Natural history of KBG syndrome in a large European cohort.

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.

Characteristics of Acute Nystagmus in the Pediatric Emergency Department.

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.

Acute ataxia in paediatric emergency departments: a multicentre Italian study.

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.

Vitamin D as a drug.

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.