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Maternal & Child Nutrition May 2016Childhood stunting is the best overall indicator of children's well-being and an accurate reflection of social inequalities. Stunting is the most prevalent form of child... (Review)
Review
Childhood stunting is the best overall indicator of children's well-being and an accurate reflection of social inequalities. Stunting is the most prevalent form of child malnutrition with an estimated 161 million children worldwide in 2013 falling below -2 SD from the length-for-age/height-for-age World Health Organization Child Growth Standards median. Many more millions suffer from some degree of growth faltering as the entire length-for-age/height-for-age z-score distribution is shifted to the left indicating that all children, and not only those falling below a specific cutoff, are affected. Despite global consensus on how to define and measure it, stunting often goes unrecognized in communities where short stature is the norm as linear growth is not routinely assessed in primary health care settings and it is difficult to visually recognize it. Growth faltering often begins in utero and continues for at least the first 2 years of post-natal life. Linear growth failure serves as a marker of multiple pathological disorders associated with increased morbidity and mortality, loss of physical growth potential, reduced neurodevelopmental and cognitive function and an elevated risk of chronic disease in adulthood. The severe irreversible physical and neurocognitive damage that accompanies stunted growth poses a major threat to human development. Increased awareness of stunting's magnitude and devastating consequences has resulted in its being identified as a major global health priority and the focus of international attention at the highest levels with global targets set for 2025 and beyond. The challenge is to prevent linear growth failure while keeping child overweight and obesity at bay.
Topics: Body Height; Child, Preschool; Cognition Disorders; Growth Disorders; Humans; Infant; Infant, Newborn; Neurodevelopmental Disorders; Reference Values; Risk Factors; World Health Organization
PubMed: 27187907
DOI: 10.1111/mcn.12231 -
Hormone Research in Paediatrics 2019The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international... (Review)
Review
The Growth Hormone Research Society (GRS) convened a Workshop in March 2019 to evaluate the diagnosis and therapy of short stature in children. Forty-six international experts participated at the invitation of GRS including clinicians, basic scientists, and representatives from regulatory agencies and the pharmaceutical industry. Following plenary presentations addressing the current diagnosis and therapy of short stature in children, breakout groups discussed questions produced in advance by the planning committee and reconvened to share the group reports. A writing team assembled one document that was subsequently discussed and revised by participants. Participants from regulatory agencies and pharmaceutical companies were not part of the writing process. Short stature is the most common reason for referral to the pediatric endocrinologist. History, physical examination, and auxology remain the most important methods for understanding the reasons for the short stature. While some long-standing topics of controversy continue to generate debate, including in whom, and how, to perform and interpret growth hormone stimulation tests, new research areas are changing the clinical landscape, such as the genetics of short stature, selection of patients for genetic testing, and interpretation of genetic tests in the clinical setting. What dose of growth hormone to start, how to adjust the dose, and how to identify and manage a suboptimal response are still topics to debate. Additional areas that are expected to transform the growth field include the development of long-acting growth hormone preparations and other new therapeutics and diagnostics that may increase adult height or aid in the diagnosis of growth hormone deficiency.
Topics: Child; Growth Disorders; Human Growth Hormone; Humans
PubMed: 31514194
DOI: 10.1159/000502231 -
Nature Reviews. Nephrology Sep 2019Achieving normal growth is one of the most challenging problems in the management of children with chronic kidney disease (CKD). Treatment with recombinant human growth... (Review)
Review
Achieving normal growth is one of the most challenging problems in the management of children with chronic kidney disease (CKD). Treatment with recombinant human growth hormone (GH) promotes longitudinal growth and likely enables children with CKD and short stature to reach normal adult height. Here, members of the European Society for Paediatric Nephrology (ESPN) CKD-Mineral and Bone Disorder (MBD), Dialysis and Transplantation working groups present clinical practice recommendations for the use of GH in children with CKD on dialysis and after renal transplantation. These recommendations have been developed with input from an external advisory group of paediatric endocrinologists, paediatric nephrologists and patient representatives. We recommend that children with stage 3-5 CKD or on dialysis should be candidates for GH therapy if they have persistent growth failure, defined as a height below the third percentile for age and sex and a height velocity below the twenty-fifth percentile, once other potentially treatable risk factors for growth failure have been adequately addressed and provided the child has growth potential. In children who have received a kidney transplant and fulfil the above growth criteria, we recommend initiation of GH therapy 1 year after transplantation if spontaneous catch-up growth does not occur and steroid-free immunosuppression is not a feasible option. GH should be given at dosages of 0.045-0.05 mg/kg per day by daily subcutaneous injections until the patient has reached their final height or until renal transplantation. In addition to providing treatment recommendations, a cost-effectiveness analysis is provided that might help guide decision-making.
Topics: Child; Child, Preschool; Growth Disorders; Human Growth Hormone; Humans; Kidney Transplantation; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 31197263
DOI: 10.1038/s41581-019-0161-4 -
Italian Journal of Pediatrics Mar 2022Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first... (Review)
Review
BACKGROUND
Constitutional delay of growth and puberty (CDGP) is classified as the most frequent cause of delayed puberty (DP). Finding out the etiology of DP during first evaluation may be a challenge. In details, pediatricians often cannot differentiate CDGP from permanent hypogonadotropic hypogonadism (PHH), with definitive diagnosis of PHH awaiting lack of puberty by age 18 yr. Neverthless, the ability in providing a precise and tempestive diagnosis has important clinical consequences.
MAIN TEXT
A growth failure in adolescents with CDGP may occur until the onset of puberty; after that the growth rate increases with rapidity. Bone age is typically delayed. CDGP is generally a diagnosis of exclusion. Nevertheless, other causes of DP must be evaluated. A family history including timing of puberty in the mother and in the father as well as physical examination may givee information on the cause of DP. Patients with transient delay in hypothalamic-pituitary-gonadal axis maturation due to associated conditions, such as celiac disease, inflammatory bowel diseases, kidney insufficiency and anorexia nervosa, may experience a functional hypogonadotropic hypogonadism. PHH revealing testosterone or estradiol low serum values and reduced FSH and LH levels may be connected to abnormalities in the central nervous system. So, magnetic resonance imaging is required in order to exclude either morphological alterations or neoplasia. If the adolescent with CDGP meets psychological difficulties, treatment is recommended.
CONCLUSION
Even if CDGP is considered a variant of normal growth rather than a disease, short stature and retarded sexual development may led to psychological problems, sometimes associated to a poor academic performance. A prompt and precise diagnosis has an important clinical outcome. Aim of this mini-review is throwing light on management of patients with CDGP, emphasizing the adolescent diagnosis and trying to answer all questions from paediatricians.
Topics: Adolescent; Female; Growth Disorders; Humans; Hypogonadism; Klinefelter Syndrome; Puberty; Puberty, Delayed
PubMed: 35331309
DOI: 10.1186/s13052-022-01242-5 -
Current Opinion in Pediatrics Aug 2021Short stature is a common clinical manifestation in children. Yet, a cause is often unidentifiable in the majority of children with short stature by a routine screening... (Review)
Review
PURPOSE OF REVIEW
Short stature is a common clinical manifestation in children. Yet, a cause is often unidentifiable in the majority of children with short stature by a routine screening approach. The purpose of this review is to describe the optimal genetic approach for evaluating short stature, challenges of genetic testing, and recent advances in genetic testing for short stature.
RECENT FINDINGS
Genetic testing, such as karyotype, chromosomal microarray, targeted gene sequencing, or exome sequencing, has served to identify the underlying genetic causes of short stature. When determining which short stature patient would benefit from genetic evaluation, it is important to consider whether the patient would have a single identifiable genetic cause. Specific diagnoses permit clinicians to predict responses to growth hormone treatment, to understand the phenotypic spectrum, and to understand any associated co-morbidities.
SUMMARY
The continued progress in the field of genetics and enhanced capabilities provided by genetic testing methods expands the ability of physicians to evaluate children with short stature for underlying genetic defects. Continued effort is needed to elaborate new genetic causes of linear growth disorders, therefore, we expand the list of known genes for short stature, which will subsequently increase the rate of genetic diagnosis for children with short stature.
Topics: Body Height; Child; Dwarfism; Genetic Testing; Growth Disorders; Humans; Exome Sequencing
PubMed: 34101704
DOI: 10.1097/MOP.0000000000001033 -
Current Opinion in Pediatrics Aug 2018Genome-wide approaches including genome-wide association studies as well as exome and genome sequencing represent powerful new approaches that have improved our ability... (Review)
Review
PURPOSE OF REVIEW
Genome-wide approaches including genome-wide association studies as well as exome and genome sequencing represent powerful new approaches that have improved our ability to identify genetic causes of human disorders. The purpose of this review is to describe recent advances in the genetic causes of short stature.
RECENT FINDINGS
In addition to SHOX deficiency which is one of the most common causes of isolated short stature, PAPPA2, ACAN, NPPC, NPR2, PTPN11 (and other rasopathies), FBN1, IHH and BMP2 have been identified in isolated growth disorders with or without other mild skeletal findings. In addition, novel genetic causes of syndromic short stature have been discovered, including pathogenic variants in BRCA1, DONSON, AMMECR1, NFIX, SLC25A24, and FN1.
SUMMARY
Isolated growth disorders are often monogenic. Specific genetic causes typically have specific biochemical and/or phenotype characteristics which are diagnostically helpful. Identification of additional subjects with a specific genetic cause of short stature often leads to a broadening of the known clinical spectrum for that condition. The identification of novel genetic causes of short stature has provided important insights into the underlying molecular mechanisms of growth failure.
Topics: Child; Dwarfism; Genetic Markers; Genetic Predisposition to Disease; Genetic Testing; Genome-Wide Association Study; Growth Disorders; Humans; Exome Sequencing; Whole Genome Sequencing
PubMed: 29787394
DOI: 10.1097/MOP.0000000000000653 -
Ethiopian Journal of Health Sciences May 2022Stunting occurs due to chronic malnutrition and is a major problem for children in developing countries. It is important to evaluate the impact of stunting on the...
BACKGROUND
Stunting occurs due to chronic malnutrition and is a major problem for children in developing countries. It is important to evaluate the impact of stunting on the development of children. This study aimed to investigate the impact of stunting on the development of children between 1-3 years of age.
METHODS
This cross-sectional study was conducted from July 2020 to March 2021 in Surabaya, Indonesia. A questionnaire and growth assessment were done, following the development measurement to stunted and non-stunted children who met the inclusion and exclusion criteria. Development was measured by the Denver Developmental Screening Test II (DDST-II), and Cognitive Adaptive Test/Clinical Linguistic & Auditory Milestone (CAT/CLAMS) scales.
RESULTS
Three hundred children are included in this study, consisting of 150 stunted and 150 non-stunted children. Stunted children had a higher risk to be suspected of delayed development compared to non-stunted children. The Crude Odd Ratio was 2.98, 4.24, 4.75 with the p-value 0.006, 0.001. and 0.001 respectively. The Adjusted Odd Ratio was 0.34, 0.24, 0.21 with p-value of 0.008, 0.001, and 0.001 respectively.
CONCLUSION
Stunting is associated with suspected development delay among children 1-3 years of age. Initiatives related to prevention need to be established and nutrition advice needs to be provided.
Topics: Cross-Sectional Studies; Growth Disorders; Humans; Indonesia; Infant; Nutritional Status; Odds Ratio; Prevalence
PubMed: 35813667
DOI: 10.4314/ejhs.v32i3.13 -
TheScientificWorldJournal 2021OSA pediatric subjects suffer from episodes of upper airway obstruction that can be partial or complete, with atypical sleep patterns and blood-gas level alteration. If... (Review)
Review
OSA pediatric subjects suffer from episodes of upper airway obstruction that can be partial or complete, with atypical sleep patterns and blood-gas level alteration. If poor treated and/or diagnosed, it can cause cardiovascular disease, learning difficulties, behavioural issues, and retardation of growth. In the literature, there are conflicting evidence about OSA assessment and treatment in pediatric age, so the aim of this paper is to highlight the multidisciplinary approach in the management of sleep disorders, stressing the role of the pediatric dentist in both diagnosing and treating the OSAS in children, according to the current evidence of the treatment options effectiveness of the syndrome itself. . Scientific evidence shows that OSAS management requires a multidisciplinary approach in order to make an early diagnosis and a correct treatment plan. The orthodontic treatment approach includes orthopedic maxillary expansion and mandibular advancement using intraoral appliances. Hence, the orthodontist and the pediatric dentist play an important role not only in early diagnosis but also in the treatment of pediatric OSAS.
Topics: Airway Obstruction; Cardiovascular Diseases; Child; Dentists; Early Diagnosis; Growth Disorders; Humans; Mandibular Advancement; Orthodontics, Corrective; Orthodontists; Sleep Apnea, Obstructive
PubMed: 33981185
DOI: 10.1155/2021/5591251 -
American Journal of Human Genetics Feb 2020Germline pathogenic variants in chromatin-modifying enzymes are a common cause of pediatric developmental disorders. These enzymes catalyze reactions that regulate...
Germline pathogenic variants in chromatin-modifying enzymes are a common cause of pediatric developmental disorders. These enzymes catalyze reactions that regulate epigenetic inheritance via histone post-translational modifications and DNA methylation. Cytosine methylation (5-methylcytosine [5mC]) of DNA is the quintessential epigenetic mark, yet no human Mendelian disorder of DNA demethylation has yet been delineated. Here, we describe in detail a Mendelian disorder caused by the disruption of DNA demethylation. TET3 is a methylcytosine dioxygenase that initiates DNA demethylation during early zygote formation, embryogenesis, and neuronal differentiation and is intolerant to haploinsufficiency in mice and humans. We identify and characterize 11 cases of human TET3 deficiency in eight families with the common phenotypic features of intellectual disability and/or global developmental delay; hypotonia; autistic traits; movement disorders; growth abnormalities; and facial dysmorphism. Mono-allelic frameshift and nonsense variants in TET3 occur throughout the coding region. Mono-allelic and bi-allelic missense variants localize to conserved residues; all but one such variant occur within the catalytic domain, and most display hypomorphic function in an assay of catalytic activity. TET3 deficiency and other Mendelian disorders of the epigenetic machinery show substantial phenotypic overlap, including features of intellectual disability and abnormal growth, underscoring shared disease mechanisms.
Topics: Adult; Amino Acid Sequence; Autistic Disorder; Child; Child, Preschool; DNA Demethylation; Developmental Disabilities; Dioxygenases; Embryonic Development; Female; Gene Expression Regulation, Developmental; Growth Disorders; Humans; Infant; Male; Middle Aged; Movement Disorders; Pedigree; Protein Conformation; Sequence Homology; Young Adult
PubMed: 31928709
DOI: 10.1016/j.ajhg.2019.12.007 -
Clinical Genetics Jan 2022Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These... (Review)
Review
Growth promoting variants in PIK3CA cause a spectrum of developmental disorders, depending on the developmental timing of the mutation and tissues involved. These phenotypically heterogeneous entities have been grouped as PIK3CA-Related Overgrowth Spectrum disorders (PROS). Deep sequencing technologies have facilitated detection of low-level mosaic, often necessitating testing of tissues other than blood. Since clinical management practices vary considerably among healthcare professionals and services across different countries, a consensus on management guidelines is needed. Clinical heterogeneity within this spectrum leads to challenges in establishing management recommendations, which must be based on patient-specific considerations. Moreover, as most of these conditions are rare, affected families may lack access to the medical expertise that is needed to help address the multi-system and often complex medical issues seen with PROS. In March 2019, macrocephaly-capillary malformation (M-CM) patient organizations hosted an expert meeting in Manchester, United Kingdom, to help address these challenges with regards to M-CM syndrome. We have expanded the scope of this project to cover PROS and developed this consensus statement on the preferred approach for managing affected individuals based on our current knowledge.
Topics: Class I Phosphatidylinositol 3-Kinases; Consensus Development Conferences as Topic; Diagnosis, Differential; Disease Management; Genetic Association Studies; Genetic Predisposition to Disease; Genetic Testing; Growth Disorders; Humans; Phenotype; Prenatal Diagnosis; Standard of Care
PubMed: 34240408
DOI: 10.1111/cge.14027