Abstract
Ultrarare Marshall-Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, although questions remain. Here, development and behaviour are studied and compared in a cross-sectional study, and results are presented with genetic findings. Behavioural phenotypes are compared of eight individuals with Marshall-Smith syndrome (three male individuals) and seven with Malan syndrome (four male individuals). Long-term follow-up assessment of cognition and adaptive behaviour was possible in three individuals with Marshall-Smith syndrome. Marshall-Smith syndrome individuals have more severe ID, less adaptive behaviour, more impaired speech and less reciprocal interaction compared with individuals with Malan syndrome. Sensory processing difficulties occur in both syndromes. Follow-up measurement of cognition and adaptive behaviour in Marshall-Smith syndrome shows different individual learning curves over time. Results show significant between and within syndrome variability. Different NFIX variants underlie distinct clinical phenotypes leading to separate entities. Cognitive, adaptive and sensory impairments are common in both syndromes and increase the risk of challenging behaviour. This study highlights the value of considering behaviour within developmental and environmental context. To improve quality of life, adaptations to environment and treatment are suggested to create a better person-environment fit.
Highlights
Marshall‐Smith syndrome (MIM# 164005) and Malan syndrome (MIM# 614753) are ultrarare disorders (Prevalence < 1/1 000 000; respectively about 57 patients with Marshall–Smith syndrome and 80 patients with Malan syndrome in literature to date) caused by changes of the gene nuclear factor I X (NFIX) (Orphanet 2020a; Orphanet 2020b; Priolo et al 2018)
Marshall–Smith syndrome is characterised by abnormal bone maturation (57/57 cases), prominent forehead (55/57 cases), proptosis (55/56 cases), airway obstructions (45/55 cases), growth problems, moderate to severe intellectual disability (ID) (57/57 cases) and communication difficulties (6/6 cases) (Marshall et al 1971; Shaw et al 2010; Van Balkom et al 2011)
We aim to investigate cognition, adaptive behaviour and sensory processing by (1) describing and comparing Marshall–Smith syndrome and Malan syndrome and (2) describing long‐term follow‐up of cognition and adaptive functioning in Marshall–Smith syndrome
Summary
Marshall‐Smith syndrome (MIM# 164005) and Malan syndrome (MIM# 614753) are ultrarare disorders (Prevalence < 1/1 000 000; respectively about 57 patients with Marshall–Smith syndrome and 80 patients with Malan syndrome in literature to date) caused by changes of the gene nuclear factor I X (NFIX) (Orphanet 2020a; Orphanet 2020b; Priolo et al 2018). Intellectual disability (ID), autistic features (e.g. communication difficulties and stereotypic behaviour), sensory processing difficulties (e.g. sensitivity to noise) and sensory impairments (vision and hearing) occur in both syndromes (Van Balkom et al 2011; Priolo et al 2018) and pose major demands on families and carers. Marshall–Smith syndrome is characterised by abnormal bone maturation (57/57 cases), prominent forehead (55/57 cases), proptosis (55/56 cases), airway obstructions (45/55 cases), growth problems (height in 38/39 cases < third centile), moderate to severe ID (57/57 cases) and communication difficulties (6/6 cases) (Marshall et al 1971; Shaw et al 2010; Van Balkom et al 2011). Smith and Malan syndromes, caused by changes of the gene nuclear factor I X (NFIX), are characterised by intellectual disability (ID) and behavioural problems, questions remain. Development and behaviour are studied and compared in a cross‐sectional study, and results are presented with genetic findings
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