De novo translocation t(5;18)(q33.1;q12.1) associated with autistic disorder

Autism is a relatively common and heterogenous neuropsychiatric disorder characterized by reduced social and interindividual contacts and interactions. Autism usually starts in early childhood. Complete absence of eye contact and speech can be observed in severe forms of autism. Due to problems of defining the wide spectrum of children with the triad of impairments of social interaction, communication, and imagination, the prevalence of autismhas been reported to vary from 2 to 64 per 10,000 [Smalley et al., 1988; Chakrabarti and Fombonne, 2001]. It cannot be ruled out that prevalence rates have increased overtime. Studies of familial cases have demonstrated that genetic factors are involved in the etiology of autism. A number of balanced and unbalanced chromosomal aberrations have been found to be associated with autism [Gillberg, 1998; Wassink et al., 2001; Shao et al., 2003]. In several monogenic disorders, like fragile X syndrome [MIM 309550] and Rett syndrome [MIM no. 312750], it has been possible to identify a single gene that can lead to autistic-like behavior in some affected individuals. However, nomajor gene for autism has yet been identified. In this study we describe a reciprocal translocation t(5;18)(q33.1;q12.1) that occurred de novo in a 13-year-old boy with autism and psychomotor retardation and only minor additional anomalies or dysmorphic features. Neither chromosomal breakpoint has beenmentioned in previous reports of cytogenetic aberrations seen inpatientswith autistic behavior. Our patient (Fig. 1) was born as the son of unrelated parents after an uncomplicated pregnancy and delivery in the 40th week of gestation. Birth weight was 4,130 g (>90th centile), length 54 cm (>90th centile), and head circumference (OFD) 37 cm (>90th centile). Apgar score was 9/10/10. Maternal and paternal ages were 21 and 22 years, respectively. Three days after birth the patient was hospitalised for 12 days to treat an otherwise uncomplicated bronchopneumonia. The following neonatal period was normal and routinely performed pediatric examinations did not show obvious anomalies up to the age of 10 months. At this age he started to walk. However, right from the very beginning, only toe walking was observed, and at 18 months stereotypic hand movements were noticed more frequently. There was no development of speech and language. In the following months he became more difficult to handle, was very shy, and started crying frequently for no apparent reason. Missing or grossly reduced eye contact and presence of stereotypical hand movements became evident. It took until theage of 26months for psychomotor symptoms, and especially mental retardation to be diagnosed. Subsequently he received intensive special intervention and regular training at the kindergarten. Finally, at 31⁄2 years of age, the diagnosis of autism was made, because of the typical autistic features (described below). To improve his cognitive andmotor skills, he was integrated into an intensive special training program.His initial response was very aggressive. However with consequent and repeated positive and negative feedback, he slowly began to achieve simple tasks. At re-evaluation at 12/12, in addition to the clinical examination, the questionnaire Autism Diagnostic InterviewRevised Schedule [ADI-R; Lord et al., 1994] and a systematic observation using the Autism Diagnostic Observation Schedule [ADOS; Lord et al., 1989] were applied. We have no IQscore because the boy is not cooperative. The results from the ADI-R, which was performed with the mother, show qualitative deficits in all fields: interactive reciprocal social interaction, communication and language, repetitive, restrictive, and stereotyped behavior as well as abnormal development before the age of 36 months. In all functions the score was higher than the ‘‘Cut-Off,’’ thus a postive diagnosis of ‘‘autism’’ was made. The ADOS-Module 2 was performed in the patient’s home environment with the assistance of a nurse. The test could not be applied rigorously, because the child showed extreme restlessness, and only short episodes of interactive behavior could be observed. The child did not show any creative game and no reciprocity. He consistently responded when the examiner called his name. His conversation was limited to 2-item phrases such as ‘‘please chocolate, please juice, Margit come! ’’ The child understands short precise sentences and most often expresses needs by one-word-items. He accepts children trying to get in contact with him, but prefers contact with adults (parents, nurse, and other well-known persons). Usually he does not establish contactwith other children.He does not play with other children who contact him. He shows stereotyped behavior, knocking with one object or clapping one hand against the other, or turning a straw or pencil. Aggression towards others is seen rarely, sometimes the child shows autoaggression. His passions are movie pictures. Uponphysical examinationat 13yearshisheightwas171cm (>90th centile), weight was 51 kg (75–90th centile), and head circumference was 57 cm (>97th centile). Head circumference of the parents was normal (father: 56 cm; mother 54 cm). Based on our clinical evaluation and on pediatric records he shows normal morphology with very minor dysmorphic signs like slight downslanting palpebral fissures, deep set eyes, and protruding teeth. Mainly on his left upper back he showed several large hyper pigmented cutaneous spots with irregular margins not following the lines of Blaschko. Wood lamp examination did not show any additional anomaly of pigmentation. Gynecomastia was noticed but his pubertal development, currently Tanner P3-4, G 3 is only slightly delayed. He attends a school for the mentally disabled. No anomalies of inner organs, as determined by ultrasound and X-rays, nor of brain, Grant sponsor: Oesterreichische Nationalbank (to E.P.); Grant number: 9522.