Hand movement in autism spectrum disorder: Answer

B. Rett syndrome The video demonstrated continuous, repetitive, clapping movements of fisted hands. This phenomenology of repetitive non-goal directed movement that was patterned, predictable, purposeless and not preceded by abnormal sensation or inner urge was suggestive of complex motor stereotypy (MS) [[1]Temudo T. Ramos E. Dias K. et al.Movement disorders in Rett syndrome: an analysis of 60 patients with detected MECP2 mutation and correlation with mutation type.Mov Disord. 2008; 23: 1384-1390Crossref PubMed Scopus (67) Google Scholar]. In view of the hallmark finding of hand MS being observed in the context of an autism spectrum disorder in a young woman, the possibility of de novo Rett syndrome (RS, OMIM 312750) was considered. The gene, methyl CpG binding protein 2 (MECP2, location: Xq28) [[1]Temudo T. Ramos E. Dias K. et al.Movement disorders in Rett syndrome: an analysis of 60 patients with detected MECP2 mutation and correlation with mutation type.Mov Disord. 2008; 23: 1384-1390Crossref PubMed Scopus (67) Google Scholar], was analyzed by polymerase chain reaction and bidirectional sequencing of the coding region and exon-intron splice junctions. A multiplex ligation-dependent probe amplification assay (MLPA kit no. P015-F1, MRC Holland) was performed to test for the deletion or duplication of one or more entire exon(s) in the gene. A heterozygous nonsense mutation in exon 4 of the MECP2 gene (c.796A>T, p.Lys266∗) was identified (Answer supplementary Fig. 1), thereby confirming the diagnosis of RS. The repertoire of hand MS in RS includes clapping, tapping, flapping, waving, wringing, squeezing, clenching, patting, picking, washing, rubbing or mouthing movements. Other MS in RS involve the body (e.g., rocking movements) or legs (e.g., shifting weight from one leg to the other). MS is differentiated from other phenomenologies such as tics, mannerism, habits, compulsion, automatism, akathisia, substance-use-related punding and paroxysmal dyskinesias by the clinical features such as the age at symptom onset, body distribution, duration, rhythmicity, absence of premonitory sensation, intrusion/obsession, suppressibility, inner urge and waxing/waning course [[2]Prioni S. Fetoni V. Barocco F. et al.Stereotypic behaviors in degenerative dementias.J Neurol. 2012; 259: 2452-2459Crossref PubMed Scopus (22) Google Scholar]. Apart from RS, MS can also be observed in other autism spectrum disorders, Angelman syndrome, Tourette syndrome, tardive dyskinesia, levodopa-induced dyskinesia in Parkinson disease, frontotemporal dementia, restless leg syndrome, neuroacanthocytosis, neuroferritinopathy and Lesch-Nyhan syndrome [[2]Prioni S. Fetoni V. Barocco F. et al.Stereotypic behaviors in degenerative dementias.J Neurol. 2012; 259: 2452-2459Crossref PubMed Scopus (22) Google Scholar]. In some of these conditions, phonic stereotypies, self-mutilating behavior and other movement disorders accompany the stereotyped movements. Our patient did not have the clinical or imaging features of tuberous sclerosis complex, eponymously known as Bourneville syndrome. She was managed in a multi-disciplinary rehabilitation team and received risperidone for intermittent agitation and carbamazepine for seizure disorder. Of note, her motor stereotypy preceded the introduction of these medications. Dr. Ramachandiran Nandhagopal contributed to the conceptualization, organization, provision of intellectual input and presentation of the manuscript. He evaluated and treated the patient, provided the video recording of the motor stereotypy, drafted the first version of the manuscript and provided intellectual inputs. Mr. Douglas Friday and Dr. Stefan Weiss performed the molecular genetic testing and provided the image of DNA sequence chromatogram. eyJraWQiOiI4ZjUxYWNhY2IzYjhiNjNlNzFlYmIzYWFmYTU5NmZmYyIsImFsZyI6IlJTMjU2In0.eyJzdWIiOiIxMWEwNmNiYmRjNTlkYWEyN2YzYTA1MTE1ZTZlMzVmMyIsImtpZCI6IjhmNTFhY2FjYjNiOGI2M2U3MWViYjNhYWZhNTk2ZmZjIiwiZXhwIjoxNjc4MjQ5OTc1fQ.goEgy5kYE9SlA2CngOIxTrPvOH1MUMZwGGfIWfWOeoVKNdKaFT_-CM4PwvISm0HmlsuAl3c_QcMBwj8-my0tQI4e3JYCFMTGnmkL1wOz0bWzsM6DoBH9anzOnUlc7f4qH1E0ALJRn_cx2CHzS4vd3gSsZbgZ9P9-zoM13KY6EeZLM8KPqL0yKfAtVaidCiPrP2Jw3ueRfaojdjeknQAllV6xq2jSnMV6kv8N-pKm6bW5zCKk8b9EVmWsqxgw67lYat9ywZFiOBxbBoKruTnoFOGS71zchmxtht7P0IRXwg8R0_6RHDllm5penZvRRCAwc6lNBQx5X4A4y4_fLkMuXQ Download .mp4 (2.95 MB) Help with .mp4 files Supplementary video 1 Hand movement in autism spectrum disorder: QuestionJournal of Clinical NeuroscienceVol. 41PreviewA 16-year-old woman presented with psychomotor regression, autistic features and abnormal hand movements from age 2 and generalized seizures from age 10. She was born of consanguineous parentage and had normal birth and neonatal development. There was no family history of autism. On examination, she made no eye contact and had microcephaly, profound intellectual disability and was mute. She had lost the purposeful use of her hands and feet and demonstrated frequent hand movement (see Video 1). The rest of her neurological examination and MRI brain were unremarkable. Full-Text PDF