Health Supervision for Children With Fragile X Syndrome

Abstract

Fragile X syndrome (an FMR1–related disorder) is the most commonly inherited form of mental retardation. Early physical recognition is difficult, so boys with developmental delay should be strongly considered for molecular testing. The characteristic adult phenotype usually does not develop until the second decade of life. Girls can also be affected with developmental delay. Because multiple family members can be affected with mental retardation and other conditions (premature ovarian failure and tremor/ataxia), family history information is of critical importance for the diagnosis and management of affected patients and their families. This report summarizes issues for fragile X syndrome regarding clinical diagnosis, laboratory diagnosis, genetic counseling, related health problems, behavior management, and age-related health supervision guidelines. The diagnosis of fragile X syndrome not only involves the affected children but also potentially has significant health consequences for multiple generations in each family.

Fragile X Syndrome: A Review of Associated Medical Problems

“…2 This review of associated medical problems presents, for the first time, estimates of the prevalence of selected conditions from a large comprehensive database of children with FXS attending clinics across the United States. Although the nature of Fragile X Clinic attendance could make the FXCRC Database limited in providing the true range of severity of medical problems in FXS, it may allow the identification of at least moderate to severe ones, problems that are likely to come to medical attention.…”

“…1,2 It results from an expansion mutation of a CGG repeat sequence in the first exon of the FMR1 gene, leading to transcriptional silencing of the gene and absence or significant reduction of the gene product, fragile X mental retardation protein. 3,4 This protein is essential for proper synaptic plasticity, neuronal morphology, and cognitive development, and its absence leads to varying levels of ID.…”

“…6 In addition to ID, there are particular phenotypic characteristics of FXS that may be variably present, including prominent forehead, narrow face, protruding ears, high-arched palate, strabismus, macro-orchidism, and connective tissue dysplasia including hyperflexibility of the joints. 2,7,8 In clinical settings, patients with FXS may be seen for a variety of medical problems related to FXS including seizures, recurrent otitis media (OM), and gastrointestinal (GI) disturbances. It has been hypothesized that some of these, such as OM and gastroesophageal reflux (GER), may be related to connective tissue abnormalities.…”

A Quality Improvement Collaborative to Improve Pediatric Primary Care Genetic Services

“…[10][11][12] Additionally, many pediatricians report the inconsistent application of best-practice recommendations for a cornerstone of genetic disease assessment: creating family histories. 7,[12][13][14][15] Finally, although many genetic conditions have specific health supervision guidelines, [16][17][18][19][20][21][22][23][24] it is unclear how often these guidelines are followed by pediatricians or how best to ensure guideline implementation.…”

“…Adherence with 4 of the 7 aims had significant improvements comparing baseline to the end of the active improvement period using the fit of the random intercept binomial regression models: "family histories are created/maintained at health supervision visits documenting all components" (6% vs 60%, P < .001), "patients with genetic disorders have up to date age-appropriate health supervision visits" (70% vs 77%, P < .001), "patients with specific genetic disorders that have existing disorder-specific health supervision guidelines [16][17][18][19][20][21][22][23][24] receive the specified care" (58% vs 85%, P < .001), and "patients with genetic disorders have next steps of care and planned follow-up" (14% vs 47%, P < .001; Table 3). All of these aims also demonstrated statistically significant improvements in adherence using the fit of the random intercept binomial regression models comparing the end of the active improvement period to the end of the sustainability period, suggesting improvements were sustained and even increased.…”