.png){kind=small}
Abstract
Rare pediatric genetic disease are frequently complex and dangerous. Genetic disease are primarily brought on by abnormalities in DNA. Rare genetic illnesses are frequently challenging to identify, which can have serious repercussions. In light of the recent sequencing of the entire human genome, genetic screening is being proposed as a key possibility for translating genetic and genomic advances into improvements in population health. Clinical applications of whole-sequencing genetics have already shown a reduction in diagnostic odyssey in both adults and children as well as an improvement in the length of stay in intensive care units for critically ill children. This study delves deeper into the rare condition that has been mentioned and its catastrophic impact on children. . Strong efforts are being made to prevent the disease occurrence among children.
Introduction
Gene alterations are the root cause of genetic illness disorders. A family may have more than one member with an inherited ailment. The affected person may experience some others for the first time. Rare genetic disorders are frequently complex and dangerous. They might advance, meaning that as kid’s age, they might get worse. A rare genetic disorder might be difficult to diagnose, and this can have significant consequences. It can diminish the chance for individualized treatment, delay access to resources and supports, delay access to early therapies that could help manage symptoms, and affect planning for additional children.
1.2 Methodology
There are many, diverse, and geographically dispersed rare diseases (RDs). Most are chronic, many are avoidable or treatable, and many cause early death. Despite their uniqueness, RDs have similarities due to their rarity, which calls for an all-encompassing public health strategy1. In a study, among those who reported their age at onset (n = 5018), 81.3% (or 3510 people) were primarily pediatric, 908 (18.2%) were both pediatric and adult, and 600 (11.9%) were entirely
Adult. 71.9 percent of RDs—4440—are categorized as genetic. 79.7% of the genetic RDs had one (72.4%) or more (7.3%) inheritance patterns annotated.
Fig 1 Distribution of genetic uncommon disease inheritance patterns3.
This study dives deeper into few rare genetic diseases found in children.
2.1 Epidermolysis Bullosa
With an estimated 500 000 instances worldwide, epidermolysis bullosa (EB) refers to a category of uncommon, clinically and genetically diverse genodermatoses. Mechanobullous dermatoses are characterised by moderate to extreme fragility of epithelial tissues with prototypical blistering or erosions after little stress. At least 20 genes involved in cytoskeletal keratin intermediate filaments, cell junctions like desmosomes and hemidesmosomes, and other molecules involved in intraepidermal adhesion and dermo-epidermal anchorage of skin and mucous membranes are all mutated in epidermolysis bullosa4. Several genes have undergone mutations that cause EB; some of these mutations are autosomal dominant, while others are autosomal recessive. A problem with skin's epidermis and dermis attaching to or within one another is the underlying mechanism. There are four primary types: Kindler syndrome, junctional epidermolysis bullosa, dystrophic epidermolysis bullosa, and epidermolysis bullosa simplex. Skin biopsy and conclusive genetic testing are used to confirm the diagnosis, which was initially hypothesised based on symptoms. From moderate to severe, EB can range in severity. In various EB forms and subtypes, the eye, ear, nose, upper airway, gastrointestinal, and genitourinary tracts may have severe problems. The illness currently has no known cure.
Fig 2 Dominant dystrophic epidermolysis bullosa - 12.12 per 1 million live
Births. Recessive dystrophic epidermolysis bullosa - 3.05 per 1 million
live births
2.2 Pierre Robin Sequence
Pierre Robin sequence occurs in 1/8500 to 1/14,000 births. This phenotype has a number of underlying reasons and may appear alone or in tandem with a syndromic appearance. A high prevalence of twins with PRS provides support for a genetic aetiology. Additionally, there is a greater prevalence of cleft lip and palate among close relatives of infants with PRS.Deletions on 2q and 4p, as well as duplications on 3p, 3q, 7q, 78q, 10 p, 14q, 16p, and 22q, are linked to cleft palate. Deletions in 4p, 4q, 6q, and 11q, as well as duplications on 10q and 18q, are linked to micrognathia.
Fig 3 Percentage by specialisation of new Pierre Robin
newborns seen on average each year7.
2.3 Ataxia
It is important to look into the underlying aetiology of ataxia, which is defined as decreased coordination of voluntary muscle action. Ataxia is a physical finding, not a disease. Ataxia may be one of the presenting symptoms or the patient's main complaint. Ataxia is typically brought on by poor vestibular or proprioceptive afferent input to the cerebellum or by cerebellar pathology. Spinocerebellar ataxias [SCAs] of genetic origin, for example, can have an insidious onset and a chronic, slowly progressing clinical course. Ataxias can also have an acute onset, particularly those caused by cerebellar infarction, haemorrhage, or infection, which can progress rapidly and have disastrous consequences. Ataxia can also develop subacutely as a result of immune or viral diseases, with potentially narrow treatment windows.
Ataxia is a condition that affects the cerebellum and its afferent and efferent connections, the vestibular system, and the proprioceptive sensory pathway (Figure 4). The cerebellum is often divided into the cerebellar hemispheres and the midline cerebellum. A separate form of ataxia may manifest as a result of lesions in each of these areas.
Fig 4 Neuroanatomical and Clinical Ataxia Feature Correlation.
3.1 Future overview
The future of genetic diseases seems to end soon. The new application has been proven as a huge success for the fall of genetic diseases. Genetic screening is being suggested as a key possibility for converting genetic and genomic breakthroughs into improvements in population health in light of the recent sequencing of the full human genome. Genetics has already begun to change as a result of next-generation sequencing (NGS), and clinical applications of whole-sequencing genetics have already demonstrated a reduction in diagnostic odyssey in both adults and children as well as a reduction in the length of stay in intensive care units for critically ill children. Interest in using molecular testing for NBS is rising as costs are coming down and new genotyping and sequencing technological platforms are being developed. There is considerable interest in incorporating more DNA testing methods into NBS because to the ability to perform DNA testing on filter paper and the declining prices of DNA testing, which would significantly improve the ability to discover rare but fatal illnesses.
4.1 Conclusion
The genetic illness among children have always been in high ratios. The rare kinds of genetic diseases had a sudden growth among the young people. The diseases rate continues to rise due to greater chances of mutation occurrence. The rare kind of disease discussed and their disastrous effect on children has been discussed. The research of the diseases, Epidermolysis Bullosa, Pierre Robin Sequence and Ataxia, have advanced considerably. The treatment for them is under process. The new genetic development have caused a fall to the occurrence of disease. Strong efforts are being made to prevent the disease occurrence among children.
Bibliography
Valdez, R., Ouyang, L., & Bolen, J. (2016). Public health and rare diseases: oxymoron no more. Preventing chronic disease, 13.
Nguengang Wakap, S., Lambert, D. M., Olry, A., Rodwell, C., Gueydan, C., Lanneau, V., Murphy, D., Le Cam, Y., & Rath, A. (2020). Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database. European Journal of Human Genetics, 28(2), 165-173. https://doi.org/10.1038/s41431-019-0508-0
Nguengang Wakap, S., Lambert, D. M., Olry, A., Rodwell, C., Gueydan, C., Lanneau, V., Murphy, D., Le Cam, Y., & Rath, A. (2020). Estimating cumulative point prevalence of rare diseases: Analysis of the Orphanet database. European Journal of Human Genetics, 28(2), 165-173. https://doi.org/10.1038/s41431-019-0508-0
Prodinger, C., Reichelt, J., Bauer, J. W., & Laimer, M. (2019). Epidermolysis bullosa: Advances in research and treatment. Experimental Dermatology, 28(10), 1176-1189. https://doi.org/10.1111/exd.13979
Hon, K. L., Chu, S., & Leung, A. K. C. (2022). Epidermolysis Bullosa: Pediatric Perspectives. Current pediatric reviews, 18(3), 182–190. https://doi.org/10.2174/1573396317666210525161252
Gangopadhyay, N., Mendonca, D. A., & Woo, A. S. (2012). Pierre Robin Sequence. Seminars in Plastic Surgery, 26(2), 76-82. https://doi.org/10.1055/s-0032-1320065
Collins, B., Powitzky, R., Robledo, C., Rose, C., & Glade, R. (2014, May). Airway Management in Pierre Robin Sequence: Patterns of Practice. The Cleft Palate-Craniofacial Journal, 51(3), 283–289. https://doi.org/10.1597/12-214
Ashizawa, T., & Xia, G. (2016). Ataxia. Continuum : Lifelong Learning in Neurology, 22(4 Movement Disorders), 1208-1226. https://doi.org/10.1212/CON.0000000000000362
Ashizawa, T., & Xia, G. (2016). Ataxia. Continuum : Lifelong Learning in Neurology, 22(4 Movement Disorders), 1208-1226. https://doi.org/10.1212/CON.0000000000000362
Bouvier, D., & Giguère, Y. (2019, July 1). Newborn Screening for Genetic Diseases: An Overview of Current and Future Applications. OBM Genetics, 3(3), 1–1. https://doi.org/10.21926/obm.genet.1903093
Comments