Hirofumi Kurata1, Kentaro Shirai2, Yoshiaki Saito3, Tetsuya Okazaki4, Koyo Ohno3, Masayoshi Oguri5, Kaori Adachi6, Eiji Nanba6, Yoshihiro Maegaki3. 1. Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan. Electronic address: kurata0708@med.tottori-u.ac.jp. 2. Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan; Department of Pediatrics, Tsuchiura Kyodo General Hospital, Tsuchiura, Japan. 3. Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan. 4. Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan; Division of Clinical Genetics, Tottori University Hospital, Yonago, Japan. 5. Division of Child Neurology, Department of Brain and Neurosciences, Faculty of Medicine, Tottori University, Yonago, Japan; Department of Pathobiological Science and Technology, Faculty of Medicine, Tottori University, Yonago, Japan. 6. Division of Clinical Genetics, Tottori University Hospital, Yonago, Japan.
Abstract
PURPOSE: To clarify the relationship between macrocephaly and neurodevelopmental disorders, as well as identify the prevalence of PTEN mutations in autism spectrum disorders with macrocephaly in Japan. SUBJECTS AND METHODS: Diagnostic and other medical information of children with macrocephaly younger than 4years (n=93) were collected for analysis. PTEN gene mutation analysis was conducted in another set of 16 macrocephalic individuals aged 3-22years. RESULTS: Sixteen macrocephalic children were associated with neurodevelopmental disorders, including autism spectrum disorders (ASDs) (n=6), autistic traits (n=5), intellectual disability (n=5), attention deficit hyperactivity disorder (n=1), developmental coordination disorders (n=1), and language disorder (n=1). Male gender was significantly linked to these disorders, whereas a family history and degree of macrocephaly were not significantly linked to the diagnosis. A novel mutation in the PTEN gene was identified in a 16-year-old girl with autism, mental retardation, language delay, extreme macrocephaly (+4.7SD) with a prominent forehead, and digital minor anomalies. CONCLUSION: Children with macrocephaly, particularly males, are at a higher risk of neurodevelopmental disorders, rather than progressive etiologies, such as hydrocephalus and neurodegenerative disorders. The data provide a basis for routine health checks for young children in Japan, including the follow-up management and possible screening of PTEN mutations in children with ASDs and macrocephaly.
PURPOSE: To clarify the relationship between macrocephaly and neurodevelopmental disorders, as well as identify the prevalence of PTEN mutations in autism spectrum disorders with macrocephaly in Japan. SUBJECTS AND METHODS: Diagnostic and other medical information of children with macrocephaly younger than 4years (n=93) were collected for analysis. PTEN gene mutation analysis was conducted in another set of 16 macrocephalic individuals aged 3-22years. RESULTS: Sixteen macrocephalic children were associated with neurodevelopmental disorders, including autism spectrum disorders (ASDs) (n=6), autistic traits (n=5), intellectual disability (n=5), attention deficit hyperactivity disorder (n=1), developmental coordination disorders (n=1), and language disorder (n=1). Male gender was significantly linked to these disorders, whereas a family history and degree of macrocephaly were not significantly linked to the diagnosis. A novel mutation in the PTEN gene was identified in a 16-year-old girl with autism, mental retardation, language delay, extreme macrocephaly (+4.7SD) with a prominent forehead, and digital minor anomalies. CONCLUSION:Children with macrocephaly, particularly males, are at a higher risk of neurodevelopmental disorders, rather than progressive etiologies, such as hydrocephalus and neurodegenerative disorders. The data provide a basis for routine health checks for young children in Japan, including the follow-up management and possible screening of PTEN mutations in children with ASDs and macrocephaly.
Authors: Sheng Chih Jin; Weilai Dong; Adam J Kundishora; Shreyas Panchagnula; Andres Moreno-De-Luca; Charuta G Furey; August A Allocco; Rebecca L Walker; Carol Nelson-Williams; Hannah Smith; Ashley Dunbar; Sierra Conine; Qiongshi Lu; Xue Zeng; Michael C Sierant; James R Knight; William Sullivan; Phan Q Duy; Tyrone DeSpenza; Benjamin C Reeves; Jason K Karimy; Arnaud Marlier; Christopher Castaldi; Irina R Tikhonova; Boyang Li; Helena Perez Peña; James R Broach; Edith M Kabachelor; Peter Ssenyonga; Christine Hehnly; Li Ge; Boris Keren; Andrew T Timberlake; June Goto; Francesco T Mangano; James M Johnston; William E Butler; Benjamin C Warf; Edward R Smith; Steven J Schiff; David D Limbrick; Gregory Heuer; Eric M Jackson; Bermans J Iskandar; Shrikant Mane; Shozeb Haider; Bulent Guclu; Yasar Bayri; Yener Sahin; Charles C Duncan; Michael L J Apuzzo; Michael L DiLuna; Ellen J Hoffman; Nenad Sestan; Laura R Ment; Seth L Alper; Kaya Bilguvar; Daniel H Geschwind; Murat Günel; Richard P Lifton; Kristopher T Kahle Journal: Nat Med Date: 2020-10-19 Impact factor: 53.440
Authors: Susan M Hiatt; Michelle L Thompson; Jeremy W Prokop; James M J Lawlor; David E Gray; E Martina Bebin; Tuula Rinne; Marlies Kempers; Rolph Pfundt; Bregje W van Bon; Cyril Mignot; Caroline Nava; Christel Depienne; Louisa Kalsner; Anita Rauch; Pascal Joset; Ruxandra Bachmann-Gagescu; Ingrid M Wentzensen; Kirsty McWalter; Gregory M Cooper Journal: Am J Hum Genet Date: 2019-03-14 Impact factor: 11.025