Short Stature and Distinct Growth Characteristics in Angelman Syndrome.

Objectives - Angelman syndrome (AS) is a rare, genetic, neurodevelopmental disorder characterized by severe impairments in speech, cognition and motor skills accompanied by unique behaviors, distinct facial features and high prevalence of epilepsy and sleep problems. Despite some reports of short stature among AS patients, this feature is not included in the clinical criteria defined in 2005. We investigated growth patterns among AS patients with respect to mutation type, growth periods, family history and endocrine abnormalities. Methods - Data was collected from patients' medical files in AS national clinic. Mutation subtypes were divided to deletion and non-deletion. Four growth periods were defined: preschool, childhood, peak-height velocity, and final-height. Results - The cohort included 88 individuals (46 males), with 54 (61.4%) carrying deletion subtype. A median of 3 observations per individual , produced 280 data points. Final-height-SDS was significantly lower compared to general population (-1.23±1.26, p<0.001), and in deletion group vs. non-deletion (-1.67±1.3 vs. -0.65±0.96, p=0.03). Final-height-SDS was significantly lower compared to height-SDS in preschool period (-1.32 vs -0.47, p=0.007). Patient's final-height-SDS was significantly lower than the parents' (∆final-height-SDS=0.94±0.99, p=0.002). IGF1-SDS was significantly decreased compared to general population (-0.55±1.61, p=0.04), with lower values among deletion group (-0.70±1.44, p=0.01) Conclusions - AS patients demonstrate specific growth pattern with deceleration during childhood and adolescence resulting in significantly decreased final height compared to normal population, and even lower among deletion subgroup, which could be attributed to reduced IGF1 levels. We propose adding short stature to the clinical criteria and developing adjusted growth curves for AS population.

Cerebral and portal vein thrombosis, macrocephaly and atypical absence seizures in Glycosylphosphatidyl inositol deficiency due to a PIGM promoter mutation.

Defects of the glycosylphosphatidylinositol (GPI) biosynthesis pathway constitute an emerging subgroup of congenital disorders of glycosylation with heterogeneous phenotypes. A mutation in the promoter of PIGM, resulting in a syndrome with portal vein thrombosis and persistent absence seizures, was previously described in three patients. We now report four additional patients in two unrelated families, with further clinical, biochemical and molecular delineation of this unique entity. We also describe the first prenatal diagnosis of PIGM deficiency, allowing characterization of the natural history of the disease from birth. The patients described herein expand the phenotypic spectrum of PIGM deficiency to include macrocephaly and infantile-onset cerebrovascular thrombotic events. Finally, we offer insights regarding targeted treatment of this rare disorder with sodium phenylbutyrate.

Triclofos Sodium for Pediatric Sedation in Non-Painful Neurodiagnostic Studies.

AIM: Triclofos sodium (TFS) has been used for many years in children as a sedative for painless medical procedures. It is physiologically and pharmacologically similar to chloral hydrate, which has been censured for use in children with neurocognitive disorders. The aim of this study was to investigate the safety and efficacy of TFS sedation in a pediatric population with a high rate of neurocognitive disability. METHODS: The database of the neurodiagnostic institute of a tertiary academic pediatric medical center was retrospectively reviewed for all children who underwent sedation with TFS in 2014. Data were collected on demographics, comorbidities, neurologic symptoms, sedation-related variables, and outcome. RESULTS: The study population consisted of 869 children (58.2% male) of median age 25 months (range 5-200 months); 364 (41.2%) had neurocognitive diagnoses, mainly seizures/epilepsy, hypotonia, or developmental delay. TFS was used for routine electroencephalography in 486 (53.8%) patients and audiometry in 401 (46.2%). Mean (± SD) dose of TFS was 50.2 ± 4.9 mg/kg. Median time to sedation was 45 min (range 5-245), and median duration of sedation was 35 min (range 5-190). Adequate sedation depth was achieved in 769 cases (88.5%). Rates of sedation-related adverse events were low: apnea, 0; desaturation ≤ 90%, 0.2% (two patients); and emesis, 0.35% (three patients). None of the children had hemodynamic instability or signs of poor perfusion. There was no association between desaturations and the presence of hypotonia or developmental delay. CONCLUSION: TFS, when administered in a controlled and monitored environment, may be safe for use in children, including those with underlying neurocognitive disorders.