Early development of infants with neurofibromatosis type 1: a case series
Authors: Anna May Kolesnik, Emily Jane Harrison Jones, Shruti Garg, Jonathan Green, Tony Charman, Mark Henry Johnson, EDEN-BASIS Team+, Simon Baron-Cohen, Jannath Begum, Patric Bolton, Celeste Cheung, Leila Dafner, Kim Davies, Mayada Elsabbagh, Janice Fernandes, Laurel Fish, Isobel Gammer, Marian Greensmith, Teea Gliga, Sarah Kalwarowsky, Michelle Liew, Greg Pasco, Andrew Pickles, Helena Ribeiro, Erica Salomone, Chloe Taylor, Leslie Tucker, Sam Wass, Emma Burkitt-Wright, D Gareth Evans, Grace Vassallo, Judith Eelloo, Siobhan West, Elizabeth Howard, Eileen Hupton, Sue Huson, Lauren Lewis, Karen Tricker, Angus Dobbie, Ruth Drimer, Saghira Malik Sharif, Diane Baralle, Carolyn Redman, Saba Sharif, Carolyn Symth, Wayne Lam, Alyson Bradbury, Neil Harrower, Oliver Quarrell, Helen Bethell, Rachel Jones, Susan Musson, Catherine Prem, Miranda Splitt, Karen Horridge, Christine Steiger, Carly Jim
Journal: Mol Autism (2017)
Keywords: adaptive functioning, autism, cognition, development, infant, nf1, prospective longitudinal, sensory processing, social engagement, translational neurodevelopment
MeSH terms: Neurofibromatosis 1 / diagnosis, Case Reports, Research Support, Non-U.S. Gov't, Activities of Daily Living, Autism Spectrum Disorder / etiology, Cognition, Communication, Female, Humans, Infant, Language Development Disorders / complications, Language Development Disorders / diagnosis, Male, Motor Activity, Neurofibromatosis 1 / complications, Prospective Studies, Risk, Temperament

Background:
Prospective studies of infants at familial risk for autism spectrum disorder (ASD) have yielded insights into the earliest signs of the disorder but represent heterogeneous samples of unclear aetiology. Complementing this approach by studying cohorts of infants with monogenic syndromes associated with high rates of ASD offers the opportunity to elucidate the factors that lead to ASD.
Methods:
We present the first report from a prospective study of ten 10-month-old infants with neurofibromatosis type 1 (NF1), a monogenic disorder with high prevalence of ASD or ASD symptomatology. We compared data from infants with NF1 to a large cohort of infants at familial risk for ASD, separated by outcome at age 3 of ASD (n = 34), atypical development (n = 44), or typical development (n = 89), and low-risk controls (n = 75). Domains assessed at 10 months by parent report and examiner observation include cognitive and adaptive function, sensory processing, social engagement, and temperament.
Results:
Infants with NF1 showed striking impairments in motor functioning relative to low-risk infants; this pattern was seen in infants with later ASD from the familial cohort (HR-ASD). Both infants with NF1 and the HR-ASD group showed communication delays relative to low-risk infants.
Conclusions:
Ten-month-old infants with NF1 show a range of developmental difficulties that were particularly striking in motor and communication domains. As with HR-ASD infants, social skills at this age were not notably impaired. This is some of the first information on early neurodevelopment in NF1. Strong inferences are limited by the sample size, but the findings suggest implications for early comparative developmental science and highlight motor functioning as an important domain to inform the development of relevant animal models. The findings have clinical implications in indicating an important focus for early surveillance and remediation in this early diagnosed genetic disorder.