Early development of infants with neurofibromatosis type 1: a case series

Abstract

BackgroundProspective 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.MethodsWe 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.ResultsInfants 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.ConclusionsTen-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.Electronic supplementary materialThe online version of this article (10.1186/s13229-017-0178-0) contains supplementary material, which is available to authorized users.

Prediction of Autism at 3 Years from Behavioural and Developmental Measures in High-Risk Infants: A Longitudinal Cross-Domain Classifier Analysis

“…In particular, delays in high-risk infants who later developed ASD tended to start in the motor domain at 8 months and extend to the social domain by 14 months. This confirms and extends previous findings to high-risk siblings who received a clinical outcome evaluation at 36 months (Estes et al 2015 ; Kolesnik et al 2017 ). However, we found differences between HR-ASD and HR-Typical on Mullen receptive but not expressive language scores, and between LR and HR-ASD or HR-Atypical on Mullen language scores and Vineland communication scores already at 8 months.…”

“…VABS + AOSI vs. VABS alone) suggested that data integration improved predictive performance, though this was only marginally significant after correcting for multiple comparisons. While delays in motor skills have been previously documented in the first year of life (Leonard et al 2014 ; Libertus et al 2014 ), the improved predictive accuracy of integrated communication and motor scores is in contrast with previous findings supporting the emergence of ASD in the sensorimotor domain before 12 months, and moving only later to the social-communication domain (Estes et al 2015 ; Kolesnik et al 2017 ). However, this might be explained by the inclusion of siblings with early emerging language delays, but not ASD, when classification of ASD is extended to classification of broader atypicality.…”

Social skills in children with RASopathies: a comparison of Noonan syndrome and neurofibromatosis type 1

“…Given some research suggesting that social impairment may be less apparent in younger children with RASopathies, or that individuals may show declining performance relative to peers as they grow older [ 35 , 36 ], we examined the correlation between age and social skills in each of the groups. No association between age and SSIS Social Skills scores was found in the NS group, r = − 0.04, p = 0.787 or the sibling comparison group, r = 0.14, p = 0.452.…”

Cognitive Issues Experienced by Individuals Living with Neurofibromatosis

“…Weaknesses with aspects of language have been found in populations with NF1. Delays in early language development have been noted children as young as 10 months, which appear to persist [20,35,36]. NF1 has been associated with weaknesses with nearly all aspects of language; however, studies have not been consistent [37,38].…”