ABSTRACT
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.
Subject(s)
Failure to Thrive , Malabsorption Syndromes , Humans , Failure to Thrive/etiology , Malabsorption Syndromes/diagnosis , Malabsorption Syndromes/complications , Diagnosis, Differential , Hypobetalipoproteinemias/genetics , Hypobetalipoproteinemias/diagnosis , Hypobetalipoproteinemias/complications , Male , Infant , Female , Intestine, Small/pathology , BiopsySubject(s)
Failure to Thrive , Humans , Failure to Thrive/etiology , Failure to Thrive/diagnosis , Infant , Diagnosis, Differential , Male , FemaleABSTRACT
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.
Subject(s)
Autism Spectrum Disorder , Costello Syndrome , Heart Defects, Congenital , Neurofibromatosis 1 , Noonan Syndrome , Humans , Autism Spectrum Disorder/genetics , Noonan Syndrome/genetics , Heart Defects, Congenital/genetics , Costello Syndrome/genetics , Failure to Thrive/genetics , Neurofibromatosis 1/geneticsABSTRACT
Introducción: La mucopolisacaridosis de tipo III (MPS III), o síndrome de Sanfilippo, es un trastorno de almacenamiento lisosómico con características neurodegenerativas progresivas, predominante del sistema nervioso central. Su diagnóstico se basa en el cuadro clínico, y priman alteraciones en el neurodesarrollo y neuropsiquiátricas, incluso antes de la presencia de alteraciones fenotípicas. El análisis bioquímico para identificar el tipo de glucosaminoglucanos presente, la determinación enzimática y el estudio de genética molecular confirman la enfermedad. Casos clínicos: Se realiza la descripción clínica de ocho pacientes con diagnóstico de MPS III en Colombia, con síntomas iniciales en relación con retraso del desarrollo y trastornos comportamentales evidenciados entre los 3 y 8 años, asociado a facies toscas, cejas pobladas, hepatomegalia y pérdida auditiva progresiva en todos los casos. Uno de los pacientes presentó anomalías cardíacas; dos de ellos, epilepsia focal; y en uno se evidenció atrofia óptica. Todos presentaron alteraciones en las neuroimágenes con evidencia de pérdida del volumen parenquimatoso, atrofia del cuerpo calloso y adelgazamiento cortical; el diagnostico se realizó a través de estudios bioquímicos de cromatografía de glucosaminoglucanos y todos cuentan con un estudio genético confirmatorio. Conclusiones: La MPS III es un desafío diagnóstico, particularmente en pacientes con un curso atenuado de la enfermedad, debido al curso variable, síntomas neuropsiquiátricos tempranos inespecíficos y falta de características somáticas evidentes en comparación con otros tipos de MPS. Cuando se tiene el diagnóstico definitivo, es fundamental brindar atención interdisciplinaria para el paciente y la familia, y apoyar el tratamiento de los síntomas físicos, garantizando ofrecer el mejor cuidado posible y la mejor calidad de vida para el paciente y su familia, al tratarse de una condición neurodegenerativa.(AU)
Introduction: Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a lysosomal storage disease with progressive neurodegenerative features, predominantly affecting the central nervous system. Diagnosis is based on clinical features, with neurodevelopmental and neuropsychiatric alterations taking precedence, including over phenotype alterations. The disease is confirmed by biochemical analysis to identify the type of glycosaminoglycans present, enzyme assay and molecular genetic studies. Case reports: A clinical description was performed for eight patients diagnosed with MPS III in Colombia. Their initial symptoms were related to developmental delay and behavioural disorders presenting between 3 and 8 years of age, associated in all cases with coarse facial features, thick eyebrows, hepatomegaly and progressive hearing loss. One of the patients presented cardiac anomalies; two presented focal epilepsy; and one presented optic atrophy. They all presented neuroimaging alterations, with evidence of parenchymal volume loss, corpus callosum atrophy and cortical thinning; the diagnosis was performed by biochemical glycosaminoglycan chromatography studies, and all patients have a confirmatory genetic study. Conclusions: MPS III is a challenge for diagnosis, particularly in its early stages and in patients in which the course of the disease is attenuated. This is due to its variable course, non-specific early neuropsychiatric symptoms, and the absence of obvious somatic features compared to other types of MPS. After a definitive diagnosis has been made, interdisciplinary care must be provided for the patient and their family, and support given for the treatment of physical symptoms, ensuring the best possible care and quality of life for the patient and their family, as the condition is neurodegenerative.(AU)
Subject(s)
Humans , Male , Female , Child , Mucopolysaccharidosis II/history , Neurodegenerative Diseases , Failure to Thrive , Conduct Disorder , Heparitin Sulfate , Lysosomal Storage Diseases , Colombia , Neurology , Nervous System Diseases , Central Nervous SystemABSTRACT
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.
Subject(s)
Cleft Lip , Cleft Palate , Wolf-Hirschhorn Syndrome , Humans , Chromosome Deletion , Cleft Lip/genetics , Cleft Palate/genetics , Failure to Thrive/genetics , Seizures/genetics , Wolf-Hirschhorn Syndrome/genetics , Wolf-Hirschhorn Syndrome/pathologyABSTRACT
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.
Subject(s)
Pyridones , Pyrimidinones , Skin Neoplasms , Humans , Pyridones/therapeutic use , Pyridones/administration & dosage , Female , Pyrimidinones/therapeutic use , Pyrimidinones/administration & dosage , Infant , Skin Neoplasms/drug therapy , Skin Neoplasms/pathology , Nevus/drug therapy , Failure to Thrive/drug therapy , Administration, Topical , Abnormalities, Multiple/drug therapy , Nevus, Sebaceous of Jadassohn/drug therapy , Neurocutaneous Syndromes/drug therapy , Neurocutaneous Syndromes/diagnosis , Skin Abnormalities/drug therapy , Antineoplastic Agents/therapeutic use , Eye Abnormalities/drug therapy , Primary Immunodeficiency Diseases/drug therapyABSTRACT
Background: Early childhood intervention is a form of intervention aimed at children to overcome difficulties in different areas of their development after birth. There are multiple early intervention programmes, but only a few studies assess their efficacy using data. Objective: A systematic review and meta-analysis of early intervention programmes was carried out. Method: Inclusion criteria were considered to be empirical studies, with outcome data on children between 0 and 6 years of age with various developmental problems. The review was conducted in nine databases. Results: Of the total number of studies from 2000 to 2021 in English and Spanish, 40 studies were included that looked at the efficacy of the programmes. Of these, 19 used comparisons with a control group, and 13 used single-subject designs, as well as other designs. The programmes were very diverse, mostly based on behavioural procedures, and aimed at promoting the development of specific areas. The quality of the studies is medium-high. The meta-analysis included 18 studies with a mean effect size d = 0.45 (CI = 0.18, 0.67), with high sample heterogeneity and low study selection bias. Conclusions: Early childhood interventions have a medium and positive efficacy on the skills and abilities of children with developmental problems. The limitations of the reviewed studies are discussed, as well as the need for well-defined programmes, long-term measurements, and comparisons of different types of programmes among them. (AU)
Antecedentes: La atención temprana es una forma de intervención dirigida a niños y niñas para intentar superar las dificultades en distintas áreas de su desarrollo tras el nacimiento. Existen múltiples programas, pero pocos estudios comparando con datos su eficacia. Objetivo: Se ha realizado una revisión sistemática y un metaanálisis de los programas de atención temprana. Método: Como criterios de inclusión se consideró que fuesen estudios empíricos con resultados sobre niños con diversos problemas de desarrollo entre 0 y 6 años. La revisión se realizó con nueve bases de datos. Resultados: Del total de estudios desde 2000 a 2021 en español e inglés se incluyeron 40 estudios que permitían ver la eficacia de los programas. De ellos 19 utilizaron comparaciones frente a un grupo control y 13 con diseños de caso único, además de otros diseños. Los programas de atención temprana fueron muy diversos, en su mayoría basados en procedimientos conductuales y dirigidos a impulsar el desarrollo de áreas específicas. La calidad de los estudios es media-alta. En el metaanálisis se incluyeron 18 estudios con un tamaño del efecto medio, d = 0.45 (CI = 0.18, 0.67), con gran heterogeneidad de las muestras y poco sesgo en la selección de estudios. Conclusiones: Los programas de atención temprana presentan una eficacia media y positiva con respecto a las habilidades y capacidades de los niños y niñas con problemas de desarrollo. Se comentan las limitaciones de los estudios revisados y la necesidad utilizar programas bien definidos, mediciones a largo plazo y comparaciones de diversos tipos de programas entre sí. (AU)
Subject(s)
Humans , Male , Female , Infant, Newborn , Infant , Child, Preschool , Child , Early Intervention, Educational/classification , Early Intervention, Educational/trends , Developmental Disabilities , Growth and Development , Failure to Thrive , Learning Disabilities , Autistic Disorder , Down SyndromeABSTRACT
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.
Subject(s)
Malnutrition , Nutritional Status , Child , Humans , Diet, Vegetarian , Diet, Vegan , Dietary Supplements , Failure to Thrive/diagnosisABSTRACT
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.
Subject(s)
Failure to Thrive , Social Work , Infant , Humans , Child , Failure to Thrive/therapy , Failure to Thrive/diagnosis , Failure to Thrive/etiology , Social WorkersABSTRACT
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.
Subject(s)
Enterocolitis, Necrotizing , Enterostomy , Surgical Stomas , Infant, Newborn , Infant , Humans , Retrospective Studies , Failure to Thrive/etiology , Inflammation , Urea , Enterocolitis, Necrotizing/surgeryABSTRACT
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.
Subject(s)
Ectodermal Dysplasia , Epilepsy , Facies , Failure to Thrive , Heart Defects, Congenital , Status Epilepticus , Humans , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies , Status Epilepticus/diagnostic imaging , Status Epilepticus/genetics , NeuroimagingABSTRACT
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.
Subject(s)
Brain Diseases , Epilepsy , Epileptic Syndromes , Movement Disorders , Spasms, Infantile , Status Epilepticus , Female , Humans , Male , Electroencephalography , Epilepsy/diagnosis , Epilepsy/genetics , Failure to Thrive , Muscle Hypotonia/genetics , Protein Serine-Threonine Kinases/genetics , Retrospective Studies , Seizures , Spasm , Spasms, Infantile/diagnosis , Spasms, Infantile/genetics , Vision DisordersABSTRACT
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.
Subject(s)
Hernias, Diaphragmatic, Congenital , Nutritional Requirements , Child , Female , Humans , Infant , Infant, Newborn , Pregnancy , Energy Intake , Failure to Thrive , Retrospective StudiesABSTRACT
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.
Subject(s)
Failure to Thrive , Growth Disorders , Insulin-Like Growth Factor I , Insulin-Like Peptides , Child , Child, Preschool , Female , Humans , Infant , Male , Insulin-Like Growth Factor Binding Protein 3 , Insulin-Like Growth Factor I/deficiency , Insulin-Like Growth Factor I/therapeutic use , Recombinant Proteins/therapeutic use , Siblings , STAT5 Transcription Factor/genetics , SyndromeABSTRACT
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.
Subject(s)
Failure to Thrive , Premature Birth , Child , Female , Humans , Infant, Newborn , Child, Preschool , Infant , Adolescent , Failure to Thrive/epidemiology , Failure to Thrive/etiology , Overweight/complications , Overweight/epidemiology , Obesity/complications , Obesity/epidemiology , Birth Weight , Weight LossABSTRACT
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.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Ectodermal Dysplasia , Epilepsy , Facies , Failure to Thrive , Heart Defects, Congenital , Humans , Prospective Studies , Epilepsy/drug therapy , Epilepsy/genetics , Levetiracetam , Seizures/drug therapy , Seizures/genetics , Anticonvulsants/therapeutic useSubject(s)
Failure to Thrive , Growth Disorders , Infant , Humans , Body Weight , Growth Disorders/diagnosis , Growth Disorders/therapyABSTRACT
Noonan, Costello and Cardio-facio-cutaneous syndromes belong to a group of disorders named RASopathies due to their common pathogenetic origin that lies on the Ras/MAPK signaling pathway. Genetics has eased, at least in part, the distinction of these entities as they are presented with overlapping clinical features which, sometimes, become more pronounced with age. Distinctive face, cardiac and skeletal defects are among the primary abnormalities seen in these patients. Skeletal dysmorphisms range from mild to severe and may include anterior chest wall anomalies, scoliosis, kyphosis, short stature, hand anomalies, muscle weakness, osteopenia or/and osteoporosis. Patients usually have increased serum concentrations of bone resorption markers, while markers of bone formation are within normal range. The causative molecular defects encompass the members of the Ras/MAPK/ERK pathway and the adjacent cascades, important for the maintenance of normal bone homeostasis. It has been suggested that modulation of the expression of specific molecules involved in the processes of bone remodeling may affect the osteogenic fate decision, potentially, bringing out new pharmaceutical targets. Currently, the laboratory imprint of bone metabolism on the clinical picture of the affected individuals is not clear, maybe due to the rarity of these syndromes, the small number of the recruited patients and the methods used for the description of their clinical and biochemical profiles.
Subject(s)
Ectodermal Dysplasia , Heart Defects, Congenital , Humans , ras Proteins/metabolism , Heart Defects, Congenital/genetics , Heart Defects, Congenital/metabolism , Heart Defects, Congenital/pathology , Ectodermal Dysplasia/genetics , Ectodermal Dysplasia/metabolism , Failure to ThriveABSTRACT
Immune checkpoint blockade has become standard treatment for many types of cancer. Such therapy is indicated most often in patients with advanced or metastatic disease but has been increasingly used as adjuvant therapy in those with early-stage disease. Adverse events include immune-related organ inflammation resembling autoimmune diseases. We describe a case of severe immune-related gastroenterocolitis in a 4-month-old infant who presented with intractable diarrhea and failure to thrive after in utero exposure to pembrolizumab. Known causes of the symptoms were ruled out, and the diagnosis of pembrolizumab-induced immune-related gastroenterocolitis was supported by the results of histopathological assays, immunophenotyping, and analysis of the level of antibodies against programmed cell death protein 1 (PD-1). The infant's condition was successfully treated with prednisolone and infliximab.
