Branding of subjects affected with genetic syndromes of severe short stature in developing countries

Guevara‐Aguirre, Jaime; Guevara, Carolina; Guevara, Alexandra; Gavilanes, Antonio W. D.

doi:10.1136/bcr-2019-231737

Cited by 7 publications

(9 citation statements)

References 62 publications

(81 reference statements)

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“…The flow chart of the selected patients is shown in Figure 2 A. Only the KBGS patients with ANKRD11 gene variation were included ( n = 253) [ 2 , 5 , 8 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. The types of variations included frameshift variation ( n = 158), nonsense variation ( n = 61), copy number variation ( n = 13), missense variation ( n = 13), splice site variation ( n = 6), and deletion variation ( n = 2).…”

Section: Resultsmentioning

confidence: 99%

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature

Gao

Zhao

Cao

et al. 2022

JPM

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KBG syndrome (KBGS) is a rare autosomal dominant inherited disease that involves multiple systems and is associated with variations in the ankyrin repeat domain 11 (ANKRD11) gene. We report the clinical and genetic data for 13 Chinese KBGS patients diagnosed by genetic testing and retrospectively analyse the genotypes and phenotypes of previously reported KBGS patients. The 13 patients in this study had heterozygous variations in the ANKRD11 gene, including seven frameshift variations, three nonsense variations, and three missense variations. They carried 11 variation sites, of which eight were previously unreported. The clinical phenotype analysis of these 13 patients and 240 previously reported patients showed that the occurrence rates of craniofacial anomalies, dental anomalies, global developmental delays, intellectual disability/learning difficulties, limb anomalies, and behavioural anomalies were >70%. The occurrence rates of short stature, delayed bone age, and spinal vertebral body anomalies were >50%. The frequency of global developmental delays and intellectual disability/learning difficulties in patients with truncated ANKRD11 gene variation was higher than that in patients with missense variation in the ANKRD11 gene (p < 0.05). Collectively, this study reported the genotypic and phenotypic characteristics of the largest sample of KBGS patients from China and discovered eight new ANKRD11 gene variations, which enriched the variation spectrum of the ANKRD11 gene. Variation in the ANKRD11 gene mainly caused craniofacial anomalies, growth and developmental anomalies, skeletal system anomalies, and nervous system anomalies. Truncated variation in the ANKRD11 gene is more likely to lead to global growth retardation and intellectual disability/learning difficulties than missense variation in ANKRD11.

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Section: Resultsmentioning

confidence: 99%

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature

Gao

Zhao

Cao

et al. 2022

JPM

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“…As such, access to genetic testing to support SPIGFD diagnosis is limited in many regions; particularly for patients in developing countries and from lower-income backgrounds, genetic testing may not be an option. Countries with particularly poor access to genetic testing often rely on outsourcing to overseas laboratories, prolonging the time to diagnosis for patients in these regions [ 46 ]. Establishing partnerships between healthcare centers and genetic laboratories, and encouraging increased collaboration between centers with genetic testing resources and smaller centers with limited experience in SPIGFD, would provide an opportunity to improve diagnosis for patients.…”

Section: Diagnosismentioning

confidence: 99%

“…Yet for other regions, including most of South America, the Middle East and Africa, people with SPIGFD are unable to access rhIGF-1 locally due to a lack of approval. Poor infrastructure, political unrest, economic challenges, or other barriers to patient safety follow-up can further hinder access for these patients, and lead managed access programs that do exist in these areas to be withdrawn or suspended unexpectedly [ 46 ]. Such challenges are relevant to countries in the Middle East, where SPIGFD cohorts have been well-characterized but many patients are from low socio-economic backgrounds [ 46 ].…”

Section: Access To Treatmentmentioning

confidence: 99%

Challenges in the care of individuals with severe primary insulin-like growth factor-I deficiency (SPIGFD): an international, multi-stakeholder perspective

Backeljauw,

Andrews,

Bang

et al. 2023

Orphanet J Rare Dis

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Background Severe primary insulin-like growth factor-I (IGF-I) deficiency (SPIGFD) is a rare growth disorder characterized by short stature (standard deviation score [SDS] ≤ 3.0), low circulating concentrations of IGF-I (SDS ≤ 3.0), and normal or elevated concentrations of growth hormone (GH). Laron syndrome is the best characterized form of SPIGFD, caused by a defect in the GH receptor (GHR) gene. However, awareness of SPIGFD remains low, and individuals living with SPIGFD continue to face challenges associated with diagnosis, treatment and care. Objective To gather perspectives on the key challenges for individuals and families living with SPIGFD through a multi-stakeholder approach. By highlighting critical gaps in the awareness, diagnosis, and management of SPIGFD, this report aims to provide recommendations to improve care for people affected by SPIGFD globally. Methods An international group of clinical experts, researchers, and patient and caregiver representatives from the SPIGFD community participated in a virtual, half-day meeting to discuss key unmet needs and opportunities to improve the care of people living with SPIGFD. Results As a rare disorder, limited awareness and understanding of SPIGFD amongst healthcare professionals (HCPs) poses significant challenges in the diagnosis and treatment of those affected. Patients often face difficulties associated with receiving a formal diagnosis, delayed treatment initiation and limited access to appropriate therapy. This has a considerable impact on the physical health and quality of life for patients, highlighting a need for more education and clearer guidance for HCPs. Support from patient advocacy groups is valuable in helping patients and their families to find appropriate care. However, there remains a need to better understand the burden that SPIGFD has on individuals beyond height, including the impact on physical, emotional, and social wellbeing. Conclusions To address the challenges faced by individuals and families affected by SPIGFD, greater awareness of SPIGFD is needed within the healthcare community, and a consensus on best practice in the care of individuals affected by this condition. Continued efforts are also needed at a global level to challenge existing perceptions around SPIGFD, and identify solutions that promote equitable access to appropriate care. Medical writing support was industry-sponsored.

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“…Additionally, there have been many descriptions of subjects with severe growth impairment ( 8 ). Adelson relates the story of the sexual ateliotic dwarf (old term describing one not yet achieving perfection; in addition the term “dwarf” is now considered pejorative by some ( 9 ) and we shall use “little person”). Better known as General Tom Thumb, Charles Sherwood Stratton was born in Connecticut in 1838.…”

Section: Under-growthmentioning

confidence: 99%

Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future

2021

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Since antiquity Man has been fascinated by the variations in human (and animal) growth. Stories and art abound about giants and little people. Modern genetics have solved some of etiologies at both extremes of growth. Serious study began with the pathophysiology of acromegaly followed by early attempts at treatment culminating in modern endoscopic surgery and multiple pharmacologic agents. Virtually at the same time experiments with the removal of the pituitary from laboratory animals noted the slowing or stopping of linear growth and then over a few decades the extraction and purification of a protein within the anterior pituitary that restored, partially or in full, the animal’s growth. Human growth hormone was purified decades after those from large animals and it was noted that it was species specific, that is, only primate growth hormone was metabolically active in primates. That was quite unlike the beef and pork insulins which revolutionized the care of children with diabetes mellitus. A number of studies included mild enzymatic digestion of beef growth hormone to determine if those “cores” had biologic activity in primates and man. Tantalizing data showed minimal but variable metabolic efficacy leading to the “active core” hypothesis, for these smaller peptides would be amenable to peptide synthesis in the time before recombinant DNA. Recombinant DNA changed the landscape remarkably promising nearly unlimited quantities of metabolically active hormone. Eight indications for therapeutic use have been approved by the Food and Drug Administration and a large number of clinical trials have been undertaken in multiple other conditions for which short stature in childhood is a sign. The future predicts other clinical indications for growth hormone therapy (and perhaps other components of the GH?IGF-1 axis), longer-acting analogues and perhaps a more physiologic method of administration as virtually all methods at present are far from physiologic.

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Branding of subjects affected with genetic syndromes of severe short stature in developing countries

Cited by 7 publications

References 62 publications

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature

Genetic and Phenotypic Spectrum of KBG Syndrome: A Report of 13 New Chinese Cases and a Review of the Literature

Challenges in the care of individuals with severe primary insulin-like growth factor-I deficiency (SPIGFD): an international, multi-stakeholder perspective

Human Growth and Growth Hormone: From Antiquity to the Recominant Age to the Future

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