Various Researches on Fragile X Syndrome and its Associated Medical Problems

Medical problems and their management in Fragile X syndrome population

This paper focuses on the fragile X syndrome and the associated medical and behavioral problems among the children population.  Some of the medical problems discussed include Otitis media, Seizures, Mitral Valve Prolapse, Sleep and others. The authors have discussed about the pharmacological and non- pharmacological management of these problems and have given recommendations for surveillance. The research has deeply analyzed the medical problems and has included its preventive measures and treatment benefits. It could have also included the side effects of the treatment and the duration of the treatment. This paper is suitable for our research (Lozano, Azarang, Wilaisakditipakorn, & Hagerman, 2016).

In this research, Brown and Stanfield have reviewed the neuroimaging findings of the permutation of the Fragile X-associated Tremor or Ataxia Syndrome (FXTAS) especially through maternal transmission. The authors have discussed the clinical findings, molecular measurements, and structural image findings that target the cause of the permutation of the fragile X syndrome and have also explained a correlation between these findings. The limitation in the paper is the narrow research on techniques and methods of analysis based on only 3 databases. The paper is helpful as it enlightens the cause and effect of manifestation and permutation of the fragile X through methodology of functional MRI reports (Brown & Stanfield, 2015).

The research paper focuses on the phenotypic heterogeneity and clinical research implications of fragile X syndrome. The new therapy trials for FXS in patients have pinpointed certain challenges of heterogeneity, drug response and lack of reliable biomarkers. The research discusses the importance of considerate and careful selection of appropriate patients with various molecular etiologies for future trials of the modifying disease.  The paper is useful for our research as it talks about the development of clinical trial designs by strategic patient selection and personalized therapeutic interventions to optimize the clinical outcomes (Jacquemont, et al., 2014).                                  

O’Keefe, J. A., Robertson-Dick, E., Dunn, E. J., Li, Y., Deng, Y., Fiutko, A. N., et al. (2015). Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). The Cerebellum, 14(6), 650-662.doi: 10.1007/s12311-015-0659-7

In this paper the authors have discussed about the Fragile X Tremor or Ataxia Syndrome (FXTAS) that is caused due to fragile X permutation of CGG, size 55-200 and growth of fragile X mental retardation 1 gene. The methodology of Computerized Dynamic Post urography (CDP) and performance measures of fall risk and functional mobility were used to analyze 44 subject per-mutants, 21 with and 23 without FXTAS. The study concluded that the male, old age, and women with lower X activation of FMRI carriers performed worst on the CDP scale. The limitation is the scale of carriers analyzed (only 44). The paper is relevant as it suggests preclinical signs that should be detected early for interventions and treatment strategies (O’Keefe, et al., 2015).

Neuroimaging findings of the Fragile X-associated Tremor or Ataxia Syndrome (FXTAS)

The study evaluates the reliability of the gender neutral molecular screen for rapid FXS detection on dried blood spots of DNA cells. The study focused on 151 disabled or autistic FXS carriers and the methodology of TP-PCR (Triplet Primed PCR) and MCA (Melt Curve Analysis) test were used for the analysis. The study concluded that using TP-PCR MCA of the    dried blood spot was a suitable strategy for screening first-tier high throughput screening for FXS. The potential shortcoming of the research is the non-inclusion of any financial or commercial relationship (Tan, Lian, Faradz, Winarni, & Chong, 2018).

Kraan, Godler and Amor have focused on discussion of new testing techniques and methods to detect FXS in children and other additional cases. The paper also discusses improvised analysis of DNA methylation for better FXS assessment. The authors have reviewed the implication and advancement in the underlying FXS genetic and epigenetic processes for treatment of FMR-1 disorders in individuals. The tests discussed in the paper are beneficial to predict long-term prognosis and can be used on infants for screening. The study is useful for us as it helps to understand the importance of development of epigenetic therapies for FXS detection, However it lacks in large scale analysis (Kraan, Godler, & Amor, 2019).

The research paper had discussed the reliability and feasibility of chimeric primer assay for New Born Screening (NBS) of FXS, using fragile X pilot study on 2000 new born in Australia. The authors even provided insight on the protocol and procedure for the diagnostic testing and screening. The outcomes of the paper concluded that the screening test was not feasible enough to implement the test as a routine as the cost per head was too high and hence, declared the test as a two-tier assay for FMRP (Fragile X Mental Retardation Protein). The paper helps us as it makes a suggestion to use alternative strategy for cost effective testing (Wotton, et al., 2018).

This article focuses on evaluating the parent-delivered Early Start Denver Model (P-ESDM), which is an autism intervention model for children with FXS. The authors implemented parent-coaching model on 4 parent-child dyads who had taken part in the study trials. The study is useful for us as it helps to observe the behavior of ASD patients with FXS and provides techniques for parents and society to communicate and socialize with the young patients for their effective treatment. However the study is not much reliable as the study engaged with very small sample size with baseline data, and also failed to provide any comparisons (Vismara, McCormick, Shields, & Hessl, 2019).

Phenotypic heterogeneity and clinical research implications of Fragile X syndrome

The authors have analyzed and evaluated the use of Metformin drug in treatment of young age group of children diagnosed with FXS. The study examined 9 young children belonging to age group 2-7 with FXS who were treated with Metformin and concluded using pre and post developmental test reports and parents feedback that the children displayed improved changes in language, hyper activeness, behavior and social responsiveness. Hence with this study supports our work by giving us insights of using Metformin for targeted treatment of cognitive and behavioral problems related with FXS. The setback was non-inclusion of any defined protocol and a controlled limited trial of the study (Biag, et al., 2019).

The article has focused on the study of the impact of FXS on different sex (male and female). Different scales like Social Responsiveness Scale-2, Vineland Adaptive Behavior Scales etc. were used in the study to determine cognitive, academic, adaptive and functional skills among 21 girl child participants between age group of 6-14 and correlation between the behavior and skills were evaluated. This study is helpful as it tells us that cognitive ability does not play any primary role to determine the functional outcomes for FXS girl patients. Hence, the authors have emphasized the need to conduct more research on the vulnerable female population that deals with the genetic condition of FXS (Bartholomay, Lee, Bruno, Lightbody, & Reiss, 2019).

Bartholomay, K., Lee, C., Bruno, J., Lightbody, A., & Reiss, A. (2019). Closing the Gender Gap in Fragile X Syndrome: Review of Females with Fragile X Syndrome and Preliminary Research Findings. Brain Sciences, 9(1), 11. doi:.3390/brainsci9010011

Biag, H. M., Potter, L. A., Wilkins, V., Afzal, S., Rosvall, A., Salcedo-Arellano, M. J., et al. (2019). Metformin treatment in young children with fragile X syndrome. Molecular Genetics & Genomic Medicine, 7(11), e956. https://doi.org/10.1002/mgg3.956

Brown, S. S., & Stanfield, A. C. (2015). Fragile X premutation carriers: A systematic review of neuroimaging findings. Journal of the Neurological Sciences, 352(1-2), 19-28.doi: 10.1016/j.jns.2015.03.031

Jacquemont, S., Berry-Kravis, E., Hagerman, R., Raison, F. v., Gasparini, F., Apostol, G., et al. (2014). The challenges of clinical trials in fragile X syndrome. Psychopharmacology, 231, 1237–1250.doi: 10.1007/s00213-013-3289-0

Kraan, C. M., Godler, D. E., & Amor, D. J. (2019). Epigenetics of fragile X syndrome and fragile X-related disorders. Developmental Medicine and Child Neurology, 61(2), 121-127.doi: 10.1111/dmcn.13985

Lozano, R., Azarang, A., Wilaisakditipakorn, T., & Hagerman, R. J. (2016). Fragile X Syndrome: A Review Of Clinical Management. Intractable & Rare Diseases Research, 5(3), 145-157. doi: 10.5582/irdr.2016.01048

O’Keefe, J. A., Robertson-Dick, E., Dunn, E. J., Li, Y., Deng, Y., Fiutko, A. N., et al. (2015). Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). The Cerebellum, 14(6), 650-662.doi: 10.1007/s12311-015-0659-7

Tan, V. J., Lian, M., Faradz, S. M., Winarni, T. I., & Chong, S. S. (2018). A Single Common Assay for Robust and Rapid Fragile X Mental Retardation Syndrome Screening From Dried Blood Spots. Frontiers in Genetics, 9. https://doi.org/10.3389/fgene.2018.00582

Vismara, L. A., McCormick, C. E., Shields, R., & Hessl, D. (2019). Extending the Parent-Delivered Early Start Denver Model to Young Children with Fragile X Syndrome. Journal of Autism and Developmental Disorders, 49, 1250–1266. doi: 10.1007/s10803-018-3833-1

Wotton, T., Wiley, V., Bennetts, B., Christie, L., Wilcken, B., Jenkins, G., et al. (2018). Are We Ready for Fragile X Newborn Screening Testing?—Lessons Learnt from a Feasibility Study. International Journal of Neonatal Screening, 4(1), 9.doi: 10.3390/ijns4010009

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