Fragile X syndrome: A review of clinical management.
The fragile X mental retardation 1 gene, which codes for the fragile X mental retardation 1 protein, usually has 5 to 40 CGG repeats in the 5' untranslated promoter. The full mutation is the almost always the cause of fragile X syndrome (FXS). The prevalence of FXS is about 1 in 4,000 to 1 in 7,000 in the general population although the prevalence varies in different regions of the world. FXS is the most common inherited cause of intellectual disability and autism. The understanding of the neurobiology of FXS has led to many targeted treatments, but none have cured this disorder. The treatment of the medical problems and associated behaviors remain the most useful intervention for children with FXS. In this review, we focus on the non-pharmacological and pharmacological management of medical and behavioral problems associated with FXS as well as current recommendations for follow-up and surveillance.
Medical Investigation of Neurodevelopmental Disorders MIND Institute, UC Davis, CA, USA; Department of Pediatrics, UC Davis, Sacramento, CA, USA.
Reymundo
R
Lozano
Medical Investigation of Neurodevelopmental Disorders MIND Institute, UC Davis, CA, USA; Department of Pediatrics, UC Davis, Sacramento, CA, USA.
Atoosa
A
Azarang
Medical Investigation of Neurodevelopmental Disorders MIND Institute, UC Davis, CA, USA; Department of Pediatrics, UC Davis, Sacramento, CA, USA.
Tanaporn
T
Wilaisakditipakorn
Medical Investigation of Neurodevelopmental Disorders MIND Institute, UC Davis, CA, USA; Department of Pediatrics, UC Davis, Sacramento, CA, USA.
Randi J
RJ
Hagerman
Autism Spectrum Disorder; FMR1; FMRP; Fragile X syndrome; Intellectual Disability; clinical guidelines; clinical management; developmental delay; medical problems; premutation; treatment
Am Fam Physician. 1999 Apr 15;59(8):2263-72, 2274
10221310
Curr Opin Neurol. 1998 Aug;11(4):373-80
9725084
Epilepsia. 1999 Aug;40(8):1092-9
10448821
J Pediatr. 1980 May;96(5):837-41
7189210
Pediatrics. 2000 Sep;106(3):483-8
10969091
Sleep. 2000 Dec 15;23(8):1043-51
11145319
Pediatrics. 2012 Sep;130(3):e714-55
22926176
J Am Optom Assoc. 1990 Apr;61(4):316-23
2189924
Neurotherapeutics. 2015 Jul;12(3):584-608
25986746
Pediatr Surg Int. 2011 Apr;27(4):353-8
20697898
Am J Med Genet. 1984 Jan;17(1):123-31
6711591
Intractable Rare Dis Res. 2014 Nov;3(4):134-46
25606363
Am J Med Genet. 2000 Dec 11;95(4):307-15
11186882
Neuron. 2010 Feb 11;65(3):385-98
20159451
Colomb Med (Cali). 2014 Dec 30;45(4):190-8
25767309
Eur J Neurosci. 2007 Dec;26(11):3169-80
18005058
Sleep Med. 2009 Aug;10(7):771-9
19285450
Proc Natl Acad Sci U S A. 1997 May 13;94(10):5401-4
9144249
J Clin Sleep Med. 2009 Apr 15;5(2):145-50
19968048
Am J Med Genet. 1988 May-Jun;30(1-2):83-98
2972207
Rev Prat. 2014 Nov;64(9):1195-202
25638852
Cochrane Database Syst Rev. 2011 Nov 09;(11):CD007095
22071833
Am J Intellect Dev Disabil. 2009 Nov;114(6):383-92
19792059
Optom Vis Sci. 1991 Aug;68(8):634-40
1923341
Lancet. 1998 Apr 25;351(9111):1254
9643754
J Pediatr. 1981 Aug;99(2):197-201
7252674
Am J Med Genet. 1995 Sep 11;58(3):249-56
8533827
J AAPOS. 1998 Oct;2(5):298-302
10646752
J AAPOS. 2015 Aug;19(4):298-303
26235788
Prenat Diagn. 1984 Jan-Feb;4(1):61-6
6728827
Pediatrics. 2002 Feb;109(2):351-2; author reply 353
11826228
Am J Med Genet. 1992 Apr 15-May 1;43(1-2):124-7
1605180
Hum Genet. 1983;63(2):139-48
6840758
J Am Dent Assoc. 2007 Jun;138(6):739-45, 747-60
17545263
J Pediatr. 2000 Sep;137(3):321-6
10969254
Pediatrics. 1993 May;91(5):867-72
8474804
Curr Genomics. 2011 May;12(3):216-24
22043169
Laryngoscope. 1980 Oct;90(10 Pt 1):1709-16
7421381
Curr Opin Pediatr. 1994 Dec;6(6):712-6
7849820
Epilepsia. 2014 Apr;55(4):496-506
24597466
Br Heart J. 1989 Mar;61(3):289-91
2930667
Profiles Drug Subst Excip Relat Methodol. 2016;41:133-321
26940169
J Neurodev Disord. 2014;6(1):24
25110527
Sleep Med. 2013 Dec;14(12):1290-4
24157098
J Med Genet. 1995 Oct;32(10):764-9
8558551
Am J Med Genet. 1988 May-Jun;30(1-2):123-42
3177438
J Neurodev Disord. 2010 Jun;2(2):62-9
22127855
Am J Med Genet. 1997 Oct 17;72 (2):156-8
9382135
Brain Dev. 2002 Dec;24(8):766-9
12453600
Hum Genet. 1981;59(4):281-9
7333582
Am J Dis Child. 1987 Feb;141(2):184-7
3812386
Am J Med Genet A. 2010 Jun;152A(6):1420-7
20503316
J Hum Genet. 2013 Jun;58(6):317-26
23635947
PLoS One. 2014 Mar 12;9(3):e80488
24622158
Eur J Hum Genet. 2008 Jun;16(6):666-72
18398441
Sleep. 1992 Dec;15(6 Suppl):S17-9
1470802
J Neurodev Disord. 2011 Mar;3(1):57-67
21475730
Otolaryngol Head Neck Surg. 2006 Jun;134(6):979-84
16730542
Birth Defects Orig Artic Ser. 1987;23(1):103-14
3580542
Lancet. 2005 Feb 5-11;365(9458):507-18
15705461
Pediatrics. 1992 Aug;90(2 Pt 1):228-32
1641287
Am J Intellect Dev Disabil. 2009 Jul;114(4):289-303
19642710
Am J Hum Genet. 1996 May;58(5):1025-32
8651263
Am J Psychiatry. 2014 Oct;171(10):1099-106
24969119
Pediatrics. 2014 Nov;134(5):995-1005
25287458
J AAPOS. 2012 Apr;16(2):182-4
22525177
Pediatrics. 1992 Mar;89(3):395-400
1741210
Am J Med Genet. 1999 Apr 2;83(4):268-79
10208160
Pediatr Infect Dis J. 2000 May;19(5 Suppl):S31-6
10821470
Am J Med Genet A. 2013 Dec;161A(12):2989-3004
24254847
J Clin Psychiatry. 2014 Apr;75(4):e294-307
24813413
Pediatrics. 1997 Jun;99(6):E5
9164801
Cold Spring Harb Perspect Biol. 2012 Aug 01;4(8):a012344
22723494
Dev Med Child Neurol. 2002 Nov;44(11):724-8
12418611
J Dev Behav Pediatr. 2007 Apr;28(2):133-8
17435464
J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(8):947-68
17667475
Am J Med Genet B Neuropsychiatr Genet. 2011 Dec;156B(8):923-8
21932336
Am J Med Genet. 1988 May-Jun;30(1-2):207-12
3177446
Trends Neurosci. 2007 Aug;30(8):425-31
17590448
Pediatrics. 2009 Jan;123(1):378-90
19117905
Am J Med Genet. 1984 Jan;17(1):175-94
6711594
J Neurodev Disord. 2011 Sep;3(3):193-210
21484200
Results Probl Cell Differ. 2012;54:297-335
22009360
Epilepsia. 2000 Jan;41(1):19-23
10643918
Prenat Diagn. 2009 Jan;29(1):57-61
19097038
Genet Med. 2008 Jan;10(1):4-12
18197051
Pediatrics. 1992 Jun;89(6 Pt 1):1059-62
1594348
Drugs. 2001;61(15):2207-20
11772131
Eur J Paediatr Neurol. 2016 Sep;20(5):696-703
27228790
Neurol Clin. 1997 May;15(2):267-75
9115460
J Intellect Disabil Res. 2007 Feb;51(Pt 2):151-61
17217479
Reprod Biomed Online. 2007 Apr;14(4):515-21
17425837
Br J Gen Pract. 2008 May;58(550):364-5
18482495
Neurosci Lett. 2015 Jan 12;585:109-13
25433180
Ment Retard Dev Disabil Res Rev. 2000;6(3):186-97
10982496
Science. 1991 May 24;252(5009):1097-102
2031184
Pharmacogenet Genomics. 2013 Apr;23(4):236-41
23407051
Sleep. 2010 May;33(5):679-87
20469810
Dev Med Child Neurol. 2004 Nov;46(11):776-82
15540640
J Neurodev Disord. 2010 Jun;2(2):70-76
20585378
Genet Med. 2001 May-Jun;3(3):200-5
11388762
Arch Dis Child. 1985 Nov;60(11):1001-7
4073931
Genet Med. 2010 Mar;12(3):162-73
20168238
J Neurol Neurosurg Psychiatry. 1985 Feb;48(2):150-3
3920355
Am J Med Genet. 1986 Jan-Feb;23(1-2):189-94
3953647
Acta Paediatr. 1995 Jul;84(7):791-4
7549299
Pediatrics. 2013 Mar;131(3):e964-99
23439909
J Pineal Res. 2009 Mar;46(2):224-34
19141086
Arch Otolaryngol Head Neck Surg. 1999 Jul;125(7):758-62
10406313
Am J Intellect Dev Disabil. 2010 Nov;115(6):461-72
20945999
Am J Med Genet. 1980;7(4):471-89
7211957
Int J Pediatr Otorhinolaryngol. 2000 Aug 11;54(1):13-20
10960691
J Child Neurol. 2001 Aug;16(8):581-4
11510929
Epilepsy Curr. 2009 Jul-Aug;9(4):108-12
19693328
Pediatrics. 1993 Apr;91(4):714-5
8464655
Pediatr Neurol. 1996 Nov;15(4):358-60
8972540
Dev Med Child Neurol. 1987 Dec;29(6):734-42
2961643
Pediatrics. 1999 Jun;103(6 Pt 2):1359-68
10353954
Sleep Med Rev. 2015 Oct;23 :28-45
25645128
Hum Genet. 2010 Nov;128(5):539-48
20809278
Dev Med Child Neurol. 1999 Jul;41(7):491-500
10454235
Am J Med Genet A. 2003 Apr 15;118A(2):127-34
12655493
Obstet Gynecol. 2010 Oct;116(4):1008-10
20859177
Am J Med Genet A. 2012 Oct;158A(10):2473-81
22903889
Meta Gene. 2014 Jan 14;2:96-105
25606393
Am J Hum Genet. 1969 May;21(3):231-44
5794013
Can J Neurol Sci. 1987 Aug;14(3 Suppl):541-6
2890426
Neuropsychiatr Dis Treat. 2014 Sep 16;10:1769-79
25258535
Am J Med Genet. 1988 May-Jun;30(1-2):143-7
3177439
Pediatrics. 1997 Oct;100(4):E7
9310540
J Am Acad Child Adolesc Psychiatry. 2012 Sep;51(9):921-33
22917205
Cell. 1991 May 31;65(5):905-14
1710175
Eur J Ophthalmol. 2003 Jul;13(6):566-74
12948316
Am J Med Genet A. 2008 Aug 1;146A(15):1911-6
18627038
J Neurol. 2006 Jan;253(1):1-15
16331353
Psychoneuroendocrinology. 2014 Nov;49:119-29
25080404
J Pediatr (Rio J). 2008 Jan-Feb;84(1):9-17
18264618
J Emerg Med. 1993 Jul-Aug;11(4):475-8
8080481
Neurourol Urodyn. 2013 Sep;32(7):986-92
23239431
Otolaryngol Head Neck Surg. 2013 Apr;148(4 Suppl):E1-E25
23536527
Am J Dis Child. 1993 Jun;147(6):605-7
8506819