autism spectrum disorder / Autism Spectrum Disorder - genetics / Care and treatment / Caregivers / Child / Chromosome Deletion / Chromosome Disorders / Chromosomes, Human, Pair 22 / Clinical outcomes / Clinical trials / Diagnosis / Dosage and administration / Genetic variation / Growth Hormone / Growth hormones / Health aspects / Human Genetics / Human Growth Hormone - therapeutic use / Humans / Hyperactivity / Hypoglycemia / Insulin-like growth factor 1 / Insulin-Like Growth Factor I / Insulin-like growth factors / Laboratories / Letter to the Editor / Medicine / Medicine & Public Health / Neurology / Neuropsychology / Neurosciences / Pediatrics / Phelan-McDermid syndrome / PMS / Psychiatry / Shank3 / Somatotropin