Development, behaviour and sensory processing in Marshall–Smith syndrome and Malan syndrome: phenotype comparison in two related syndromes

• Published in: Journal of intellectual disability research Vol. 64; no. 12; pp. 956 - 969
• Main Authors: Mulder, P. A., Balkom, I. D. C., Landlust, A. M., Priolo, M., Menke, L. A., Acero, I. H., Alkuraya, F. S., Arias, P., Bernardini, L., Bijlsma, E. K., Cole, T., Coubes, C., Dapia, I., Davies, S., Di Donato, N., Elcioglu, N. H., Fahrner, J. A., Foster, A., González, N. G., Huber, I., Iascone, M., Kaiser, A.‐S., Kamath, A., Kooblall, K., Lapunzina, P., Liebelt, J., Lynch, S. A., Maas, S. M., Mammì, C., Mathijssen, I. B., McKee, S., Mirzaa, G. M., Montgomery, T., Neubauer, D., Neumann, T. E., Pintomalli, L., Pisanti, M. A., Plomp, A. S., Price, S., Salter, C., Santos‐Simarro, F., Sarda, P., Schanze, D., Segovia, M., Shaw‐Smith, C., Smithson, S., Suri, M., Tatton‐Brown, K., Tenorio, J., Thakker, R. V., Valdez, R. M., Van Haeringen, A., Van Hagen, J. M., Zenker, M., Zollino, M., Dunn, W. W., Piening, S., Hennekam, R. C.
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01-12-2020
• Subjects: Abnormalities, Multiple - epidemiology; Abnormalities, Multiple - physiopathology; Adaptation, Psychological; Adaptive behavior; adaptive behaviour; Adolescent; Adult; Behavior; Behavior problems; Bone Diseases, Developmental - epidemiology; Bone Diseases, Developmental - physiopathology; Child; Child, Preschool; Cognition; Cognitive aspects; Comorbidity; Craniofacial Abnormalities - epidemiology; Craniofacial Abnormalities - physiopathology; Cross-Sectional Studies; Evaluation; Female; Follow-Up Studies; Humans; Intellectual disabilities; Intellectual Disability - epidemiology; Intellectual Disability - physiopathology; Malan syndrome; Male; Marshall–Smith syndrome; Measurement; Mental Disorders - epidemiology; Mental Disorders - physiopathology; Netherlands - epidemiology; NFIX variants; Phenotype; Phenotypes; Quality of life; Risk behavior; Sensory perception; Sensory processes; sensory processing; Septo-Optic Dysplasia - epidemiology; Septo-Optic Dysplasia - physiopathology; Social development; Speech; Speech Disorders - epidemiology; Speech Disorders - physiopathology; Syndrome; Variants; Young Adult; Netherlands; NFIX variants; sensory processing; Malan syndrome; cognition; Marshall-Smith syndrome; adaptive behaviour
• ISSN: 0964-2633; 1365-2788
• DOI: 10.1111/jir.12787

Background
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.
Methods
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.
Results
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.
Conclusions
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.