Myotonic dystrophy type 1 (DM1) belongs to the broad spectrum of genetic disorders associated with autism spectrum disorders (ASD). ASD were reported predominantly in congenital and early childhood forms of DM1. We describe dizygotic twin boys with ASD who were referred for routine laboratory genetic testing and in whom karyotyping, FMR1 gene testing, and single nucleotide polymorphism array analysis yielded negative results. The father of the boys was later diagnosed with suspected DM1, and testing revealed characteristic DMPK gene expansions in his genome as well as in the genomes of both twins and their elder brother, who also suffered from ASD. In accord with previous reports on childhood forms of DM1, our patients showed prominent neuropsychiatric phenotypes characterized especially by hypotonia, developmental and language delay, emotional and affective lability, lowered adaptability, and social withdrawal. The experience with this family and multiple literature reports of ASD in DM1 on the one side but the lack of literature data on the frequency of DMPK gene expansions in ASD patients on the other side prompted us to screen the DMPK gene in a sample of 330 patients with ASD who were first seen by a geneticist before they were 10 years of age, before the muscular weakness, which may signal DM1, usually becomes obvious. The absence of any DMPK gene expansions in this cohort indicates that targeted DMPK gene testing can be recommended only in ASD patients with specific symptoms or family history suggestive of DM1.

Department of Biology and Medical Genetics

Department of Child Neurology Charles University 2nd Faculty of Medicine and University Hospital Motol

Department of Child Psychiatry

Gennet Centre for Fetal Medicine Prague Czech Republic

Zobrazit více v PubMed

De Rubeis S, Buxbaum JD. Genetics and genomics of autism spectrum disorder: embracing complexity. Hum Mol Genet. 2015;24(R1):R24–R31. PubMed PMC

Zafeiriou DI, Ververi A, Dafoulis V, Kalyva E, Vargiami E. Autism spectrum disorders: the quest for genetic syndromes. Am J Med Genet B Neuropsychiatr Genet. 2013;162B(4):327–366. PubMed

Toriello HV. Approach to the genetic evaluation of the child with autism. Pediatr Clin North Am. 2012;59(1):113–128. PubMed

Harley HG, Rundle SA, MacMillan JC, et al. Size of the unstable CTG repeat sequence in relation to phenotype and parental transmission in myotonic dystrophy. Am J Hum Genet. 1993;52(6):1164–1174. PubMed PMC

Echenne B, Bassez G. Congenital and infantile myotonic dystrophy. Handb Clin Neurol. 2013;113:1387–1393. PubMed

Ho G, Cardamone M, Farrar M. Congenital and childhood myotonic dystrophy: current aspects of disease and future directions. World J Clin Pediatr. 2015;4(4):66–80. PubMed PMC

Yoshimura I, Sasaki A, Akimoto H, Yoshimura N. A case of congenital myotonic dystrophy with infantile autism. No To Hattatsu. 1989;21(4):379–384. PubMed

Blondis TA, Cook E, Jr, Koza-Taylor P, Finn T. Asperger syndrome associated with Steinert’s myotonic dystrophy. Dev Med Child Neurol. 1996;38(9):840–847. PubMed

Paul M, Allington-Smith P. Asperger syndrome associated with Steinert’s myotonic dystrophy. Dev Med Child Neurol. 1997;39(4):280–281. PubMed

Steyaert J, Umans S, Willekens D, et al. A study of the cognitive and psychological profile in 16 children with congenital or juvenile myotonic dystrophy. Clin Genet. 1997;52(3):135–141. PubMed

Ekström AB, Hakenäs-Plate L, Samuelsson L, Tulinius M, Wentz E. Autism spectrum conditions in myotonic dystrophy type 1: a study on 57 individuals with congenital and childhood forms. Am J Med Genet B Neuropsychiatr Genet. 2008;147B(6):918–926. PubMed

Warner JP, Barron LH, Goudie D, et al. A general method for the detection of large CAG repeat expansions by fluorescent PCR. J Med Genet. 1996;33(12):1022–1026. PubMed PMC

Musova Z, Mazanec R, Krepelova A, et al. Highly unstable sequence interruptions of the CTG repeat in the myotonic dystrophy gene. Am J Med Genet A. 2009;149A(7):1365–1374. PubMed

Saluto A, Brussino A, Tassone F, et al. An enhanced polymerase chain reaction assay to detect pre- and full mutation alleles of the fragile X mental retardation 1 gene. J Mol Diagn. 2005;7(5):605–612. PubMed PMC

Kamsteeg EJ, Kress W, Catalli C, et al. Best practice guidelines and recommendations on the molecular diagnosis of myotonic dystrophy types 1 and 2. Eur J Hum Genet. 2012;20(12):1203–1208. PubMed PMC

Echenne B, Rideau A, Roubertie A, Sébire G, Rivier F, Lemieux B. Myotonic dystrophy type I in childhood long-term evolution in patients surviving the neonatal period. Eur J Paediatr Neurol. 2008;12(3):210–223. PubMed

Steyaert J, de Die-Smulders C, Fryns JP, Goossens E, Willekens D. Behavioral phenotype in childhood type of dystrophia myotonica. Am J Med Genet. 2000;96(6):888–889. PubMed

Kalkman JS, Schillings ML, Zwarts MJ, van Engelen BG, Bleijenberg G. Psychiatric disorders appear equally in patients with myotonic dystrophy, facioscapulohumeral dystrophy, and hereditary motor and sensory neuropathy type I. Acta Neurol Scand. 2007;115(4):265–270. PubMed

Douniol M, Jacquette A, Cohen D, et al. Psychiatric and cognitive phenotype of childhood myotonic dystrophy type 1. Dev Med Child Neurol. 2012;54(10):905–911. PubMed

Suliman R, Ben-David E, Shifman S. Chromatin regulators, phenotypic robustness, and autism risk. Front Genet. 2014;5:81. PubMed PMC

Gladman JT, Mandal M, Srinivasan V, Mahadevan MS. Age of onset of RNA toxicity influences phenotypic severity: evidence from an inducible mouse model of myotonic dystrophy (DM1) PLoS One. 2013;8(9):e72907. PubMed PMC