Fragile X syndrome
Fragile X

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Description from OMIM

Fragile X mental retardation is characterized by moderate to severe mental retardation, macroorchidism, and distinct facial features, including long face, large ears, and prominent jaw. In most cases, the disorder is caused by the unstable expansion of a CGG repeat in the FMR1 gene and abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain (Devys et al., 1993). Reviews Fragile X syndrome accounts for about one-half of cases of X-linked mental retardation and is the second most common cause of mental impairment after trisomy 21 (190685) (Rousseau et al., 1995). McCabe et al. (1999) summarized the proceedings of a workshop on the fragile X syndrome held in December 1998. Jacquemont et al. (2007) provided a review of fragile X syndrome, which they characterized as a neurodevelopmental disorder, and FXTAS, which they characterized as a neurodegenerative disorder.

Prevalence of clinical parameters (%)

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List of symptoms

Symptom/sign Organ system Percent affected Pubmed id Added on(yyyy-mm-dd) Edit/add reference
Mental retardation nervous 100 % 12418611 2011-10-19
Hypermobile joints skeletal 57 % 2195034 2011-10-06
Pes planus skeletal 50 % 2195034 2011-10-06
Autism nervous 32 % 21527394 2011-10-06
Seizures nervous 13 % 12418611 2011-10-06
Scoliosis skeletal 7 % 2195034 2011-10-06
Seizures nervous 7 % 17932962 2011-10-06

List of references:

Epilepsy in fragile X syndrome.
Elizabeth Berry-Kravis,

Epilepsy is reported to occur in 10 to 20% of individuals with fragile X syndrome (FXS). A frequent seizure/EEG pattern in FXS appears to resemble that of benign focal epilepsy of childhood (BFEC, benign rolandic epilepsy). To evaluate seizure frequency and type in a Chicago FXS cohort, data regarding potential seizure history were reviewed for 136 individuals with FXS (age range 2 to 51 years: 113 males and 23 females). Seizures occurred in 15 males (13.3%) and one female (4.8%): of these, 12 had partial seizures. EEG findings were available for 35 individuals (13 of 16 with seizures and 22 of 120 without seizures) and showed an epileptiform abnormality in 10 (77%) individuals with seizures and five (23%) individuals without seizures--the most common epileptiform pattern being centrotemporal spikes. Seizures were easily controlled in 14 of the 16 individuals with seizures. Many individuals, including all with centrotemporal spikes, had remission of seizures in childhood. The most common seizure syndrome resembled BFEC and this pattern had the best prognosis for epilepsy remission. Deficiency of FMRP (fragile X mental retardation protein) appears to lead to increased neuronal excitability and susceptibility to epilepsy, but particularly seems to facilitate mechanisms leading to the BFEC pattern.

Developmental medicine and child neurology - Nov 2002

Orthopaedic aspects of fragile-X syndrome.
J R Davids, R J Hagerman, R E Eilert,

Fragile-X syndrome is one of the most common inherited forms of mental retardation. An associated connective-tissue disorder involving elastin accounts for the most frequent musculoskeletal manifestations, which include severe flexible flat feet, excessive laxity of the joints, and scoliosis. At our institution, seventy-five (50 per cent) of the 150 male patients who had fragile-X syndrome had flat feet, eighty-five (57 per cent) had excessive laxity of the joints, and ten had scoliosis. Twenty-nine of the patients who had flat feet had been evaluated or treated, or both, by an orthopaedic surgeon before the diagnosis of fragile-X syndrome had been made. Only one of these patients had been referred for developmental and genetic evaluation, which suggests that the orthopaedic community is not familiar with this syndrome. The orthopaedist should consider the diagnosis of fragile-X syndrome in the evaluation of a mentally retarded boy or man who has a family history of mental retardation. The presence of flat feet and excessive laxity of the joints, associated with the characteristic facies, macro-orchidism, and behavior, justifies a referral for developmental and genetic evaluation. Early diagnosis is important for several reasons, including genetic counseling for the family, more efficacious medical treatment, and specialized education.

The Journal of bone and joint surgery. American volume - Jul 1990

Psychiatric and autistic comorbidity in fragile X syndrome across ages.
Lidia V Gabis, Yael Kesner Baruch, Ariela Jokel, Raanan Raz,

Fragile X syndrome is caused by CGG trinucleotide repeat expansion within the fragile X mental retardation 1 gene, when repeat number exceeds 200. The typical psychiatric profile of fragile X syndrome patients includes cognitive and behavioral deficits, psychiatric comorbidity, and autistic characteristics. Specific psychiatric features have not yet been clarified, specifically in relationship to age and genetic characteristics. The objective of this study was to characterize psychiatric comorbidities in subjects with fragile X syndrome at different ages. Subjects with fragile X syndrome and their unaffected siblings were recruited and their parents filled out functional-behavioral and psychiatric comorbidities questionnaires. Adolescents with fragile X syndrome showed decreased prevalence of functional-behavioral deficits. Incidence and severity of most psychiatric comorbidities were lower in older subjects. Incidence of generalized anxiety disorder increased with age in the fragile X syndrome group. The typical profile of patients with fragile X syndrome changes with age. Unaffected siblings exhibit anxiety and motor tics.

Journal of child neurology - Aug 2011

Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP).
Doron Gothelf, Joyce A Furfaro, Fumiko Hoeft, Mark A Eckert, Scott S Hall, Ruth O'Hara, Heather W Erba, Jessica Ringel, Kiralee M Hayashi, Swetapadma Patnaik, Brenda Golianu, Helena C Kraemer, Paul M Thompson, Joseph Piven, Allan L Reiss,

To determine how neuroanatomic variation in children and adolescents with fragile X syndrome is linked to reduced levels of the fragile X mental retardation-1 protein and to aberrant cognition and behavior.

Annals of neurology - Jan 2008