Rare familial TSC2 gene mutation associated with atypical phenotype presentation of Tuberous Sclerosis Complex.

Tuberous sclerosis complex (TSC) is a neurocutaneous disorder that results from mutations within either the TSC1 gene or the TSC2 gene. Diagnosis is based on well-established clinical criteria or genetic criteria. We describe an 18-month-old boy who presented with seizures and a single hypopigmented macule. He did not meet consensus criteria for the clinical diagnosis of TSC. Exome sequencing revealed a heterozygous TSC2 mutation (c.5138G>A (p.Arg1713His)) in the patient. This heterozygous alteration was detected in his mother as well as several other maternal family members. The mother and other family members with the mutation were asymptomatic except for the presence of hypopigmented macules. The phenotypic characteristics of the individuals in this family were not suggestive of a TSC2 mutation as none satisfied the clinical criteria for even a diagnosis of possible TSC. This case provides evidence for a unique TSC2 mutation that resulted in an atypical clinical presentation and indicates potential shortcomings of the current diagnostic criteria for TSC. These findings may have implications for genetic counseling and screening. © 2017 Wiley Periodicals, Inc.

Facial Expression in Response to Smell and Taste Stimuli in Small and Appropriate for Gestational Age Newborns.

Small for gestational age newborns can later suffer from eating difficulties and slow growth. Nutritional preferences can be influenced by changes in sensory perception of smell and taste. To determine whether these could be detected at birth, the authors examined the different recognition pattern of smell and taste in small for gestational age newborns compared to appropriate for gestational age controls, as expressed by gusto-facial and naso-facial reflexes. The authors performed video analysis of facial expressions of 10 small for gestational age and 12 control newborns exposed to various tastes and smells. No difference in the facial recognition patterns for taste or smell was demonstrated between small for gestational age and controls, except for perception of distilled water. Newborns show recognizable patterns of facial expression in response to taste and smell stimuli. Perception of taste and smell in small for gestational age newborns is not different from controls, as measured by the method of facial recognition.

Neonatal neuropsychology: emerging relations of neonatal sensory-motor responses to white matter integrity.

The neonatal period is considered to be essential for neurodevelopment and wellbeing throughout the life span, yet little is known about brain-behavior relationships in the neonatal period. The aim of this study was to evaluate the association between neonatal sensory-motor regulation and white-matter (WM) integrity of major fiber tracts in the neonatal period. We hypothesized that WM integrity of sensory-motor systems would predict neurobehavioral maturation during the first month of life. Forty-nine premature neonates underwent magnetic-resonance-imaging at term. Diffusion-tensor-imaging analysis was performed in major WM tracts along with repeated neonatal neurobehavioral evaluations assessing sensory reactivity and motor regulation. Difficulties in one or more behavioral sub-category, mostly in auditory and visual attention, hypotonicity and jitteriness, were documented in 78.3% infants at term. Sixty-six percent of infants experienced difficulties, mostly in auditory attention, head-neck control, hypotonicity and motor asymmetry, at 44 weeks. Attention difficulties were associated with reduced integrity of cerebral and superior cerebellar peduncles; while tonicity was associated with reduced integrity of the corpus-callosum and inferior-posterior tracts. Overall, results showed that early maturing tracts were related with the degree of typicality of sensory reactivity status while late maturing tracts were related with the degree of typicality of tonic regulation. WM integrity and maturation factors explained 40.2% of the variance in neurobehavior at 44 weeks. This study suggests that in preterm neonates, deviant sensory-motor reactivity can be detected very early in development in manners that are related to lower integrity/maturational level of early and late maturing fiber tracts.

Diffuse excessive high signal intensity in low-risk preterm infants at term-equivalent age does not predict outcome at 1 year: a prospective study.

INTRODUCTION: The outcome of premature infants with only diffuse excessive high signal intensity (DEHSI) is not clear. We explored the relationship between DEHSI, white matter (WM) diffusion characteristics, perinatal characteristics, and neurobehavioral outcome at 1 year in a homogenous group of preterm infants without major brain abnormalities. METHODS: Fifty-eight preterm infants, gestational age 29 ± 2.6 weeks, underwent an MRI at term-equivalent age (TEA). Griffiths Mental Developmental Scales, neurological assessment, and Parental Stress Index (PSI) were performed at 1 year corrected age. These measures were compared between preterm infants according to DEHSI classification (none, mild, moderate). Diffusion tensor imaging was used in major WM volumes of interest to objectively measure the degree of WM maturation. RESULTS: No significant differences were detected in the perinatal risk characteristics, neurobehavioral outcome, and PSI at 1 year between infants with different DEHSI classifications. In infants with DEHSI, increased axial and radial diffusivities were detected in the optic radiations, centrum semiovale, and posterior limb of the internal capsule, indicating less advanced maturation of the WM. Significant correlations were detected between the time interval from birth to MRI and the WM microstructure in infants without DEHSI. CONCLUSION: DEHSI in premature infants is neither a predictive measure for short-term adverse neurobehavioral outcome nor related to perinatal risk characteristics. Extrauterine exposure time had a differential effect on WM maturational trajectories in infants with DEHSI compared to those without. We suggest DEHSI may represent an alteration in WM maturational characteristics. Further follow-up studies may verify later consequences of DEHSI in premature infants.

Normal polysomnographic respiratory values in children and adolescents.

STUDY OBJECTIVES: Polysomnography is important in the evaluation of children and adolescents with sleep-disordered breathing. Adult criteria for obstructive sleep apnea have been shown to be inapplicable to children. Nevertheless, very little data are available regarding normal respiratory parameters during sleep in healthy children and adolescents. The purpose of the study was to characterize normal polysomnography values in healthy children and adolescents and to establish respiratory reference values for pediatric polysomnography. DESIGN, SETTING AND PARTICIPANTS: Seventy healthy, normal children and adolescents were studied. Age ranged from 1 to 15 years (mean +/- SD, 8.02 +/- 4.57 years). All children underwent overnight polysomnography including EEG, electromyography, electrooculography, ECG, pulse oximetry arterial oxygen saturation (SpO(2)), chest wall and abdomen motion, oral and nasal airflow, and end-tidal PCO(2) (PETCO(2)). RESULTS: Three children (4%) had a mean of 0.37 obstructive apneas (OAs) per hour of sleep (1 to 5 OAs per child per study), with mean apnea duration of 10.3 +/- 2.1 s. This was not accompanied with oxygen desaturation. Twenty-six children had one to seven central apneas (CAs) per child, resulting in a mean of 0.4 CAs per hour of sleep (median, 0.33; 97.5 percentile, 0.9). Eleven of the 58 events of CA in six children coincided with oxygen desaturation to a minimum of 88% (nadir apnea desaturation range, 88 to 93%). The mean SpO(2) was 97.2 +/- 0.8% with SpO(2) nadir of 94.6 +/- 2.2%. PETCO(2) > 45 mm Hg occurred for 1.6 +/- 3.8% of total sleep time (TST) in 21 of 70 children (30%), with a distribution of 1.3 +/- 3.03% in the range of 46 to 47 mm Hg; < 0.7% were within the range of 48 to 50 mm Hg; and in 0.29 +/- 0.24% of TST, PETCO(2) values were > 50 mm Hg. CONCLUSIONS: Based on these data, the recommended limits for normal values are as follows: OA index, 1; CA index, 0.9; oxygen desaturation, 89%; baseline saturation, 92%; and PETCO(2) > 45 mm Hg for < 10% of TST.