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Case Reports
. 2017 Nov 23:8:62.
doi: 10.1186/s13229-017-0178-0. eCollection 2017.

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

Anna May Kolesnik #  1 , Emily Jane Harrison Jones #  1 , Shruti Garg  2 , Jonathan Green  2 , Tony Charman  3 , Mark Henry Johnson  1 ; EDEN-BASIS Team+
Collaborators, Affiliations
Case Reports

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

Anna May Kolesnik et al. Mol Autism. .

Abstract

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.

Keywords: Adaptive functioning; Autism; Cognition; Development; Infant; NF1; Prospective longitudinal; Sensory processing; Social engagement; Translational neurodevelopment.

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Conflict of interest statement

Ethics approval and consent to participate

The study was approved by the NHS London Central and East of England Research Ethics Committees (16/EE/0167 and 06/MRE02/73); the parents of all the infant participants provided informed consent before the data collection began.

Consent for publication

Parents of infant participants consented to anonymised data being included in publications.

Competing interests

The authors declare that they have no competing interests.

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Figures

Fig. 1
Fig. 1
Average standard scores for the subscales of the Mullen Scale of Early Learning from groups of infants with LR (low familial risk of ASD), HR-no ASD (high familial risk with later typical development), HR-Atyp (high familial risk with other atypical developmental profiles), HR-ASD (high familial risk with later ASD outcome), and infants with NF1. Error bars are ± 1 SE
Fig. 2
Fig. 2
Average standard scores for the subscales of the Vineland Adaptive Behavior Scale from groups of infants with LR (low familial risk of ASD), HR-no ASD (high familial risk with later typical development), HR-Atyp (high familial risk with other atypical developmental profiles), HR-ASD (high familial risk with later ASD outcome), and infants with NF1. Error bars are ± 1 SE
Fig. 3
Fig. 3
Box-and-whisker plots showing the distribution of total scores on the Autism Observation Scale for Infants (mean, lower and upper quartile, and whiskers show full range). No statistical comparisons were carried out as the sample size for NF1 was too small. Asterisks (*) depict the individual scores from the NF1 sample. Of note, this task was added to the protocol later in the study and so was only completed by five infants
See this image and copyright information in PMC

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