RESUMEN

Children born small for gestational age (SGA) are defined as those having birth weight and/or length below -2 SD for gestational age. In approximately 90% of cases, SGA children experience catch-up growth in the first two years of life and a subsequent regular growth rate, reaching normal adult height. However, in the remaining 10% of cases, SGA children fail to have catch-up growth, showing persistent short stature and a constantly impaired growth rate, leading to decreased adult height compared with both general population and their mid-parental height. Therefore, in these children GH treatment may be indicated to improve growth outcome. As it can be started in most countries from the age of 4 years and is usually recommended until the completion of puberty, long-term GH treatment in SGA children (namely, longer than three years) showed a persistent improvement in height and an initial improvement in growth rate in the first year of treatment, followed by a stable, regular growth rate over time. In the present article, we systematically reviewed the currently available reports about efficacy of long-term GH treatment in SGA children, with a particular focus on growth rate over time and adult height.

RESUMEN

Ankyrin repeat domain containing-protein 11 (ANKRD11), a transcriptional factor predominantly localized in the cell nucleus, plays a crucial role in the expression regulation of key genes by recruiting chromatin remodelers and interacting with specific transcriptional repressors or activators during numerous biological processes. Its pathogenic variants are strongly linked to the pathogenesis and progression of multisystem disorder known as KBG syndrome. With the widespread application of high-throughput DNA sequencing technologies in clinical medicine, numerous pathogenic variants in the ANKRD11 gene have been reported. Patients with KBG syndrome usually exhibit a broad phenotypic spectrum with a variable degree of severity, even if having identical variants. In addition to distinctive dental, craniofacial and neurodevelopmental abnormalities, patients often present with skeletal anomalies, particularly postnatal short stature. The relationship between ANKRD11 variants and short stature is not well-understood, with limited knowledge regarding its occurrence rate or underlying biological mechanism involved. This review aims to provide an updated analysis of the molecular spectrum associated with ANKRD11 variants, investigate the prevalence of the short stature among patients harboring these variants, evaluate the efficacy of recombinant human growth hormone in treating children with short stature and ANKRD11 variants, and explore the biological mechanisms underlying short stature from both scientific and clinical perspectives. Our investigation indicated that frameshift and nonsense were the most frequent types in 583 pathogenic or likely pathogenic variants identified in the ANKRD11 gene. Among the 245 KBGS patients with height data, approximately 50% displayed short stature. Most patients showed a positive response to rhGH therapy, although the number of patients receiving treatment was limited. ANKRD11 deficiency potentially disrupts longitudinal bone growth by affecting the orderly differentiation of growth plate chondrocytes. Our review offers crucial insights into the association between ANKRD11 variants and short stature and provides valuable guidance for precise clinical diagnosis and treatment of patients with KBG syndrome.

Asunto(s)

Fenotipo , Proteínas Represoras , Humanos , Proteínas Represoras/genética , Anomalías Múltiples/genética , Discapacidad Intelectual/genética , Anomalías Dentarias/genética , Anomalías Dentarias/patología , Craneosinostosis/genética , Craneosinostosis/patología , Deleción Cromosómica , Enfermedades del Desarrollo Óseo , Facies

RESUMEN

CONTEXT: Long-term data regarding HRQoL and problem behaviour in adults born SGA who were treated with GH during childhood are lacking. OBJECTIVE: To investigate longitudinal changes in HRQoL and problem behaviour in adults born SGA during 12 years after cessation of childhood GH-treatment (SGA-GH), and compare these with 3 control groups at age around 30 years. PARTICIPANTS: 176 SGA-GH adults and 3 untreated age-matched control groups: 50 born SGA with short stature (SGA-S), 77 born SGA with spontaneous catch-up growth to normal height (SGA-CU) and 99 born appropriate-for-gestational-age with normal height (AGA). MAIN OUTCOME MEASURES: HRQoL and problem behavior were assessed using TNO-AZL Adults Quality of Life questionnaire (TAAQoL) and Adolescent Behavior Check List (ABCL) at 6 months, 2, 5 and 12 years after GH-cessation. Data at 12-years after GH-cessation were compared with 3 control groups. RESULTS: During 12 years after GH-cessation, HRQoL remained similar on 9 subscales in SGA-GH adults, but decreased on 3 subscales (gross motor functioning, pain, sleep). Externalizing problem behaviour decreased significantly and internalizing problem behaviour tended to decrease. SGA-GH and SGA-S adults had similar HRQoL and problem behaviour. SGA-GH adults had, compared to AGA adults, similar HRQoL on 7 subscales, lower HRQoL on 5 subscales and more internalizing and externalizing problem behaviour. All SGA adults had lower HRQoL and more internalizing problem behaviour than AGA adults. Adult height associated negatively with externalizing problem behaviour, but the influence was small. CONCLUSIONS: During 12 years after GH-cessation, HRQoL remained mostly similar and problem behaviour decreased in SGA-GH adults. SGA-GH and SGA-S adults had similar HRQoL and problem behaviour. All SGA adults had lower HRQoL and more internalizing problem behaviour than AGA adults.

RESUMEN

Background: Short stature is one of the most prevalent endocrine disorders in children, and its genetic basis is a complex and actively researched subject. Currently, there is limited genetic research on exome sequencing for short stature, and more large-scale studies are necessary for further exploration. Methods: The retrospective study entailed investigation of 98 Chinese children with short statures (height SDS ≤ -2.5) of unknown etiologies recruited between 2017 and 2021. Whole-exome sequencing (WES) was performed on these patients to identify the potential genetic etiologies. The clinical data were reviewed retrospectively to assess the pathogenicity of the identified mutations. Additionally, 31 patients consented to and received recombinant human growth hormone (rhGH) therapy for 12 months. The short-term effects of rhGH treatment were evaluated across different etiologies of patients with short statures. Results: The WES results were used to identify 31 different variants in 18 genes among 24 (24.5%) patients. Individuals with more severe short statures were more likely to have underlying genetic etiologies. Short stature accompanied by other phenotypes had significantly higher diagnostic yields than simple severe short stature. The rhGH therapy demonstrated efficacy in most children. Nevertheless, the treatment response was suboptimal in a boy diagnosed with 3M syndrome. Conclusion: WES is an important approach for confirming genetic disorders in patients with severe short statures of unknown etiologies, suggesting that it could be used as a primary diagnostic strategy. The administration of rhGH may not be suitable for all children with short statures, and the identification of the genetic cause of short stature by WES has significant guidance value for rhGH treatment.

RESUMEN

Background: Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. Yet, previous studies lacked an appropriate control group which is a major limitation. We prospectively studied cerebral white matter hyperintensities (WMHs) in adults born SGA at 12 years after cessation of childhood GH-treatment (SGA-GH), compared to appropriate controls. Methods: In this prospective cohort study, performed between May 2016 and December 2020, total WMHs, periventricular WMHs (PVWMHs) and deep WMHs (DWMHs) were the primary outcomes of the study, they were qualitatively assessed using 3 Tesla (T) Magnetic Resonance Imaging (MRI) and scored using the Fazekas scale in SGA-GH adults and in 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). Regression analyses were performed in the total cohort to evaluate the associations of GH-treatment and birth characteristics with WMHs. Findings: 297 adults were investigated (91 SGA-GH, 206 controls). Prevalence of total WMHs was 53.8% (95% CI 43.1-64.3) in SGA-GH, 40.5% (95% CI 25.6-56.7) in SGA-S, 73.9% (95% CI 61.9-83.7) in SGA-CU and 41.1% (95% CI 31.1-51.6) in AGA adults. No statistically significant differences in total WMHs, PVWMHs and DWMHs were found between SGA-GH compared to SGA-S and AGA adults. Highest prevalence of all type of WMHs was found in SGA-CU adults compared to all groups. Higher prevalence of total WMHs was associated with lower birth weight standard deviation score (SDS), but not with GH-treatment. Interpretation: Our findings suggest that GH-treatment in children born SGA has no negative impact on the prevalence of all type of WMHs at 12 years after GH cessation compared to appropriate controls. SGA-CU adults had the highest prevalence of all type of WMHs around age 30 years. Funding: Novo Nordisk.

RESUMEN

OBJECTIVE: The aim of this study was to explore the impact of growth hormone (GH) therapy on the onset and progression of puberty in girls with idiopathic short stature. METHODS: This study included 541 girls aged between 4.5 and 10.6 years who were receiving GH treatment, monitored over a 22-year follow-up period. Of these, 126 girls have been followed up to the onset of menarche. The participants were divided into two groups: a ISS control group (n = 66) and a group receiving daily GH treatment at a dose of 0.15 iu/kg (n = 60). We assessed the pubertal development and GH usage of these girls every three months. RESULTS: (1) There was no significant difference in the onset of puberty between the growth hormone (GH) treatment group and the control group; however, the average duration of puberty was longer in the treatment group compared to the control group. (2) During puberty, there were no significant differences in height growth between the treated and untreated groups. (3) The duration of GH treatment showed a significant negative correlation with the age at onset of gonadal development and the age at menarche in females within the treatment group. CONCLUSION: GH treatment does not seem to accelerate the onset of puberty but may extend its duration, without significantly impacting height growth during puberty. Additionally, longer GH treatment duration is linked to earlier gonadal development and menarche in females.

Asunto(s)

Estatura , Trastornos del Crecimiento , Hormona de Crecimiento Humana , Menarquia , Pubertad , Humanos , Femenino , Niño , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/administración & dosificación , Pubertad/efectos de los fármacos , Trastornos del Crecimiento/tratamiento farmacológico , Menarquia/efectos de los fármacos , Estatura/efectos de los fármacos , Preescolar , Estudios de Seguimiento , Adolescente

RESUMEN

Background: Thailand has been administering the recombinant human growth hormone (rhGH) treatment for >20 years. Due to limited resources being available, efforts have been directed toward utilizing rhGH at the lowest feasible dose. However, there is currently a lack of evidence in terms of the efficacy and outcomes. Objective: To evaluate the auxological outcomes of growth hormone (GH) treatment and the GH secretion ability after reaching final adult height (FAH) and discontinuing rhGH. Methods: Data of 40 patients were retrospectively reviewed. The clinical characteristics, auxological data, and results of biochemical and endocrine investigations before and during rhGH treatment were evaluated. In addition, GH retesting was performed in 24 patients using the insulin tolerance test. Results: Twenty patients (50%) had complete growth hormone deficiency (GHD), defined as peak stimulated GH level <5 ng/mL, and the remaining patients had partial GHD. Most patients were male (n = 25, 62.5%). The mean age at which rhGH was initiated was 8.9 years. Patients with partial GHD received a higher dose of rhGH than those with complete GHD (30.9 µg/kg/d vs. 26.2 µg/kg/d, P = 0.02). Patients with complete and partial GHD reached FAH at height standard deviation scores (SDSs) of -0.65 and -1.47, respectively. The factors associated with obtaining a good clinical response in terms of height gain included peak-stimulated GH level, age of puberty, and age of discontinuing rhGH. After completing the rhGH treatment, 13 of the 24 patients showed normal GH secretion. Patients with multiple pituitary hormone deficiency (MPHD) were likely to have persistent GHD through adulthood (n = 8, 88.9%). Conclusion: This study has demonstrated that the use of low-dose rhGH could result in healthy populations achieving optimal FAHs. Patients with MPHD might not require retesting as they were likely to have persistent GHD. The results obtained in this research highlight the benefits of the treatment. This treatment can be applied in resource-limited countries.

RESUMEN

INTRODUCTION: Growth hormone (GH) treatment in children with growth hormone deficiency (GHD), short children born small for gestational age (SGA), and Turner syndrome (TS) is well established. However, a variety of parameters are still under discussion to achieve optimal growth results and efficiency of GH use in real-world treatment. METHODS: German GH-treatment naïve patients of the PATRO Children database were grouped according to their start of treatment into groups of 3 years from 2007 to 2018. Time trends in age, gender, GH dose, height standard deviation score (SDS), first-year growth response, and Index of Responsiveness (IoR) were investigated in children with GHD, short children born SGA, and TS starting GH treatment in the German patient population of the PATRO Children database from 2007 to 2018 to determine specific parameters for GH treatment optimization. RESULTS: All patient groups started GH treatment at a relatively high chronological age (2007-2009: GHD 8.33 ± 3.19, SGA 7.32 ± 2.52, TS 8.65 ± 4.39) with a slight but not significant trend towards younger therapy start up to 2016-2018 (GHD 8.04 ± 3.36, SGA 6.67 ± 2.65, TS 7.85 ± 3.38). In the GHD and SGA groups, female patients were underrepresented compared to male patients (GHD 32.3%, SGA 43.6%) with no significant change over the 4 time periods. Patients with GHD started GH treatment at a low dose (0.026 mg/kg/day). In SGA and TS patients, GH therapy was started below the registered dose recommendation (30.0 µg/kg/day and 33.7 µg/kg/day, respectively). In the first year of treatment, the mean GH dose was increased moderately (GHD: 30.7, SGA: 35.7, TS: 40.8 µg/kg/day). There was no significant change of GH dosing over time from 2007 to 2018. The IoR was comparable between time-groups for all 3 diagnoses. DISCUSSION: This study shows potential for improvement of GH treatment results in GHD, SGA, and TS patients in terms of early dose adjustment and younger age at the start of treatment. This is in accordance with important parameters used in prediction models.

RESUMEN

The ketogenic diet (KD) can have a negative impact on the linear growth and body composition of children. The aims of this study were to review two centers' experience with children who developed height deceleration on the KD and determine if the height deceleration was secondary to growth hormone deficiency (GHD), and if growth hormone therapy (GHT) would be effective and safe (not altering ketosis or seizure frequency). Retrospective chart reviews were performed on patients with KD referred to Endocrinology between 2013 and 2018. Seventeen children were identified. Data reviewed included: demographics, growth velocity, KD ratio, protein/calorie intake, lab results, GH dosage, Tanner stage, and seizure frequency, and endocrine recommendations. Descriptive statistics were performed. Of the 17 children referred to the Endocrine Division, seven children were growth hormone deficient and began GHT. Data were provided for six patients (2 males, 4 females; age 2-7 years at the start of KD) on the KD for >6 years and on GHT for >4 years. Growth for all patients stabilized or increased. IGF-1 z-scores normalized. GHT did not affect seizure frequency or ketosis. GHT in those with GHD can be an appropriate option allowing better growth while still maintaining ketogenic therapy and seizure control. PLAIN LANGUAGE SUMMARY: The KD can be an effective treatment for difficult-to-control epilepsy and some disorders of carbohydrate metabolism. The KD can adversely affect the linear growth (height) of children. This case series reviewed six patients who had slow linear growth. It was found that all six children had growth hormone deficiency, grew better with growth hormone treatments, and that their seizures and ketone levels were not affected.

Asunto(s)

Dieta Cetogénica , Hormona de Crecimiento Humana , Humanos , Femenino , Masculino , Niño , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/administración & dosificación , Hormona de Crecimiento Humana/uso terapéutico , Preescolar , Estudios Retrospectivos , Trastornos del Crecimiento/dietoterapia , Factor I del Crecimiento Similar a la Insulina/análisis , Factor I del Crecimiento Similar a la Insulina/metabolismo , Factor I del Crecimiento Similar a la Insulina/deficiencia , Estatura , Epilepsia/dietoterapia

RESUMEN

OBJECTIVE: Hormonal substitution with growth hormone in aged patients remains a debated research topic and is rarely initiated in clinical practice. This reluctance may originate from concerns about adverse effects and the uncritical use as an anti-aging agent. Nevertheless, beneficial effects for selected patients suffering from certain acute and chronic illnesses could justify its use at an advanced age. This systematic review analyzes randomized controlled studies of GH interventions in older patients with different comorbidities to assess both, beneficial and harmful effects. DESIGN: A systematic search strategy was implemented to identify relevant studies from PubMed, MEDLINE, and The Cochrane Library. INCLUSION CRITERIA: participants aged over 65 years, randomized controlled trials involving human growth hormone (GH) and presence of at least one additional comorbidity independent of a flawed somatotropic axis. RESULTS: The eight eligible studies encompassed various comorbidities including osteoporosis, frailty, chronic heart failure, hip fracture, amyotrophic lateral sclerosis and hemodialysis. Outcomes varied, including changes in body composition, physical performance, strength, bone mineral density, cardiovascular parameters, quality of life and housing situation. Study protocols differed greatly in GH application frequency (daily, 2nd day or 3×/week), doses (0.41 mg-2.6 mg; mean 1.3 mg per 60 kg patient) and duration (1-12 months; mean 7 months). Mild dose-related side effects were reported, alongside noticeable positive impacts particularly on body composition, functionality, and quality of life. CONCLUSION: Despite limited evidence, GH treatment might offer diverse benefits with few adverse effects. Further research with IGF-I dependent indication and clear outcomes, incorporating IGF-I dependent GH titration in older adults is warranted.

Asunto(s)

Envejecimiento , Hormona de Crecimiento Humana , Anciano , Humanos , Comorbilidad , Hormona del Crecimiento , Hormona de Crecimiento Humana/efectos adversos , Hormona de Crecimiento Humana/uso terapéutico , Factor I del Crecimiento Similar a la Insulina , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Envejecimiento/patología

RESUMEN

OBJECTIVE: Children with growth hormone deficiency (GHD) face multiple challenges that can negatively impact the transition from pediatric to adult endocrinology care. For children with GHD resulting from brain cancer or its treatment, the involvement of oncology care providers and possible disease-related comorbidities add further complexity to this transition. DESIGN: An advisory board of pediatric and adult endocrinologists was convened to help better understand the unique challenges faced by childhood cancer survivors with GHD, and discuss recommendations to optimize continuity of care as these patients proceed to adulthood. Topics included the benefits and risks of growth hormone (GH) therapy in cancer survivors, the importance of initiating GH replacement therapy early in the patient's journey and continuing into adulthood, and the obstacles that can limit an effective transition to adult care for these patients. RESULTS/CONCLUSIONS: Some identified obstacles included the need to prioritize cancer treatment over treatment for GHD, a lack of patient and oncologist knowledge about the full range of benefits provided by long-term GH administration, concerns about tumor recurrence risk in cancer survivors receiving GH treatment, and suboptimal communication and coordination (e.g., referrals) between care providers, all of which could potentially result in treatment gaps or even complete loss of follow-up during the care transition. Advisors provided recommendations for increasing education for patients and care providers and improving coordination between treatment team members, both of which are intended to help improve continuity of care to maximize the health benefits of GH administration during the critical period when childhood cancer survivors transition into adulthood.

Asunto(s)

Neoplasias Encefálicas , Supervivientes de Cáncer , Enanismo Hipofisario , Hormona de Crecimiento Humana , Hipopituitarismo , Adulto , Niño , Humanos , Encéfalo , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/terapia , Hormona del Crecimiento/uso terapéutico , Hormona de Crecimiento Humana/deficiencia , Transferencia de Pacientes

RESUMEN

Patients with Aarskog-Scott syndrome (AAS) have short stature, facial anomalies, skeletal deformities, and genitourinary malformations. FYVE, RhoGEF, and PH domain-containing 1 (FGD1) is the only known causative gene of AAS. However, the diagnosis of AAS remains difficult, and specific treatments are still absent. Patients suspected with AAS were recruited, and clinical information was collected. Genetic testing and functional analysis were carried out for the diagnosis. By literature review, we summarized the clinical and genetic characteristics of FGD1-related AAS and analyzed the genotype-phenotype correlation. Five patients were recruited, and four novel FGD1 variants were identified. The diagnosis of AAS was confirmed by genetic analysis and functional study. Three patients treated with growth hormone showed improved heights during the follow-up period. By literature review, clinical features of AAS patients with FGD1 variants were summarized. Regarding FGD1 variations, substitutions were the most common form, and among them, missense variants were the most frequent. Moreover, we found patients with drastic variants showed higher incidences of foot and genitourinary malformations. Missense variants in DH domain were related to a lower incidence of cryptorchidism.   Conclusion: We reported four novel pathogenic FGD1 variations in AAS patients and confirmed the efficacy and safety of growth hormone treatment in FGD1-related AAS patients with growth hormone deficiency. Additionally, our literature review suggested the crucial role of DH domain in FGD1 function. What is Known: • Aarskog-Scott syndrome is a rare genetic disease, and the only known cause is the variant in FGD1 gene. The typical clinical manifestations of AAS include facial, skeletal, and urogenital deformities and short stature. What is New: • We reported four novel FGD1 variants and reported the treatment of growth hormone in FGD1-related AAS patients. Our genotype-phenotype correlation analysis suggested the crucial role of DH domain in FGD1 function.

Asunto(s)

Anomalías Múltiples , Cara , Enfermedades Genéticas Ligadas al Cromosoma X , Genitales Masculinos , Factores de Intercambio de Guanina Nucleótido , Niño , Preescolar , Femenino , Humanos , Masculino , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Enanismo/genética , Enanismo/diagnóstico , Enanismo/tratamiento farmacológico , Cara/anomalías , Estudios de Asociación Genética , Genitales Masculinos/anomalías , Factores de Intercambio de Guanina Nucleótido/genética , Deformidades Congénitas de la Mano/genética , Deformidades Congénitas de la Mano/diagnóstico , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/diagnóstico , Fenotipo , Dermatosis del Cuero Cabelludo/genética , Dermatosis del Cuero Cabelludo/diagnóstico , Dermatosis del Cuero Cabelludo/tratamiento farmacológico , Dermatosis del Cuero Cabelludo/congénito , Anomalías Urogenitales/genética , Anomalías Urogenitales/diagnóstico

RESUMEN

OBJECTIVES: This prospective multicenter study aimed (1) to examine changes in parent-reported health-related quality of life (HRQOL) of children with short stature and the effects of the children's condition on parents themselves within the first year of human growth hormone (hGH) treatment and (2) to predict effects on parents based on main and interaction effects of children's HRQOL and increase in height. METHODS: A total of 110 parents of children aged 4-18 years, diagnosed with idiopathic growth hormone deficiency, small for gestational age, or idiopathic short stature, were recruited from 11 participating German pediatric endocrinologists and asked to fill out the short stature-specific Quality of Life in Short Stature Youth (QoLISSY) Questionnaire before hGH treatment was initiated and one year later. RESULTS: Negative effects of the children's short stature on the parents decrease over time, independent of diagnosis and treatment status. Furthermore, treatment status and height increase moderated the links between children's improved HRQOL as perceived by their parents and decreased caregiving burden. CONCLUSIONS: Based on the children's improved HRQOL and the parent's decrease in caregiving burden, patient-reported outcomes that consider parental and child's perspectives should be considered when deciding on hGH treatment for children.

Asunto(s)

Enanismo Hipofisario , Hormona de Crecimiento Humana , Niño , Adolescente , Humanos , Calidad de Vida , Estudios Prospectivos , Estatura , Enanismo Hipofisario/diagnóstico , Enanismo Hipofisario/tratamiento farmacológico , Encuestas y Cuestionarios , Padres , Hormona de Crecimiento Humana/uso terapéutico

RESUMEN

BACKGROUND: Recombinant human growth hormone (rhGH) therapy is beneficial for children with Prader-Willi syndrome (PWS) in improving short stature and metabolism, but the effect of early rhGH treatment on respiratory and sleep parameters for PWS children under three years old remains elusive. Thus, this study aimed to investigate the impact of rhGH treatment on sleep-related breathing disorders (SRBDs) for toddlers with PWS. METHODS: A total of 17 age-matched PWS patients receiving rhGH treatment (rhGH group) and 17 control individuals not receiving rhGH treatment (non-rhGH group) were recruited for this study between October 2018 and January 2023. Data related to polysomnography-polygraphy (PSG) and serum levels of insulin-like growth factor (IGF-1) and insulin-like growth factor binding protein 3 (IGFBP-3) were collected. RESULTS: The mean age in the rhGH group was 20.76 ± 9.22 months, which was comparable to that of the non-rhGH group (25.23 ± 13.81 months). The demographic and anthropometric parameters were similar across the two groups after 52 weeks of treatment. Administration of rhGH to toddlers did not exert adverse effects on the obstructive apnea-hypopnea index (OAHI), central apnea index (CAI), oxygen desaturation index (ODI), mean percutaneous oxygen saturation (SpO2), lowest SpO2, duration when SpO2 is lower than 90%, or proportion of the patients with SpO2 lower than 90%. Furthermore, the increased IGF-1 z-score and IGFBP-3 level did not worsen SRBDs. CONCLUSION: Treatment with rhGH for 52 weeks on young toddlers with PWS showed no deleterious effects on SRBDs. This shed more light on the importance of initiating rhGH therapy early in PWS patients.

Asunto(s)

Hormona de Crecimiento Humana , Síndrome de Prader-Willi , Humanos , Preescolar , Lactante , Hormona de Crecimiento Humana/uso terapéutico , Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina , Factor I del Crecimiento Similar a la Insulina , Síndrome de Prader-Willi/complicaciones , Síndrome de Prader-Willi/tratamiento farmacológico , Estudios Retrospectivos , Sueño

RESUMEN

Although the coronavirus disease 2019 (COVID-19) pandemic accelerated the adoption and expansion of telemedicine worldwide, little is known about the transition to home-based care for children. This study aims to investigate the facilitators and barriers to the transition from outpatient clinic visits to home-based check-ups (HBCU), for children being treated with growth hormone. A mixed-methods study was performed at Amalia Children's Hospital (Radboud University Medical Centre, Nijmegen), consisting of questionnaires and semi-structured and focus group interviews. For the quantitative part, the Measurement Instrument for Determinants of Innovation (MIDI) was utilised to investigate the facilitators and barriers for the 81 participants regarding the transition to HBCU. The MIDI questionnaire is comprised of four domains: the innovation-, user-, organisation-, and the socio-political scale. Descriptive statistics were performed for analysing the questionnaires. For the qualitative part, interviews with 10 participants derived from the questionnaire and the two focus group interviews were conducted, to gain more in-depth information about the research topic, until data saturation was reached. The interviews were analysed by using the reflective thematic approach, starting with deductive coding and followed by inductive coding. Several facilitators were recognised in our study: procedural clarity, self-efficacy, convenience, patient-centred care, increased accuracy in height measurements, social support, client/patient satisfaction/cooperation, patient-centred care, the flexibility and adaptivity of HBCU, physical start-up period of HBCU, and a potential decrease in healthcare costs. However, several barriers were also noted in our study: poor compatibility with current practice, lack of consultation within the team, feeling of being less controlled by physicians, unsettledness of the organisation, an increased workload for the staff, and insufficient information communication technology (ICT) facilities. CONCLUSION: This study revealed that HBCU have considerable benefits for both patients and healthcare professionals, from the standpoint of innovation, user, and socio-political points of view. The identified facilitators and barriers to HBCU should be taken into account when further steps of implementing HBCU are considered. WHAT IS KNOWN: • The Corona-Virus-Disease 2019 (COVID-19) pandemic has had an immense impact on health care worldwide. A substantial amount of the outpatient clinic visits for children treated with growth hormone was, as a result of the pandemic, transferred to online consultation. Transitioning paediatric growth hormone treatment to the home setting may be favorable for children and their parents/caregivers) as well for healthcare professionals. • Insights regarding facilitators and barriers is vital for the successful implementation and adoption of home-care technologies. WHAT IS NEW: • To our knowledge, we are first to report on and explicit the facilitators and barriers of the transition to home-based check-ups, via online consultation for children being treated with growth hormone. • Both children and healthcare professionals reported major facilitators and some minor barriers to the transition to home-based check-ups, illustrating their potential value. These facilitators and barriers should be considered while working towards implementation of home-based check-ups.

Asunto(s)

COVID-19 , Hormona del Crecimiento , Humanos , Niño , Personal de Salud , Instituciones de Atención Ambulatoria , Grupos Focales , Investigación Cualitativa

RESUMEN

RATIONALE: Children born small for gestational age (SGA) not showing catch-up during the first two years of life reportedly show an impaired growth rate and adult height, as well as a worse metabolic outcome, mainly in terms of glycemic and lipid profile, compared to general population. In SGA children with short stature, treatment with recombinant growth hormone (GH) is currently recommended until adolescence; therefore, it may last long-term. STUDY METHODS: The aim of the current study was to evaluate the auxological and metabolic effects and the safety of long-term recombinant GH treatment in SGA children. The study included 15 SGA children (5 F, 10 M; mean age: 6.78 yrs) treated with GH for at least 48 months. Growth and metabolic parameters, including glycemic and lipid profile, transaminases, and urycemia, were collected every six months. RESULTS: Compared to baseline, SGA children showed a significant improvement in height, weight, and growth rate after four yaers of treatment with GH (p ≤ 0.002), being already evident after six months of treatment (p < 0.001). Noteworthy, patients showed a constant, significant improvement in height throughout the treatment, as it was significantly higher at each follow-up compared to the previous one, until 42 months of treatment, except at 30 months of treatment (p < 0.001 T6VST12; p < 0.01 T12VST18, T18VST24; p < 0.05 T30VST36, T36VST42). Considering metabolic parameters, compared to baseline, a recurring increase in glycemia (p ≤ 0.028 vs T30, T36, and T48) and decrease in AST (p ≤ 0.035 vs T36, T42, and T48) and an occasional decrease in LDL cholesterol (p ≤ 0.04 vs T24 and T42) and triglycerides (p = 0.008 vs T18) and increase in urycemia (p = 0.034 vs T42). Considering safety profile, treatment was well tolerated, as the most frequently reported adverse event was poor compliance (20%); no hyperglycemia, hypercholesterolemia or hyperstransaminasemia occurred throughout the treatment, CONCLUSIONS: Long-term GH treatment showed to be effective in improving height and growth rate in SGA children, with a positive impact of metabolic profile and a safety profile, although glycemia should be carefully monitored over time.

Asunto(s)

Hormona del Crecimiento , Hormona de Crecimiento Humana , Niño , Humanos , Estatura , Edad Gestacional , Recién Nacido Pequeño para la Edad Gestacional , Lípidos , Estudios Retrospectivos

RESUMEN

CONTEXT: Increased cerebrovascular morbidity was reported in adults born small for gestational age (SGA) who were treated with growth hormone (GH) during childhood compared to the general population. However, previous studies did not have an appropriate control group, which is a major limitation. OBJECTIVE: To study cerebrovascular abnormalities (aneurysms, previous intracerebral hemorrhages and microbleeds) using magnetic resonance imaging (MRI) in adults born SGA at 12 years after cessation of childhood GH treatment (SGA-GH) compared to appropriate controls. METHODS: In this single-center, prospective study, brain MRIs were performed between May 2016 and December 2020 on a 3T MRI system. MRI images were scored by 2 neuroradiologists who were blinded to patient groupings. Participants included adults born SGA previously treated with GH and 3 untreated control groups: adults born SGA with persistent short stature (SGA-S), adults born SGA with spontaneous catch-up growth to a normal height (SGA-CU) and adults born appropriate for gestational age with a normal height (AGA). The intervention was long-term GH treatment during childhood and the main outcome measure was cerebrovascular abnormalities. RESULTS: A total of 301 adults were investigated. Aneurysms were found in 6 adults: 3 (3.6%) SGA-GH, 1 (2.9%) SGA-S and 2 (2.2%) AGA adults, without differences between SGA-GH adults and the controls. Previous intracerebral hemorrhages were only found in 2 SGA-S adults (4.8%). Microbleeds were found in 17 adults: 4 (4.3%) SGA-GH, 4 (9.5%) SGA-S, 3 (4.3%) SGA-CU and 6 (6.3%) AGA adults, without differences between SGA-GH adults and the controls. CONCLUSION: Our findings suggest that SGA-GH adults at 12 years after GH cessation have no increased prevalence of cerebrovascular abnormalities compared to appropriate controls. Further research is needed to confirm our findings.

Asunto(s)

Aneurisma , Hormona de Crecimiento Humana , Recién Nacido , Adulto , Femenino , Humanos , Hormona del Crecimiento , Estudios Prospectivos , Estatura , Hormona de Crecimiento Humana/efectos adversos , Recién Nacido Pequeño para la Edad Gestacional , Hemorragia Cerebral

RESUMEN

INTRODUCTION: Schaaf-Yang syndrome (SYS) is a rare neurodevelopmental disorder caused by truncating mutations of the MAGEL2 gene, located in the Prader-Willi syndrome (PWS) region. PWS and SYS have phenotypic overlap. Patients with SYS are often treated with growth hormone (GH), but evidence for the effectiveness of the treatment in patients with SYS is limited. METHODS: This study describes 7 children with SYS. We studied their phenotype, genotype, and the effect of GH treatment on height and body mass index (BMI) during 4 years and on body composition during 1 year. RESULTS: All patients had a normal birth weight. Most patients had hypotonia and feeding difficulties after birth (86%). Full-scale IQ ranged from <50 to 92. All patients above the age of 2 years had psycho-behavioral problems. There were no apparent correlations between the phenotype and the location of the defect in the MAGEL2 gene. Mean (95% CI) height SDS increased significantly from -1.74 (-3.55; 0.07) at start to -0.05 (-1.87; 1.77) after 4 years of GH treatment. Mean (95% CI) BMI SDS decreased significantly from 2.01 (1.02; 3.00) to 1.22 (0.18; 2.26) after 6 months and remained the same during the rest of the follow-up. Fat mass percentage SDS decreased and lean body mass did not change during 1 year of treatment in 3 patients. CONCLUSION: Patients presented with a phenotype of hypotonia, respiratory insufficiency, and feeding difficulties after birth, endocrine disorders, intellectual disability, and behavioral problems. Treatment with GH significantly improved height SDS and BMI over the course of 4 years.

Asunto(s)

Trastornos de los Cromosomas , Discapacidades del Desarrollo , Facies , Hormona de Crecimiento Humana , Hipopituitarismo , Trastornos de Impronta , Niño , Preescolar , Humanos , Hormona de Crecimiento Humana/uso terapéutico , Hormona de Crecimiento Humana/genética , Péptidos y Proteínas de Señalización Intracelular/genética , Proteínas Intrínsecamente Desordenadas/genética , Hipotonía Muscular/tratamiento farmacológico , Hipotonía Muscular/genética , Fenotipo , Síndrome de Prader-Willi/tratamiento farmacológico , Síndrome de Prader-Willi/genética

RESUMEN

INTRODUCTION: Tricho-rhino-phalangeal syndrome (TRPS) is a rare genetic disorder characterized by craniofacial and skeletal abnormalities, which is caused by variants in the TRPS1 gene. METHODS: Clinical information and follow-up data were collected. Whole-exome sequencing (WES) was performed for variants and validated by Sanger sequencing. Bioinformatic analysis was performed to predict the pathogenicity of the identified variant. Moreover, wild-type and mutated TRPS1 vectors were constructed and transfected into human embryonic kidney (HEK) 293T cells. Immunofluorescence experiments were performed to assess the localization and expression of the mutated protein. Western blot analysis and RT-qPCR were used to detect the expression of downstream genes. RESULTS: The affected family members had typical craniofacial phenotype including sparse lateral eyebrows, pear-shaped nasal tip, and large prominent ears, plus skeletal abnormalities including short stature and brachydactyly. WES and Sanger sequencing identified the TRPS1 c.880_882delAAG variant in affected family members. In vitro functional studies showed that the TRPS1 variant did not affect the cellular localization and the expression of TRPS1, but the transcriptional repression effect of the TRPS1 on the RUNX2 and STAT3 was disturbed. The proband and his brother have been treated with growth hormone (GH) for 2 years until now, and we have observed the improvement of the linear growth in both. CONCLUSIONS: The variant of c.880_882delAAG in TRPS1 was responsible for the pathogenesis of the Chinese family with TRPS I. The treatment of GH could be beneficial for the height outcome in TRPS I patients, and earlier initiation and longer duration of the therapy in prepubertal or early pubertal stage could be associated with better height outcomes.

Asunto(s)

Proteínas de Unión al ADN , Dedos/anomalías , Enfermedades del Cabello , Síndrome de Langer-Giedion , Nariz/anomalías , Masculino , Humanos , Proteínas de Unión al ADN/genética , Proteínas Represoras/genética , Síndrome de Langer-Giedion/tratamiento farmacológico , Síndrome de Langer-Giedion/genética , Síndrome de Langer-Giedion/patología , Síndrome , Hormona del Crecimiento , Biología Molecular , China

RESUMEN

Introduction Pycnodysostosis is a rare osteosclerotic skeletal dysplasia; its clinical features include short stature, characteristic facial features, increased bone fragility, and acro-osteolysis of the distal phalanx. Lack of clear guidelines for treatment and follow-up in rare diseases such as pycnodysostosis with growth hormone (GH) deficiency poses a difficulty for the clinician. This study aims to identify clinical, radiological, and endocrine findings of patients with pycnodysostosis focusing on the first year of recombinant human growth hormone (rhGH) treatment response. The eminence of this study is that it presents clinical experience with rhGH, providing an approach for future similar cases. Methods Three girls and two boys from three different families diagnosed with pycnodysostosis via clinical, radiological, and genetic evaluation followed up in the pediatric endocrinology clinic between 2022 and 2023 were enrolled in this study. Clinical findings, anthropometric measurements (weight, height, body mass index [BMI]), and laboratory, radiological, and genetic examinations were evaluated retrospectively. Participants were evaluated for GH deficiency using L-DOPA and clonidine tests if growth rate was below -2 standard deviation score (SDS) for gender and age after one-year follow-up. Results Complaints on admission were short stature (80%) and recurrent bone fractures (20%). Characteristic facial features and brachydactyly were seen in all the patients. Median height SDS on admission was -3.0 (range: -1.9 to -3.8). Median height SDS on last clinic visit was -3.2 (range: -1.7 to -4.2) at a median age of 8 years (range: 3.5-14 years). BMI was normal in four patients, while one was overweight. Bone mineral densitometry z-score was high, and two patients had bone fractures following minor trauma, while one had recurrent fractures. Two siblings (first and second cases) and the third case were diagnosed with GH deficiency, and anterior pituitary hormones were normal otherwise. One had partial empty sella in hypophyseal magnetic resonance imaging. rhGH (33 mcg/kg/day, subcutaneously) was started. Growth rate of the first, second, and third cases increased from 3.3, 3.1, 3.9 to 5, 4.3, 7.2 cm/year, respectively. Prior to rhGH, two had adenoid hypertrophy which was stable following rhGH. Growth rate follow-up of the fourth case continues, while the fifth case, the only participant who has reached adult height, has normal height according to age and gender normative. Conclusion Although rare, pycnodysostosis should not be overlooked in a patient with characteristic facial features, disproportionate short stature, and recurrent fractures. GH deficiency should be evaluated early if growth rate is declining. rhGH may restore growth rate and the possibility of catch-up in growth in patients with pycnodysostosis and GH deficiency. Hence, after first year of rhGH, growth rate of patients with pycnodysostosis is lower when compared to other etiologies of GH deficiency.