Anne C Wheeler1, Angela Gwaltney2, Melissa Raspa2, Katherine C Okoniewski2, Elizabeth Berry-Kravis3, Kelly N Botteron4, Dejan Budimirovic5, Heather Cody Hazlett6, David Hessl7, Molly Losh8, Gary E Martin9, Susan M Rivera7,10, Jane E Roberts11, Donald B Bailey2. 1. Research Triangle Institute International, Research Triangle Park, North Carolina; acwheeler@rti.org. 2. Research Triangle Institute International, Research Triangle Park, North Carolina. 3. Department of Pediatrics, Rush Medical College, Chicago, Illinois. 4. Departments of Psychiatry and Radiology, School of Medicine, Washington University, St Louis, Missouri. 5. Kennedy Krieger Institute, Baltimore, Maryland. 6. Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina. 7. Department of Psychiatry and Behavioral Sciences, MIND Institute, Sacramento, California. 8. School of Communication, Northwestern University, Evanston, Illinois. 9. Department of Communication Sciences and Disorders, St. John's University, Staten Island, New York. 10. Department of Psychology, College of Letters and Science, University of California, Davis, Davis, California; and. 11. Department of Psychology, University of South Carolina, Columbia, South Carolina.
Abstract
BACKGROUND: Children with FMR1 gene expansions are known to experience a range of developmental challenges, including fragile X syndrome. However, little is known about early development and symptom onset, information that is critical to guide earlier identification, more accurate prognoses, and improved treatment options. METHODS: Data from 8 unique studies that used the Mullen Scales of Early Learning to assess children with an FMR1 gene expansion were combined to create a data set of 1178 observations of >500 young children. Linear mixed modeling was used to explore developmental trajectories, symptom onset, and unique developmental profiles of children <5 years of age. RESULTS: Boys with an FMR1 gene full mutation showed delays in early learning, motor skills, and language development as young as 6 months of age, and both sexes with a full mutation were delayed on all developmental domains by their second birthday. Boys with a full mutation continued to gain skills over early childhood at around half the rate of their typically developing peers; girls with a full mutation showed growth at around three-quarters of the rate of their typically developing peers. Although children with a premutation were mostly typical in their developmental profiles and trajectories, mild but significant delays in fine motor skills by 18 months were detected. CONCLUSIONS: Children with the FMR1 gene full mutation demonstrate significant developmental challenges within the first 2 years of life, suggesting that earlier identification is needed to facilitate earlier implementation of interventions and therapeutics to maximize effectiveness.
BACKGROUND: Children with FMR1 gene expansions are known to experience a range of developmental challenges, including fragile X syndrome. However, little is known about early development and symptom onset, information that is critical to guide earlier identification, more accurate prognoses, and improved treatment options. METHODS: Data from 8 unique studies that used the Mullen Scales of Early Learning to assess children with an FMR1 gene expansion were combined to create a data set of 1178 observations of >500 young children. Linear mixed modeling was used to explore developmental trajectories, symptom onset, and unique developmental profiles of children <5 years of age. RESULTS: Boys with an FMR1 gene full mutation showed delays in early learning, motor skills, and language development as young as 6 months of age, and both sexes with a full mutation were delayed on all developmental domains by their second birthday. Boys with a full mutation continued to gain skills over early childhood at around half the rate of their typically developing peers; girls with a full mutation showed growth at around three-quarters of the rate of their typically developing peers. Although children with a premutation were mostly typical in their developmental profiles and trajectories, mild but significant delays in fine motor skills by 18 months were detected. CONCLUSIONS: Children with the FMR1 gene full mutation demonstrate significant developmental challenges within the first 2 years of life, suggesting that earlier identification is needed to facilitate earlier implementation of interventions and therapeutics to maximize effectiveness.
Authors: Donald B Bailey; Elizabeth Berry-Kravis; Louise W Gane; Sonia Guarda; Randi Hagerman; Cynthia M Powell; Flora Tassone; Anne Wheeler Journal: Pediatrics Date: 2017-06 Impact factor: 7.124
Authors: H E Malter; J C Iber; R Willemsen; E de Graaff; J C Tarleton; J Leisti; S T Warren; B A Oostra Journal: Nat Genet Date: 1997-02 Impact factor: 38.330
Authors: Anne C Wheeler; Donald B Bailey; Elizabeth Berry-Kravis; Jan Greenberg; Molly Losh; Marsha Mailick; Montserrat Milà; John M Olichney; Laia Rodriguez-Revenga; Stephanie Sherman; Leann Smith; Scott Summers; Jin-Chen Yang; Randi Hagerman Journal: J Neurodev Disord Date: 2014-07-30 Impact factor: 4.025
Authors: Anne C Wheeler; John Sideris; Randi Hagerman; Elizabeth Berry-Kravis; Flora Tassone; Donald B Bailey Journal: J Neurodev Disord Date: 2016-11-03 Impact factor: 4.025
Authors: Katherine C Okoniewski; Anne C Wheeler; Stacey Lee; Beth Boyea; Melissa Raspa; Jennifer L Taylor; Donald B Bailey Journal: Brain Sci Date: 2019-01-03
Authors: Laura Katus; Bosiljka Milosavljevic; Maria Rozhko; Samantha McCann; Luke Mason; Ebrima Mbye; Ebou Touray; Sophie E Moore; Clare E Elwell; Sarah Lloyd-Fox; Michelle de Haan Journal: Children (Basel) Date: 2022-07-01