Potocki-Lupski syndrome (PTLS) and Smith-Magenis syndrome (SMS) are related genomic disorders, as duplication 17p11.2 (associated with PTLS) is the reciprocal recombination product of the SMS microdeletion. While SMS has a relatively well-delineated behavioural phenotype, the behavioural profile in PTLS is less well defined, despite purported associations with autism spectrum disorder (ASD) and the suggestion that some behaviours may be diametric to those seen in SMS.
Caregivers of individuals with PTLS (N = 34; M age = 12.43, SD = 6.78) completed online behavioural questionnaires, including the Challenging Behaviour Questionnaire (CBQ), the Activity Questionnaire (TAQ), the Repetitive Behaviour Questionnaire (RBQ), the Mood, Interest and Pleasure Questionnaire-Short Form (MIPQ-S) and the Social Communication Questionnaire (SCQ), which assesses behaviours associated with ASD. Individuals with PTLS were matched on age and adaptive functioning to individuals with SMS (N = 31; M age = 13.61, SD = 6.85) and individuals with idiopathic ASD (N = 33; M age = 12.04, SD = 5.85) from an existing dataset.
Individuals with PTLS and SMS were less impaired than those with idiopathic ASD on the communication and reciprocal social interaction subscales of the SCQ, but neither syndrome group differed from idiopathic ASD on the restricted, repetitive and stereotyped behaviours subscale. On the repetitive behaviour measure, individuals with PTLS and idiopathic ASD scored higher than individuals with SMS on the compulsive behaviour subscale. Rates of self-injury and property destruction were significantly lower in PTLS and idiopathic ASD than in SMS. No between-syndrome differences were found in relation to overactivity or mood; however, impulsivity was greater in SMS than in PTLS.
Findings suggest some overlap in the behavioural phenotype of PTLS and features of ASD symptomatology; however, the overall profile of behaviours in PTLS appears to be divergent from both idiopathic ASD and SMS. Relative to idiopathic ASD, PTLS is not characterised by communication or social interaction deficits. However, restricted and repetitive behaviours were evident in PTLS, and these may be characterised specifically by compulsive behaviours. While several behavioural differences were identified between PTLS and SMS, there was little evidence of diametric behavioural phenotypes, particularly in relation to social behaviour.
Potocki L, Bi W, Treadwell-Deering D, Carvalho CM, Eifert A, Friedman EM, et al. Characterization of Potocki-Lupski syndrome (dup (17)(p11. 2p11. 2)) and delineation of a dosage-sensitive critical interval that can convey an autism phenotype. Am J Hum Genet. 2007;80(4):633–49. CrossRefPubMedPubMedCentral
Dykens EM. Measuring behavioral phenotypes: provocations from the “new genetics”. Am J Ment Retard. 1995;99(5):522–32. PubMed
Slager RE, Newton TL, Vlangos CN, Finucane B, Elsea SH. Mutations in rai1 associated with Smith–Magenis syndrome. Nat Genet. 2003;33(4):466–8.
Bouras N, Dykens EM, Smith AC. Distinctiveness and correlates of maladaptive behaviour in children and adolescents with Smith-Magenis syndrome. J Intellect Disabil Res. 1998;42(6):481–9. CrossRef
Neira-Fresneda J, Potocki L. Neurodevelopmental disorders associated with abnormal gene dosage: Smith-Magenis and Potocki-Lupski syndromes. J Pediatr Gen. 2015;4(03):159–67. CrossRef
Bi W, Yan J, Shi X, Yuva-Paylor LA, Antalffy BA, Goldman A, et al. Rai1 deficiency in mice causes learning impairment and motor dysfunction, whereas rai1 heterozygous mice display minimal behavioral phenotypes. Hum Mol Genet. 2007;16(15):1802–13.
Thompson T, Butler MG, MacLean WE Jr, Joseph B, Delaney D. Cognition, behavior, neurochemistry, and genetics in Prader-Willi syndrome. In: Tager-Flusburg H, editor. Neurodevelopmental Disorders. Cambridge: MIT Press; 1999. p. 155–78.
Dykens EM, Cassidy SB, DeVries ML. Prader-Willi syndrome. In: Goldstein S, Reynolds CR, editors. Handbook of neurodevelopmental and genetic disorders in children. New York: Guildford Press; 2011. p. 484–511.
Nakamine A, Ouchanov L, Jiménez P, Manghi ER, Esquivel M, Monge S, et al. Duplication of 17 (p11. 2p11. 2) in a male child with autism and severe language delay. Am J Med Genet A. 2008;146(5):636–43. CrossRef
Kushlick A, Blunden R, Cox G. A method of rating behaviour characteristics for use in large scale surveys of mental handicap. Psychol Med. 1973;3(4):466-78.
Frick RW. Accepting the null hypothesis. Mem Cognit. 1995;23(1):132-8.
Witwer AN, Lecavalier L. Autism screening tools: an evaluation of the social communication questionnaire and the developmental behaviour checklist-autism screening algorithm. J Intellect Develop Disabil. 2007;32(3):179–87. CrossRef
Moss J, Oliver C. Repetitive Behaviour Questionnaire: manual for administration and scorer interpretation. Birmingham: University of Birmingham; 2008.
McHugh ML. Interrater reliability: the kappa statistic. Biochem Med. 2012;22(3):276–82. CrossRef
Ross E, Arron K, Oliver C. The mood interest and pleasure questionnaire: manual for administration and scoring. Birmingham: University of Birmingham; 2008.
Burbidge C, Oliver C. Activity questionnaire: manual for administration and scorer interpretation. Birmingham: University of Birmingham; 2008.
Moog U, Engelen JJ, Weber BW, Van Gelderen M, Steyaert J, Baas F, et al. Hereditary motor and sensory neuropathy (HMSN) IA, developmental delay and autism related disorder in a boy with duplication (17)(p11. 2p12). Genet Couns. 2004;15(1):73–80. PubMed
Udwin O. Williams and Smith-Magenis syndromes. In: Howlin P, Udwin O, editors. Outcomes in neurodevelopmental and genetic disorders. Cambridge: Cambridge University Press; 2002.
Finucane B, Simon E. Genetics and dual diagnosis: Smith-Magenis syndrome. NADD Bulletin. 1999;2(1):8–10.
Lord C, Rutter M, DiLavore P, Risi S, Gotham K, Bishop SL. Autism diagnostic observation schedule (ADOS) manual. Western Psychological Services: Los Angeles; 1999.
Schaer M, Kochalka J, Padmanabhan A, Supekar K, Menon V. Sex differences in cortical volume and gyrification in autism. Mol Autism. 2015;4(6):42. CrossRef
- The behavioural phenotype of Potocki-Lupski syndrome: a cross-syndrome comparison
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