Genetic and Physical Characteristics of Rett Syndrome

NCT00299312 | Completed DMC

• 3 other identifiers: RDCRN 5201U54HD061222ARP 5201
• Study Type: observational
• Target: 10
• Locations: 1 country
• Sites: 11

Brief Summary

Rett Syndrome (RTT) is a genetic brain disorder that occurs almost exclusively in females and is usually caused by a change (mutation) in the gene MECP2. The disorder is characterized by multiple developmental problems, as well as behavioral features, such as repetitive stereotypic hand movements, including hand washing, wringing, and tapping. While there is no cure for RTT, recent advances in the understanding of the disease suggest that the development of new, effective therapies is promising. This study will gather information on the genetic defects that cause RTT, the physical expressions of these defects, and disease progression. In turn, this may direct the development of future treatments. Expanded studies include individuals with MECP2 Duplication disorder, and RTT-related disorders including individuals with MECP2 mutations, but not meeting obligatory criteria for the diagnosis of RTT and individuals with mutations in CDKL5 and FOXG1 some of whom meet criteria for atypical RTT.

Conditions

Rett Syndrome; MECP2 Duplication Disorder; Rett-related Disorder

Keywords

Loss of Purposeful Hand Use Syndrome; Loss of Communication; Stereotypic Hand Movements; MECP2 mutation; MECP2 duplication; CDKL5 mutation; FOXG1 mutation

Outcome Measures

Primary Outcomes (1)

• Genetic and Physical Characteristics of Rett Syndrome

  The primary endpoint is to determine the variables related to clinical outcome in terms of genotype and phenotype. The variables include growth, head circumference, stereotypic movements, periodic breathing, epilepsy, scoliosis, and longevity. Summative data are provided by the Clinical Severity Scale (CSS) and the Motor Behavioral Assessment (MBA) and specific neurophysiologic and neuroimaging studies in selected participants.

  July 31, 2019

Secondary Outcomes (1)

• Genetic and Physical Characteristics of Rett syndrome

  Through July 31, 2019

Other Outcomes (1)

• Genetic and Physical Characteristics of Rett Syndrome, MECP2 Duplication disorder, and RTT-related conditions

  July 31, 2019

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Individuals fulfilling consensus clinical criteria for Classic or Variant Rett Syndrome, individuals with MECP2 mutations who do not meet the clinical criteria, or individuals who have a duplication of Xq28 including the MECP2 locus or individuals who have mutations in CDKL5 or FOXG1.

You may qualify if:

• Meets clinical criteria for classic or variant RTT or tests positive for an MECP2 gene mutation or a MECP2 duplication or a mutation in CDKL5 or FOXG1.

You may not qualify if:

• Unwilling or unable to travel to study sites for annual or biannual evaluations

Sponsors & Collaborators

• University of Alabama at Birmingham: lead
• Rare Diseases Clinical Research Network: collaborator
• Greenwood Genetic Center: collaborator
• Baylor College of Medicine: collaborator
• Boston Children's Hospital: collaborator
• University of Rochester: collaborator
• Children's Hospital of Philadelphia: collaborator
• University of Colorado, Denver: collaborator
• Rush University Medical Center: collaborator
• UCSF Benioff Children's Hospital Oakland: collaborator
• University of California, San Diego: collaborator
• Vanderbilt University: collaborator
• University of South Florida: collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (11)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Children's Hospital of Oakland

Oakland, California, 94709, United States

Location

University of California San Diego

San Diego, California, 92123, United States

Location

University of Colorado Denver

Denver, Colorado, 80045-2571, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Children's Hospital Boston

Boston, Massachusetts, 02115, United States

Location

University of Rochester

Rochester, New York, 14627-0140, United States

Location

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania, 19104-4318, United States

Location

Greenwood Genetic Center

Greenwood, South Carolina, 29646, United States

Location

Vanderbilt University

Nashville, Tennessee, 37212, United States

Location

Baylor College of Medicine

Houston, Texas, 77030, United States

Location

Related Publications (27)

• Laccone F, Junemann I, Whatley S, Morgan R, Butler R, Huppke P, Ravine D. Large deletions of the MECP2 gene detected by gene dosage analysis in patients with Rett syndrome. Hum Mutat. 2004 Mar;23(3):234-44. doi: 10.1002/humu.20004.

  PMID: 14974082 BACKGROUND

• Schanen C, Houwink EJ, Dorrani N, Lane J, Everett R, Feng A, Cantor RM, Percy A. Phenotypic manifestations of MECP2 mutations in classical and atypical Rett syndrome. Am J Med Genet A. 2004 Apr 15;126A(2):129-40. doi: 10.1002/ajmg.a.20571.

  PMID: 15057977 BACKGROUND

• Neul JL, Fang P, Barrish J, Lane J, Caeg EB, Smith EO, Zoghbi H, Percy A, Glaze DG. Specific mutations in methyl-CpG-binding protein 2 confer different severity in Rett syndrome. Neurology. 2008 Apr 15;70(16):1313-21. doi: 10.1212/01.wnl.0000291011.54508.aa. Epub 2008 Mar 12.

  PMID: 18337588 BACKGROUND

• Bebbington A, Anderson A, Ravine D, Fyfe S, Pineda M, de Klerk N, Ben-Zeev B, Yatawara N, Percy A, Kaufmann WE, Leonard H. Investigating genotype-phenotype relationships in Rett syndrome using an international data set. Neurology. 2008 Mar 11;70(11):868-75. doi: 10.1212/01.wnl.0000304752.50773.ec.

  PMID: 18332345 BACKGROUND

• Kalman LV, Tarleton JC, Percy AK, Aradhya S, Bale S, Barker SD, Bayrak-Toydemir P, Bridges C, Buller-Burckle AM, Das S, Iyer RK, Vo TD, Zvereff VV, Toji LH. Development of a genomic DNA reference material panel for Rett syndrome (MECP2-related disorders) genetic testing. J Mol Diagn. 2014 Mar;16(2):273-9. doi: 10.1016/j.jmoldx.2013.11.004. Epub 2014 Feb 7.

  PMID: 24508304 BACKGROUND

• Leonard H, Ravikumara M, Baikie G, Naseem N, Ellaway C, Percy A, Abraham S, Geerts S, Lane J, Jones M, Bathgate K, Downs J; Telethon Institute for Child Health Research. Assessment and management of nutrition and growth in Rett syndrome. J Pediatr Gastroenterol Nutr. 2013 Oct;57(4):451-60. doi: 10.1097/MPG.0b013e31829e0b65.

  PMID: 24084372 BACKGROUND

• Percy AK. Rett syndrome: exploring the autism link. Arch Neurol. 2011 Aug;68(8):985-9. doi: 10.1001/archneurol.2011.149.

  PMID: 21825235 BACKGROUND

• Percy A. The American history of Rett syndrome. Pediatr Neurol. 2014 Jan;50(1):1-3. doi: 10.1016/j.pediatrneurol.2013.08.018. Epub 2013 Nov 5. No abstract available.

  PMID: 24200039 BACKGROUND

• Neul JL, Glaze DG, Percy AK, Feyma T, Beisang A, Dinh T, Suter B, Anagnostou E, Snape M, Horrigan J, Jones NE. Improving Treatment Trial Outcomes for Rett Syndrome: The Development of Rett-specific Anchors for the Clinical Global Impression Scale. J Child Neurol. 2015 Nov;30(13):1743-8. doi: 10.1177/0883073815579707. Epub 2015 Apr 20.

  PMID: 25895911 BACKGROUND

• Neul JL, Kaufmann WE, Glaze DG, Christodoulou J, Clarke AJ, Bahi-Buisson N, Leonard H, Bailey ME, Schanen NC, Zappella M, Renieri A, Huppke P, Percy AK; RettSearch Consortium. Rett syndrome: revised diagnostic criteria and nomenclature. Ann Neurol. 2010 Dec;68(6):944-50. doi: 10.1002/ana.22124.

  PMID: 21154482 RESULT

• Percy AK, Neul JL, Glaze DG, Motil KJ, Skinner SA, Khwaja O, Lee HS, Lane JB, Barrish JO, Annese F, McNair L, Graham J, Barnes K. Rett syndrome diagnostic criteria: lessons from the Natural History Study. Ann Neurol. 2010 Dec;68(6):951-5. doi: 10.1002/ana.22154.

  PMID: 21104896 RESULT

• Percy AK, Lee HS, Neul JL, Lane JB, Skinner SA, Geerts SP, Annese F, Graham J, McNair L, Motil KJ, Barrish JO, Glaze DG. Profiling scoliosis in Rett syndrome. Pediatr Res. 2010 Apr;67(4):435-9. doi: 10.1203/PDR.0b013e3181d0187f.

  PMID: 20032810 RESULT

• Glaze DG, Percy AK, Skinner S, Motil KJ, Neul JL, Barrish JO, Lane JB, Geerts SP, Annese F, Graham J, McNair L, Lee HS. Epilepsy and the natural history of Rett syndrome. Neurology. 2010 Mar 16;74(11):909-12. doi: 10.1212/WNL.0b013e3181d6b852.

  PMID: 20231667 RESULT

• Kirby RS, Lane JB, Childers J, Skinner SA, Annese F, Barrish JO, Glaze DG, Macleod P, Percy AK. Longevity in Rett syndrome: analysis of the North American Database. J Pediatr. 2010 Jan;156(1):135-138.e1. doi: 10.1016/j.jpeds.2009.07.015.

  PMID: 19772971 RESULT

• McCauley MD, Wang T, Mike E, Herrera J, Beavers DL, Huang TW, Ward CS, Skinner S, Percy AK, Glaze DG, Wehrens XH, Neul JL. Pathogenesis of lethal cardiac arrhythmias in Mecp2 mutant mice: implication for therapy in Rett syndrome. Sci Transl Med. 2011 Dec 14;3(113):113ra125. doi: 10.1126/scitranslmed.3002982.

  PMID: 22174313 RESULT

• Motil KJ, Caeg E, Barrish JO, Geerts S, Lane JB, Percy AK, Annese F, McNair L, Skinner SA, Lee HS, Neul JL, Glaze DG. Gastrointestinal and nutritional problems occur frequently throughout life in girls and women with Rett syndrome. J Pediatr Gastroenterol Nutr. 2012 Sep;55(3):292-8. doi: 10.1097/MPG.0b013e31824b6159.

  PMID: 22331013 RESULT

• Bebbington A, Downs J, Percy A, Pineda M, Zeev BB, Bahi-Buisson N, Leonard H. The phenotype associated with a large deletion on MECP2. Eur J Hum Genet. 2012 Sep;20(9):921-7. doi: 10.1038/ejhg.2012.34. Epub 2012 Apr 4.

  PMID: 22473088 RESULT

• Bebbington A, Percy A, Christodoulou J, Ravine D, Ho G, Jacoby P, Anderson A, Pineda M, Ben Zeev B, Bahi-Buisson N, Smeets E, Leonard H. Updating the profile of C-terminal MECP2 deletions in Rett syndrome. J Med Genet. 2010 Apr;47(4):242-8. doi: 10.1136/jmg.2009.072553. Epub 2009 Nov 12.

  PMID: 19914908 RESULT

• Tarquinio DC, Motil KJ, Hou W, Lee HS, Glaze DG, Skinner SA, Neul JL, Annese F, McNair L, Barrish JO, Geerts SP, Lane JB, Percy AK. Growth failure and outcome in Rett syndrome: specific growth references. Neurology. 2012 Oct 16;79(16):1653-61. doi: 10.1212/WNL.0b013e31826e9a70. Epub 2012 Oct 3.

  PMID: 23035069 RESULT

• Motil KJ, Barrish JO, Lane J, Geerts SP, Annese F, McNair L, Percy AK, Skinner SA, Neul JL, Glaze DG. Vitamin D deficiency is prevalent in girls and women with Rett syndrome. J Pediatr Gastroenterol Nutr. 2011 Nov;53(5):569-74. doi: 10.1097/MPG.0b013e3182267a66.

  PMID: 21637127 RESULT

• Lane JB, Lee HS, Smith LW, Cheng P, Percy AK, Glaze DG, Neul JL, Motil KJ, Barrish JO, Skinner SA, Annese F, McNair L, Graham J, Khwaja O, Barnes K, Krischer JP. Clinical severity and quality of life in children and adolescents with Rett syndrome. Neurology. 2011 Nov 15;77(20):1812-8. doi: 10.1212/WNL.0b013e3182377dd2. Epub 2011 Oct 19.

  PMID: 22013176 RESULT

• Chapleau CA, Lane J, Kirwin SM, Schanen C, Vinette KM, Stubbolo D, MacLeod P, Glaze DG, Motil KJ, Neul JL, Skinner SA, Kaufmann WE, Percy AK. Detection of rarely identified multiple mutations in MECP2 gene do not contribute to enhanced severity in Rett syndrome. Am J Med Genet A. 2013 Jul;161A(7):1638-46. doi: 10.1002/ajmg.a.35979. Epub 2013 May 21.

  PMID: 23696494 RESULT

• Cuddapah VA, Pillai RB, Shekar KV, Lane JB, Motil KJ, Skinner SA, Tarquinio DC, Glaze DG, McGwin G, Kaufmann WE, Percy AK, Neul JL, Olsen ML. Methyl-CpG-binding protein 2 (MECP2) mutation type is associated with disease severity in Rett syndrome. J Med Genet. 2014 Mar;51(3):152-8. doi: 10.1136/jmedgenet-2013-102113. Epub 2014 Jan 7.

  PMID: 24399845 RESULT

• Neul JL, Lane JB, Lee HS, Geerts S, Barrish JO, Annese F, Baggett LM, Barnes K, Skinner SA, Motil KJ, Glaze DG, Kaufmann WE, Percy AK. Developmental delay in Rett syndrome: data from the natural history study. J Neurodev Disord. 2014;6(1):20. doi: 10.1186/1866-1955-6-20. Epub 2014 Jul 22.

  PMID: 25071871 RESULT

• Killian JT, Lane JB, Cutter GR, Skinner SA, Kaufmann WE, Tarquinio DC, Glaze DG, Motil KJ, Neul JL, Percy AK. Pubertal development in Rett syndrome deviates from typical females. Pediatr Neurol. 2014 Dec;51(6):769-75. doi: 10.1016/j.pediatrneurol.2014.08.013. Epub 2014 Aug 29.

  PMID: 25283752 RESULT

• Tarquinio DC, Hou W, Neul JL, Lane JB, Barnes KV, O'Leary HM, Bruck NM, Kaufmann WE, Motil KJ, Glaze DG, Skinner SA, Annese F, Baggett L, Barrish JO, Geerts SP, Percy AK. Age of diagnosis in Rett syndrome: patterns of recognition among diagnosticians and risk factors for late diagnosis. Pediatr Neurol. 2015 Jun;52(6):585-91.e2. doi: 10.1016/j.pediatrneurol.2015.02.007. Epub 2015 Feb 16.

  PMID: 25801175 RESULT

• Buchanan CB, Stallworth JL, Joy AE, Dixon RE, Scott AE, Beisang AA, Benke TA, Glaze DG, Haas RH, Heydemann PT, Jones MD, Lane JB, Lieberman DN, Marsh ED, Neul JL, Peters SU, Ryther RC, Skinner SA, Standridge SM, Kaufmann WE, Percy AK. Anxiety-like behavior and anxiolytic treatment in the Rett syndrome natural history study. J Neurodev Disord. 2022 May 14;14(1):31. doi: 10.1186/s11689-022-09432-2.

  PMID: 35568815 DERIVED

Related Links

• Click here for the International Rett Syndrome Foundation website

MeSH Terms

Conditions

Rett Syndrome

Condition Hierarchy (Ancestors)

X-Linked Intellectual Disability; Intellectual Disability; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Heredodegenerative Disorders, Nervous System

Study Officials

• Alan K Percy, MD

  University of Alabama at Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Pediatrics, Neurolgy, Neurobiology, Genetics

Study Record Dates

• First Submitted: March 3, 2006
• First Posted: March 6, 2006
• Study Start: March 1, 2006
• Primary Completion: October 1, 2015
• Study Completion: October 1, 2015
• Last Updated: March 16, 2017

Record last verified: 2017-03

Locations

US (11)