RESUMO
The geriatric failure to thrive, a controversial French concept not present in the international literature, was first characterized by Jean Carrié in 1956. It is described as a process of aging and physical and psychological decline associated with advanced age, manifesting as a pronounced overall deterioration. In this case report, we present the case of an 88-year-old patient, admitted to a general medicine service for geriatric failure to thrive, whose management eventually leads to the diagnosis of endocarditis with digestive cancer complicated by a characterized depressive episode. This case prompts us to consider the geriatric failure to thrive with extreme caution and challenges the legitimacy of such a diagnosis in the context of an aging population and the progress of medical sciences.
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Insuficiência de Crescimento , Humanos , Idoso de 80 Anos ou mais , Insuficiência de Crescimento/etiologia , Masculino , Endocardite/diagnóstico , FemininoRESUMO
PURPOSE: Congenital diaphragmatic hernia (CDH) affects 1 in 3000-5000 newborns. In survivors, long-term complications include gastroesophageal reflux (GER), feeding difficulties, and failure to thrive. Data from the parents' perspective remain scarce. This study aims to report the prevalence and impact of feeding difficulties on CDH families after discharge. METHODS: National web-based survey amongst families with CDH infants in 2021. RESULTS: Caregivers of 112 CDH survivors participated. The baseline characteristics were representative with 54 % male, 83 % left-sided CDH, prenatal diagnosis in 83 %, and 34 % requiring extracorporeal membrane oxygenation. Most infants (81 %) were discharged within three months, with 62 % feeding by mouth, and 30 % requiring a feeding tube. Persisting feeding difficulties were experienced by 73 %, GER being the most common (66 %), followed by insufficient weight gain (64 %). After discharge, 41 % received medical support for failure to thrive. The primary-care pediatrician was consulted most frequently for information (61 %) and treatment of feeding difficulties (74 %). Therapeutic success was reported in 64 %. A cessation of symptoms was achieved in 89 % within three years. CONCLUSION: The majority of CDH infants had persistent feeding difficulties. This survey highlights the impact surrounding feeding problems on CDH families. Further studies and support systems are needed to raise the quality of life in CDH infants and their families.
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Hérnias Diafragmáticas Congênitas , Pais , Humanos , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/terapia , Masculino , Feminino , Recém-Nascido , Alta do Paciente , Lactente , Insuficiência de Crescimento/etiologia , Insuficiência de Crescimento/epidemiologia , Insuficiência de Crescimento/terapiaRESUMO
Trithorax-related H3K4 methyltransferases, KMT2C and KMT2D, are critical epigenetic modifiers. Haploinsufficiency of KMT2C was only recently recognized as a cause of neurodevelopmental disorder (NDD), so the clinical and molecular spectrums of the KMT2C-related NDD (now designated as Kleefstra syndrome 2) are largely unknown. We ascertained 98 individuals with rare KMT2C variants, including 75 with protein-truncating variants (PTVs). Notably, â¼15% of KMT2C PTVs were inherited. Although the most highly expressed KMT2C transcript consists of only the last four exons, pathogenic PTVs were found in almost all the exons of this large gene. KMT2C variant interpretation can be challenging due to segmental duplications and clonal hematopoesis-induced artifacts. Using samples from 27 affected individuals, divided into discovery and validation cohorts, we generated a moderate strength disorder-specific KMT2C DNA methylation (DNAm) signature and demonstrate its utility in classifying non-truncating variants. Based on 81 individuals with pathogenic/likely pathogenic variants, we demonstrate that the KMT2C-related NDD is characterized by developmental delay, intellectual disability, behavioral and psychiatric problems, hypotonia, seizures, short stature, and other comorbidities. The facial module of PhenoScore, applied to photographs of 34 affected individuals, reveals that the KMT2C-related facial gestalt is significantly different from the general NDD population. Finally, using PhenoScore and DNAm signatures, we demonstrate that the KMT2C-related NDD is clinically and epigenetically distinct from Kleefstra and Kabuki syndromes. Overall, we define the clinical features, molecular spectrum, and DNAm signature of the KMT2C-related NDD and demonstrate they are distinct from Kleefstra and Kabuki syndromes highlighting the need to rename this condition.
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Anormalidades Múltiplas , Deleção Cromossômica , Cromossomos Humanos Par 9 , Anormalidades Craniofaciais , Metilação de DNA , Proteínas de Ligação a DNA , Face , Doenças Hematológicas , Deficiência Intelectual , Transtornos do Neurodesenvolvimento , Doenças Vestibulares , Humanos , Anormalidades Múltiplas/genética , Doenças Vestibulares/genética , Deficiência Intelectual/genética , Face/anormalidades , Face/patologia , Proteínas de Ligação a DNA/genética , Masculino , Feminino , Doenças Hematológicas/genética , Transtornos do Neurodesenvolvimento/genética , Anormalidades Craniofaciais/genética , Cromossomos Humanos Par 9/genética , Criança , Metilação de DNA/genética , Pré-Escolar , Proteínas de Neoplasias/genética , Adolescente , Hipertricose/genética , Mutação , Insuficiência de Crescimento/genética , Histona-Lisina N-Metiltransferase/genética , Cardiopatias CongênitasRESUMO
Pseudohypoaldosteronism type 1 is a rare congenital autosomal recessive disorder, characterised by failure of receptor response to aldosterone. It is caused by mutation in SCNN1A gene with clinical features like failure to thrive in infancy, hyponatraemia, hyperkalaemia and metabolic acidosis. We present a male infant with seizures, hyperkalaemia and with failure to thrive, diagnosed at day 6 of life. The baby required repeated correction for hyperkalaemia; hence, after ruling out treatable causes for hyperkalaemia, exonerated sequencing was done which showed pathogenic mutation for cystic fibrosis and recessive mutation for pseudohypoaldosteronism. But the child was clinically in favour of pseudohypoaldosteronism. Hence, features of pseudohypoaldosteronism predominate cystic fibrosis; they both may coexist.
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Fibrose Cística , Hiperpotassemia , Pseudo-Hipoaldosteronismo , Humanos , Pseudo-Hipoaldosteronismo/genética , Pseudo-Hipoaldosteronismo/diagnóstico , Pseudo-Hipoaldosteronismo/complicações , Fibrose Cística/complicações , Fibrose Cística/genética , Masculino , Hiperpotassemia/etiologia , Recém-Nascido , Canais Epiteliais de Sódio/genética , Insuficiência de Crescimento/etiologia , Convulsões/etiologia , MutaçãoRESUMO
A 4-month-old full-term female presented with growth faltering associated with progressive feeding difficulty, rash, abdominal distension, and developmental delays. She was found to have disconjugate gaze, abnormal visual tracking, mixed tone, bruising, and splenomegaly on examination. Initial workup was notable for thrombocytopenia and positive cytomegalovirus (CMV) immunoglobulin G and immunoglobulin M antibodies. She initially presented to the infectious diseases CMV clinic, where she was noted to have severe malnutrition, prompting referral to the emergency department for hospital admission to optimize nutrition with nasogastric tube feeding and facilitate additional evaluation. An active CMV infection with viruria and viremia was confirmed, but elements of her presentation and workup including brain magnetic resonance imaging were not consistent with isolated CMV infection. To avoid premature diagnostic closure, a multidisciplinary workup was initiated and ultimately established her diagnosis.
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Esplenomegalia , Trombocitopenia , Humanos , Feminino , Lactente , Esplenomegalia/etiologia , Esplenomegalia/diagnóstico por imagem , Trombocitopenia/diagnóstico , Infecções por Citomegalovirus/complicações , Infecções por Citomegalovirus/diagnóstico , Insuficiência de Crescimento/etiologia , Diagnóstico DiferencialRESUMO
AbstractMorning Report is a time-honored tradition where physicians-in-training present cases to their colleagues and clinical experts to collaboratively examine an interesting patient presentation. The Morning Report section seeks to carry on this tradition by presenting a patient's chief concern and story, inviting the reader to develop a differential diagnosis and discover the diagnosis alongside the authors of the case. This report examines the story of a 15-month-old with faltering growth and short stature. Using questions, physical examination, and testing, an illness script for the presentation emerges. As the clinical course progresses, the differential is refined until a diagnosis is made.
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Transtornos do Crescimento , Humanos , Lactente , Diagnóstico Diferencial , Transtornos do Crescimento/diagnóstico , Masculino , Feminino , Insuficiência de Crescimento/diagnóstico , Insuficiência de Crescimento/etiologiaRESUMO
The aetiology of failure to thrive (FTT) in children is broad, of which some conditions are extremely rare. It is important to consider these rarer conditions, especially in the setting of other concerning signs/symptoms or when there is no improvement with conventional treatment. In this case report we highlight such a rare condition-chylomicron retention disease (CRD) as an aetiology of FTT. CRD often presents with non-specific symptoms, resulting in delayed diagnosis which is established by genetic workup and histology from small intestinal biopsies. Despite being rare, CRD needs to be considered as one of the differential diagnoses after ruling out the more common causes of FTT.
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Insuficiência de Crescimento , Síndromes de Malabsorção , Humanos , Insuficiência de Crescimento/etiologia , Síndromes de Malabsorção/diagnóstico , Síndromes de Malabsorção/complicações , Diagnóstico Diferencial , Hipobetalipoproteinemias/genética , Hipobetalipoproteinemias/diagnóstico , Hipobetalipoproteinemias/complicações , Masculino , Lactente , Feminino , Intestino Delgado/patologia , BiópsiaRESUMO
BACKGROUND: RASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually. METHODS: We conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers. RESULTS: We included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio-facio-cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies. CONCLUSIONS: Our systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.
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Transtorno do Espectro Autista , Síndrome de Costello , Cardiopatias Congênitas , Neurofibromatose 1 , Síndrome de Noonan , Humanos , Transtorno do Espectro Autista/genética , Síndrome de Noonan/genética , Cardiopatias Congênitas/genética , Síndrome de Costello/genética , Insuficiência de Crescimento/genética , Neurofibromatose 1/genéticaRESUMO
BACKGROUND: Rauch-Steindl syndrome (RAUST) is a very rare genetic syndrome caused by a pathogenic variant in NSD2 on chromosome 4p16.3. Although NSD2 was previously thought to be the major gene in Wolf-Hirschhorn syndrome (WHS), a contiguous gene syndrome of chromosome 4p16.3 deletion, RAUST has been found to present different facial and clinical features from WHS. In this study, we report the details of two newly diagnosed individuals with RAUST in order to better understand the molecular and clinical features of RAUST. METHODS: Whole-genome sequencing was performed on two individuals with psychomotor delay and growth failure. Detailed clinical evaluation of growth parameters, craniofacial features, electroencephalogram (EEG), magnetic resonance imaging of the brain, and developmental assessment were performed. RESULTS: Both individuals had de novo truncating variants in NSD2. One had a novel variant (c.2470C>T, p.Arg824*), and the other had a recurrent variant (c.4028del, p.Pro1343Glnfs*49). Both exhibited characteristic RAUST facial features, growth failure, and mild psychomotor delay. A novel finding of RAUST was seen in individual 2, a Chiari malformation type 1, and both showed delayed bone age. They lacked common WHS features such as congenital heart defects, cleft lip/palate, and seizures (EEG with abnormal findings). CONCLUSION: We present a novel variant and clinical presentations of RAUST, expand the molecular and clinical diversity of RAUST, and improve our understanding of this rare syndrome, which is distinct from WHS. Further researches are needed on more RAUST cases and on functional analysis of NSD2.
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Fenda Labial , Fissura Palatina , Síndrome de Wolf-Hirschhorn , Humanos , Deleção Cromossômica , Fenda Labial/genética , Fissura Palatina/genética , Insuficiência de Crescimento/genética , Convulsões/genética , Síndrome de Wolf-Hirschhorn/genética , Síndrome de Wolf-Hirschhorn/patologiaRESUMO
We present the case of a 20-month-old girl with Schimmelpenning-Feuerstein-Mims (SFM) syndrome with extensive head, neck, and torso skin involvement successfully managed with topical trametinib. Trametinib interferes downstream of KRAS and HRAS in the MAPK signaling pathway, of which KRAS was implicated in our child's pathogenic variant. Although other dermatologic conditions have shown benefit from oral trametinib, its topical use has not been well reported. Our patient showed benefit from the use of twice-daily topical trametinib, applied to the epidermal and sebaceous nevi over a 16-month period, leading to decreased pruritus and thinning of the plaques.
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Piridonas , Pirimidinonas , Neoplasias Cutâneas , Humanos , Piridonas/uso terapêutico , Piridonas/administração & dosagem , Feminino , Pirimidinonas/uso terapêutico , Pirimidinonas/administração & dosagem , Lactente , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologia , Nevo/tratamento farmacológico , Insuficiência de Crescimento/tratamento farmacológico , Administração Tópica , Anormalidades Múltiplas/tratamento farmacológico , Nevo Sebáceo de Jadassohn/tratamento farmacológico , Síndromes Neurocutâneas/tratamento farmacológico , Síndromes Neurocutâneas/diagnóstico , Anormalidades da Pele/tratamento farmacológico , Antineoplásicos/uso terapêutico , Anormalidades do Olho/tratamento farmacológico , Doenças da Imunodeficiência Primária/tratamento farmacológicoRESUMO
AIM: To differentiate phenotypic features of individuals with CDKL5 deficiency disorder (CDD) from those of individuals with other infantile-onset epilepsies. METHOD: We performed a retrospective cohort study and ascertained individuals with CDD and comparison individuals with infantile-onset epilepsy who had epilepsy gene panel testing. We reviewed records, updated variant classifications, and compared phenotypic features. Wilcoxon rank-sum tests and χ2 or Fisher's exact tests were performed for between-cohort comparisons. RESULTS: We identified 137 individuals with CDD (110 females, 80.3%; median age at last follow-up 3 year 11 months) and 313 individuals with infantile-onset epilepsies (156 females, 49.8%; median age at last follow-up 5 years 2 months; 35% with genetic diagnosis). Features reported significantly more frequently in the CDD group than in the comparison cohort included developmental and epileptic encephalopathy (81% vs 66%), treatment-resistant epilepsy (95% vs 71%), sequential seizures (46% vs 6%), epileptic spasms (66% vs 42%, with hypsarrhythmia in 30% vs 48%), regression (52% vs 29%), evolution to Lennox-Gastaut syndrome (23% vs 5%), diffuse hypotonia (72% vs 36%), stereotypies (69% vs 11%), paroxysmal movement disorders (29% vs 17%), cerebral visual impairment (94% vs 28%), and failure to thrive (38% vs 22%). INTERPRETATION: CDD, compared with other suspected or confirmed genetic epilepsies presenting in the first year of life, is more often characterized by a combination of treatment-resistant epilepsy, developmental and epileptic encephalopathy, sequential seizures, spasms without hypsarrhythmia, diffuse hypotonia, paroxysmal movement disorders, cerebral visual impairment, and failure to thrive. Defining core phenotypic characteristics will improve precision diagnosis and treatment.
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Encefalopatias , Epilepsia , Síndromes Epilépticas , Transtornos dos Movimentos , Espasmos Infantis , Estado Epiléptico , Feminino , Humanos , Masculino , Eletroencefalografia , Epilepsia/diagnóstico , Epilepsia/genética , Insuficiência de Crescimento , Hipotonia Muscular/genética , Proteínas Serina-Treonina Quinases/genética , Estudos Retrospectivos , Convulsões , Espasmo , Espasmos Infantis/diagnóstico , Espasmos Infantis/genética , Transtornos da VisãoRESUMO
AIM OF THE STUDY: Neonatal enterostomy is a known risk for growth failure. We hypothesized that episodes of inflammation may drive a catabolic state, exploring this by assessing serum biochemistry alongside growth trajectory in enterostomy patients. METHODS: A retrospective analysis of infants with histologically confirmed NEC from 01/2012-07/2021 in a tertiary neonatal surgical centre was performed. Change in weight-for-age Z-score (ΔZ) between stoma formation and closure was calculated. Serum CRP (C-reactive protein), urea, and creatinine levels were recorded and duration of elevated levels calculated as Area Under Curve (AUC). We examined for trends of serum levels rising together using intersecting moving averages. Spearman's correlation analysis was performed, while multivariable linear regression examined factors associated with ΔZ. RESULTS: 79 neonates were included. At stoma formation, median Z-score was -1.42 [range -4.73, +1.3]. Sixty-two patients (78 %) had a fall in Z-score during their time with a stoma, 16 (20 %) had a ΔZ less than -2. Urea AUC was significantly univariably correlated with ΔZ and remained statistically significant in a multivariable model (Exp(B) x 100 = -0.57[-1, -0.09]; p = 0.022). The number of biomarker peaks correlated significantly with ΔZ for urea (r = -0.25; p = 0.025) and CRP (r = -0.35; p = 0.0017) but not Creatinine (r = -0.21; p = 0.066). Analysing the number of peaks of any combination of variables coinciding was consistently significantly correlated negatively with ΔZ (r = -0.29 to -0.27; p ≤ 0.016 for all). CONCLUSION: Our data shows that infants who were more severely affected by growth failure had more frequent and severe uremia while they had a stoma (suggesting a catabolic state). Disturbances in urea were commonly associated with CRP, suggesting that inflammation is a significant factor in growth failure in these infants. These findings promote aggressive management of sepsis in these infants, as well as suggesting an earlier closure of stoma to minimise their "at-risk"' period.
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Enterocolite Necrosante , Enterostomia , Estomas Cirúrgicos , Recém-Nascido , Lactente , Humanos , Estudos Retrospectivos , Insuficiência de Crescimento/etiologia , Inflamação , Ureia , Enterocolite Necrosante/cirurgiaRESUMO
OBJECTIVE: To describe the growth trajectory of children with congenital diaphragmatic hernia (CDH) during the first year, to assess the risk factors for growth failure (GF) at 1 year and to determine nutritional intakes at discharge required for early optimal growth. DESIGN: Single-centre retrospective cohort study based on data from a structured follow-up programme. SETTING AND PATIENTS: All neonates with CDH (2013-2019) alive at discharge and followed up to age 1. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Weight-for-age z-score (WAZ) at birth, 3, 6 and 12 months of age; risk factors for GF at age 1; energy and protein intake of infants achieving early optimal growth. RESULTS: Sixty-three of 65 neonates who were alive at discharge were included. Seven (11%) had GF at 1 year and 3 (4.8%) had a gastrostomy tube. The mean WAZ decreased in the first 3 months before catching up at 1 year (-0.6±0.78). Children with a severe form or born preterm experienced a deeper loss (from -1.5 to -2 z-scores) with late and limited catch-up. The median energy intake required to achieve positive or null weight growth velocity differed significantly according to CDH severity, ranging from 100 kcal/kg/day (postnatal forms) to 139 kcal/kg/day (severe prenatal forms) (p=0.009). CONCLUSIONS: Growth patterns of CDH infants suggest that nutritional risk stratification and feeding practices may influence growth outcomes. Our results support individualised and active nutritional management based on CDH severity, with energy requirements as high as 140% of recommended intakes for healthy term infants.
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Hérnias Diafragmáticas Congênitas , Necessidades Nutricionais , Criança , Feminino , Humanos , Lactente , Recém-Nascido , Gravidez , Ingestão de Energia , Insuficiência de Crescimento , Estudos RetrospectivosRESUMO
Failure to thrive (FTT) is an inadequate growth in young children. It can increase the risk of overweight or obesity later in life. Patients with renal tubulopathies can present FTT due to solute losses in the urine. We aimed to test our hypothesis that children with tubulopathies have an increased risk of overweight and obesity due to rebound following FTT that could complicate these conditions. We enrolled 26 patients with tubulopathies and evaluated for the first time within the first 12 months of life (mean age: 4.8 months ± 2.6 SDS). FTT was evident in 17 out of 26 patients (65.4%). The mean age at the last follow-up was 14.1 years ± 5.5 SDS. The mean age at overweight/obesity onset was 9.0 years ± 3.6 SDS. The prevalence of overweight/obesity was 73.1% (19/26). Among the patients with FTT, 15 (88.2%) developed overweight/obesity compared to 4 out of the 9 patients (44.4%) without FFT (p = 0.028). The presence of FTT determined an OR for obesity/overweight of 9.4 (95% CI: 1.3-67.6; p = 0.026). FTT continued to be significantly associated with obesity/overweight also after adjustment for preterm birth and birth weight <10th percentile (OR = 23.3; 95% CI: 1.95-279.4; p = 0.01). In conclusion, in our series, patients with tubulopathies presented an increased risk of overweight/obesity due to the FTT that can complicate these conditions.
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Insuficiência de Crescimento , Nascimento Prematuro , Criança , Feminino , Humanos , Recém-Nascido , Pré-Escolar , Lactente , Adolescente , Insuficiência de Crescimento/epidemiologia , Insuficiência de Crescimento/etiologia , Sobrepeso/complicações , Sobrepeso/epidemiologia , Obesidade/complicações , Obesidade/epidemiologia , Peso ao Nascer , Redução de PesoRESUMO
Treatment-resistant epilepsy is among the most serious complications of cardiofaciocutaneous syndrome (CFCS), a rare disorder caused by germline variants in the RAS-MAPK signaling pathway. This study analyzed the clinical characteristics of epilepsy and response to anti-seizure medications (ASMs) in a multinational CFCS cohort. A caregiver survey provided data regarding seizure history, use of ASMs and other treatment approaches, adverse effects, caregiver perception of treatment response, and neurological disease burden impact among individuals with CFCS. Results from 138 survey responses were quantitatively analyzed in conjunction with molecular genetic results and neurological records. The disease burden impact of CFCS was higher among individuals with epilepsy (n = 74/138), especially those with more severe seizure presentation. Oxcarbazepine, a sodium-channel blocker, had the best seizure control profile with relatively infrequent adverse effects. The most commonly prescribed ASM, levetiracetam, demonstrated comparatively poor seizure control. ASM efficacy was generally similar for individuals with BRAF and MAP2K1 gene variants. The high proportion of patients with CFCS who experienced poor seizure control despite use of multiple ASMs highlights a substantial unmet treatment need. Prospective study of ASM efficacy and clinical trials of therapies to attenuate RAS-MAPK signaling may improve avenues for clinical management.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Displasia Ectodérmica , Epilepsia , Fácies , Insuficiência de Crescimento , Cardiopatias Congênitas , Humanos , Estudos Prospectivos , Epilepsia/tratamento farmacológico , Epilepsia/genética , Levetiracetam , Convulsões/tratamento farmacológico , Convulsões/genética , Anticonvulsivantes/uso terapêuticoRESUMO
OBJECTIVE: Cardio-facio-cutaneous syndrome (CFC) is a genetic disorder due to variants affecting genes coding key proteins of the Ras/MAPK signaling pathway. Among the different features of CFC, neurological involvement, including cerebral malformations and epilepsy, represents a common and clinically relevant aspect. Status epilepticus (SE) is a recurrent feature, especially in a specific subgroup of CFC patients with developmental and epileptic encephalopathy (DEE) and history of severe pharmacoresistant epilepsy. Here we dissect the features of SE in CFC patients with a particular focus on longitudinal magnetic resonance imaging (MRI) findings to identify clinical-radiological patterns and discuss the underlying physiopathology. METHODS: We retrospectively analyzed clinical, electroencephalogram (EEG), and MRI data collected in a single center from a cohort of 23 patients with CFC carrying pathogenic BRAF variants who experienced SE during a 5-year period. RESULTS: Seven episodes of SE were documented in 5 CFC patients who underwent EEG and MRI at baseline. MRI was performed during SE/within 72 hours from SE termination in 5/7 events. Acute/early post-ictal MRI findings showed heterogenous abnormalities: restricted diffusion in 2/7, focal area of pcASL perfusion change in 2/7, focal cortical T2/FLAIR hyperintensity in 2/7. Follow-up images were available for 4/7 SE. No acute changes were detected in 2/7 (MRI performed 4 days after SE termination). SIGNIFICANCE: Acute focal neuroimaging changes concomitant with ictal EEG focus were present in 5/7 episodes, though with different findings. The heterogeneous patterns suggest different contributing factors, possibly including the presence of focal cortical malformations and autoinflammation. When cytotoxic edema is revealed by MRI, it can be followed by permanent structural damage, as already observed in other genetic conditions. A better understanding of the physiopathology will provide access to targeted treatments allowing to prevent long-term adverse neurological outcome. PLAIN LANGUAGE SUMMARY: Cardio-facio-cutaneous syndrome is a genetic disorder that often causes prolonged seizures known as status epilepticus. This study has a focus on electroclinical and neuroimaging patterns in patients with cardio-facio-cutaneous syndrome. During these status epilepticus episodes, we found different abnormal brain imaging patterns in patients, indicating various causes like brain malformations and inflammation. Understanding these patterns could help doctors find specific treatments, protecting cardio-facio-cutaneous syndrome patients from long-term brain damage.
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Displasia Ectodérmica , Epilepsia , Fácies , Insuficiência de Crescimento , Cardiopatias Congênitas , Estado Epiléptico , Humanos , Proteínas Proto-Oncogênicas B-raf/genética , Estudos Retrospectivos , Estado Epiléptico/diagnóstico por imagem , Estado Epiléptico/genética , NeuroimagemRESUMO
Failure to thrive (FTT) is a DSM-5/ICD-10 diagnosis which describes infants and children who fail to grow within expected norms. The causes for poor growth are multifactorial and often include psychosocial factors. Social workers are important players in an interdisciplinary team approach to this diagnosis. This research and manuscript focus on the use of an integrated infant mental health pediatric model of practice, and outcomes for one case study. The article will review the social worker's role in the treatment of FTT, effective social work services provided in an integrated behavioral health approach, and a review of a cost-benefit analysis of treatment of FTT in a Primary Care Facility verses a hospital setting.
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Insuficiência de Crescimento , Serviço Social , Lactente , Humanos , Criança , Insuficiência de Crescimento/terapia , Insuficiência de Crescimento/diagnóstico , Insuficiência de Crescimento/etiologia , Assistentes SociaisRESUMO
INTRODUCTION: Patients with homozygous recessive mutations in STAT5B have severe progressive postnatal growth failure and insulin-like growth factor-I (IGF-I) deficiency associated with immunodeficiency and increased risk of autoimmune and pulmonary conditions. This report describes the efficacy and safety of recombinant human IGF-1 (rhIGF-1) in treating severe growth failure due to STAT5B deficiency. CASE PRESENTATION: Three siblings (P1, 4.4 year-old female; P2, 2.3 year-old male; and P3, 7 month-old female) with severe short stature (height SDS [HtSDS] -6.5, -4.9, -5.3, respectively) were referred to the Center for Growth Disorders at Cincinnati Children's Hospital Medical Center. All three had a homozygous mutation (p.Trp631*) in STAT5B. Baseline IGF-I was 14.7, 14.1, and 10.8 ng/mL, respectively (all < -2.5 SDS for age and sex), and IGFBP-3 was 796, 603, and 475 ng/mL, respectively (all < -3 SDS for age and sex). The siblings were started on rhIGF-1 at 40 µg/kg/dose twice daily subcutaneously (SQ), gradually increased to 110-120 µg/kg/dose SQ twice daily as tolerated. HtSDS and height velocity (HV) were monitored over time. RESULTS: Six years of growth data was utilized to quantify growth response in the two older siblings and 5 years of data in the youngest. Pre-treatment HVs were, respectively, 3.0 (P1), 3.0 (P2), and 5.2 (P3) cm/year. With rhIGF-1 therapy, HVs increased to 5.2-6.0, 4.8-7.1, and 5.5-7.4 cm/year, respectively, in the first 3 years of treatment, before they decreased to 4.7, 3.8, and 4.3 cm/year, respectively, at a COVID-19 pandemic delayed follow-up visit and with decreased treatment adherence. ΔHtSDS for P1 and P2 was +2.21 and +0.93, respectively, over 6 years, but -0.62 for P3 after 5 years and in the setting of severe local lipohypertrophy and suboptimal weight gain. P3 also experienced hypoglycemia that limited our ability to maintain target rhIGF-1 dosing. CONCLUSION: The response to rhIGF-1 therapy is less than observed with rhIGF-1 therapy for patients previously described with severe primary IGF-I deficiency, including patients with documented defects in the growth hormone receptor, but may still provide patients with STAT5B deficiency with an opportunity to prevent worsening growth failure.
Assuntos
Insuficiência de Crescimento , Transtornos do Crescimento , Fator de Crescimento Insulin-Like I , Peptídeos Semelhantes à Insulina , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Proteína 3 de Ligação a Fator de Crescimento Semelhante à Insulina , Fator de Crescimento Insulin-Like I/deficiência , Fator de Crescimento Insulin-Like I/uso terapêutico , Proteínas Recombinantes/uso terapêutico , Irmãos , Fator de Transcrição STAT5/genética , SíndromeRESUMO
Current clinical guidelines provide information about the diagnostic workup of children with growth failure. This mini-review focuses on the nutritional assessment, which has received relatively little attention in such guidelines. The past medical history, in particular a low birth size and early feeding problems, can provide information that can increase the likelihood of nutritional deficits or several genetic causes. The current medical history should include a dietary history and can thereby reveal a poorly planned or severely restricted diet, which can be associated with nutritional deficiencies. Children on a vegan diet should receive various nutritional supplements, but insufficient compliance has been reported in one-third of cases. While proper use of nutritional supplements in children consuming a vegan diet appears to be associated with normal growth and development, insufficient intake of supplements may impede growth and bone formation. Physical examination and analysis of height and weight over time can help differentiating between endocrine causes, gastrointestinal disorders, psychosocial problems, or underlying genetic conditions that prevent adequate nutritional intake. Laboratory screening should be part of the workup in every child with short stature, and further laboratory tests can be indicated if warranted by the dietary history, especially in children on a poorly planned vegan diet.