RESUMEN
KBG syndrome (KBGS) is characterized by distinctive facial gestalt, short stature and variable clinical findings. With ageing, some features become more recognizable, allowing a differential diagnosis. We aimed to better characterize natural history of KBGS. In the context of a European collaborative study, we collected the largest cohort of KBGS patients (49). A combined array- based Comparative Genomic Hybridization and next generation sequencing (NGS) approach investigated both genomic Copy Number Variants and SNVs. Intellectual disability (ID) (82%) ranged from mild to moderate with severe ID identified in two patients. Epilepsy was present in 26.5%. Short stature was consistent over time, while occipitofrontal circumference (median value: -0.88 SD at birth) normalized over years. Cerebral anomalies, were identified in 56% of patients and thus represented the second most relevant clinical feature reinforcing clinical suspicion in the paediatric age when short stature and vertebral/dental anomalies are vague. Macrodontia, oligodontia and dental agenesis (53%) were almost as frequent as skeletal anomalies, such as brachydactyly, short fifth finger, fifth finger clinodactyly, pectus excavatum/carinatum, delayed bone age. In 28.5% of individuals, prenatal ultrasound anomalies were reported. Except for three splicing variants, leading to a premature termination, variants were almost all frameshift. Our results, broadening the spectrum of KBGS phenotype progression, provide useful tools to facilitate differential diagnosis and improve clinical management. We suggest to consider a wider range of dental anomalies before excluding diagnosis and to perform a careful odontoiatric/ear-nose-throat (ENT) evaluation in order to look for even submucosal palate cleft given the high percentage of palate abnormalities. NGS approaches, following evidence of antenatal ultrasound anomalies, should include ANKRD11.
Asunto(s)
Anomalías Múltiples , Enfermedades del Desarrollo Óseo , Enanismo , Discapacidad Intelectual , Anomalías Dentarias , Embarazo , Femenino , Humanos , Facies , Anomalías Dentarias/genética , Enfermedades del Desarrollo Óseo/genética , Anomalías Múltiples/genética , Anomalías Múltiples/diagnóstico , Discapacidad Intelectual/genética , Discapacidad Intelectual/diagnóstico , Hibridación Genómica Comparativa , Proteínas Represoras/genética , Fenotipo , Enanismo/genética , Pueblo EuropeoRESUMEN
OBJECTIVES: Acute nystagmus (AN) is an uncommon neurologic sign in children presenting to pediatric emergency departments. We described the epidemiology, clinical features, and underlying causes of AN in a large cohort of children, aiming at identifying features associated with higher risk of severe underlying urgent conditions (UCs). METHODS: Clinical records of all patients aged 0 to 18 years presenting for AN to the pediatric emergency departments of 9 Italian hospitals in an 8-year period were retrospectively reviewed. Clinical and demographic features and the underlying causes were analyzed. A logistic regression model was applied to detect predictive variables associated with a higher risk of UCs. RESULTS: A total of 206 patients with AN were included (male-to-female ratio: 1.01; mean age: 8 years 11 months). The most frequently associated symptoms were headache (43.2%) and vertigo (42.2%). Ataxia (17.5%) and strabismus (13.1%) were the most common neurologic signs. Migraine (25.7%) and vestibular disorders (14.1%) were the most common causes of AN. Idiopathic infantile nystagmus was the most common cause in infants <1 year of age. UCs accounted for 18.9% of all cases, mostly represented by brain tumors (8.3%). Accordant with the logistic model, cranial nerve deficits, ataxia, or strabismus were strongly associated with an underlying UC. Presence of vertigo or attribution of a nonurgent triage code was associated with a reduced risk of UCs. CONCLUSIONS: AN should be considered an alarming finding in children given the risk of severe UCs. Cranial nerve palsy, ataxia, and strabismus should be considered red flags during the assessment of a child with AN.
Asunto(s)
Nistagmo Patológico/etiología , Ataxia/complicaciones , Ataxia/diagnóstico , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/diagnóstico , Infecciones del Sistema Nervioso Central/complicaciones , Infecciones del Sistema Nervioso Central/diagnóstico , Niño , Preescolar , Estudios de Cohortes , Enfermedades de los Nervios Craneales/complicaciones , Enfermedades de los Nervios Craneales/diagnóstico , Enfermedades Desmielinizantes/complicaciones , Enfermedades Desmielinizantes/diagnóstico , Mareo/etiología , Servicio de Urgencia en Hospital , Femenino , Cefalea/etiología , Humanos , Hipertensión Intracraneal/complicaciones , Hipertensión Intracraneal/diagnóstico , Italia , Masculino , Trastornos Migrañosos/complicaciones , Trastornos Migrañosos/diagnóstico , Náusea/etiología , Intoxicación/complicaciones , Intoxicación/diagnóstico , Estudios Retrospectivos , Estrabismo/etiología , Vértigo/etiología , Enfermedades Vestibulares/complicaciones , Enfermedades Vestibulares/diagnóstico , Vómitos/etiologíaRESUMEN
OBJECTIVES: To evaluate the causes and management of acute ataxia (AA) in the paediatric emergency setting and to identify clinical features predictive of an underlying clinically urgent neurological pathology (CUNP). STUDY DESIGN: This is a retrospective medical chart analysis of children (1-18 years) attending to 11 paediatric emergency departments (EDs) for AA in an 8-year period. A logistic regression model was applied to identify clinical risk factors for CUNP. RESULTS: 509 patients (mean age 5.8 years) were included (0.021% of all ED attendances). The most common cause of AA was acute postinfectious cerebellar ataxia (APCA, 33.6%). Brain tumours were the second most common cause (11.2%), followed by migraine-related disorders (9%). Nine out of the 14 variables tested showed an OR >1. Among them, meningeal and focal neurological signs, hyporeflexia and ophthalmoplegia were significantly associated with a higher risk of CUNP (OR=3-7.7, p<0.05). Similarly, the odds of an underlying CUNP were increased by 51% by each day from onset of ataxia (OR=1.5, CI 1.1 to 1.2). Conversely, a history of varicella-zoster virus infection and vertigo resulted in a significantly lower risk of CUNP (OR=0.1 and OR=0.5, respectively; p<0.05). CONCLUSIONS: The most frequent cause of AA is APCA, but CUNPs account for over a third of cases. Focal and meningeal signs, hyporeflexia and ophthalmoplegia, as well as longer duration of symptoms, are the most consistent 'red flags' of a severe underlying pathology. Other features with less robust association with CUNP, such as seizures or consciousness impairment, should be seriously taken into account during AA evaluation.
Asunto(s)
Ataxia/epidemiología , Servicio de Urgencia en Hospital/estadística & datos numéricos , Adolescente , Ataxia/etiología , Niño , Servicios de Salud del Niño , Preescolar , Estudios de Cohortes , Femenino , Humanos , Lactante , Italia/epidemiología , Modelos Logísticos , Masculino , Registros Médicos , Estudios RetrospectivosRESUMEN
BACKGROUND: Early-onset neonatal sepsis (EOS) is a serious and potentially life-threatening disease in newborns. C reactive protein (CRP) is the most used laboratory biomarker for the detection of EOS. Little is known about normal reference values of CRP during the perinatal period as several factors are able to influence it. OBJECTIVES: To identify an appropriate range of CRP values in healthy term newborns during the first 48 hours of life. DESIGN: CRP determination was performed in 859 term newborns at 12, 24 and 48 hours of life. Mode of delivery, maternal vaginal culture results, intrapartum antimicrobial prophylaxis (IAP) and other perinatal variables were recorded. RESULTS: CRP mean values were significantly higher at 48 hours (4.10 mg/L) than at both 24 (2.30 mg/L) and 12 hours of life (0.80 mg/L). CRP levels were affected by a number of perinatal proinflammatory variables. In particular, CRP mean values were significantly higher in babies born by vaginal delivery (3.80 mg/L) and emergency caesarean section (3.60 mg/L) than in babies born by elective caesarean section (2.10 mg/L). Completed course of IAP led to lower CRP mean values (2.90 mg/L) than IAP not completed (3.80 mg/L) or not performed (4.70 mg/L). CONCLUSIONS: Postnatal age and mode of delivery significantly influence CRP values. Reliable reference values are crucial in order to obtain an adequate diagnostic accuracy.
Asunto(s)
Proteína C-Reactiva/análisis , Parto Obstétrico/métodos , Profilaxis Antibiótica/métodos , Biomarcadores , Femenino , Humanos , Recién Nacido , Estudios Prospectivos , Valores de Referencia , Vagina/microbiologíaRESUMEN
OBJECTIVES: This study aims to determine whether or not treatment of preterm neonates with PDA using IV ibuprofen can impair renal function and in what range of birth weights and gestational ages the risk of major renal side-effects due to ibuprofen is highest. METHODS: 134 preterm newborns with PDA were enrolled and randomized to receive either placebo or a 3-day-course (10, 5 and 5 mg/kg) of IV ibuprofen. 67 newborns (mGA: 27(+3) w and mBW: 989 g) with PDA received ibuprofen. RESULTS: Subdividing the infants according to BW and to GA, the values of creatinine and BUN were only significantly higher than initial values at the end of the therapy in newborns with a BW ≤1000 g and/or GA ≤26 weeks. Renal impairment is greater the lower the weight and gestational age of the infant at birth. CONCLUSIONS: Ibuprofen significantly impairs renal function in preterm infants with a GA ≤26 weeks and/or in ELBW neonates, while it may be considered safe for infants with a BW >1000 g and/or GA >26 weeks. Thus, before starting therapy with IV ibuprofen, it is essential to take into account the BW and GA of newborns and the effective need for treatment from the point of view of the ratio of risks to benefits, due to its substantial renal side-effects.
Asunto(s)
Conducto Arterioso Permeable/tratamiento farmacológico , Ibuprofeno/efectos adversos , Recien Nacido con Peso al Nacer Extremadamente Bajo , Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Enfermedades Renales/inducido químicamente , Peso al Nacer , Nitrógeno de la Urea Sanguínea , Creatinina/sangre , Inhibidores de la Ciclooxigenasa , Femenino , Edad Gestacional , Tasa de Filtración Glomerular , Humanos , Ibuprofeno/administración & dosificación , Ibuprofeno/uso terapéutico , Recién Nacido , Enfermedades del Prematuro/inducido químicamente , Enfermedades del Prematuro/tratamiento farmacológico , Masculino , Placebos , Factores de RiesgoRESUMEN
Vitamin D has an important role in bone-metabolism (and its deficiency can cause preterm osteopenia, craniotabe and rickets), but it has also non-calcitropic functions. In fact, vitamin D deficiency is correlated to chronic kidney disease, respiratory infections, type 1 diabetes, psoriasis, Crohn disease and neonatal hypocalcemia. Because of the vitamin D deficiency is a global problem, its role as a drug is fundamental for the human health in all ages.