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Succinic semialdehyde dehydrogenase (SSADH) deficiency is an ultra-rare inborn error of metabolism that results in disrupted gamma-amino butyric acid (GABA) catabolism. In addition to developmental delay, intellectual disability, hypotonia, ataxia, and seizures, a variety of neuropsychiatric symptoms may occur, including psychosis. By highlighting all available and relevant case reports/series, this qualitative review seeks to characterize the prevalence, clinical manifestation, pathophysiology, and treatment of psychotic symptoms in this population. Psychosis occurs in a minority of SSADH-deficient individuals, and most commonly presents as auditory or visual hallucinations with an onset in adolescence or young adulthood. Although the pathophysiology underlying the development of psychosis in this context is not fully understood, it likely in part relates to increased GABA and/or gamma hydroxybutyric acid activity. Although antipsychotic medications should be used cautiously in SSADH deficiency, they may be effective at treating emergent psychotic symptoms.

Introduction: Fragmented REM sleep may impede overnight resolution of distress and increase depressive symptoms. Furthermore, both fragmented REM and depressive symptoms may share a common genetic factor. We explored the associations between REM sleep fragmentation, depressive symptoms, and a polygenic risk score (PRS) for depression among adolescents., Methods: About 161 adolescents (mean age 16.9 ± 0.1 years) from a birth cohort underwent a sleep EEG and completed the Beck Depression Inventory-II the same day. We calculated PRSes for depressive symptoms with PRSice 1.25 software using weights from a recent genome-wide association study for dimensions of depressive symptoms (negative emotion, lack of positive emotion and somatic complaints). REM fragmentation in relation to entire REM duration was manually calculated from all REM epochs. REM latency and density were derived using SomnoMedics DOMINO software., Results: PRSes for somatic complaints and lack of positive emotions were associated with higher REM fragmentation percent. A higher level of depressive symptoms was associated with increased percent of REM fragmentation and higher REM density, independently of the genetic risks. Belonging to the highest decile in depressive symptoms was associated with a 2.9- and 7.6-fold risk of belonging to the highest tertile in REM fragmentation and density. In addition, higher PRS for somatic complaints had an independent, additive effect on increased REM fragmentation., Limitation: A single night's sleep EEG was measured, thus the night-to-night stability of the REM fragmentation-depressive symptom link is unclear., Conclusion: Depressive symptoms and genetic risk score for somatic complaints are independently associated with more fragmented REM sleep. This offers new insights on the quality of sleep and its relation to adolescents' mood., (Copyright © 2018. Published by Elsevier B.V.)

Sleep problems are commonly reported in Rett syndrome (RTT); however the electroencephalographic (EEG) biomarkers underlying sleep dysfunction are poorly understood. The aim of this study was to analyze the temporal evolution of quantitative EEG (qEEG) biomarkers in overnight EEGs recorded from girls (2-9 yrs. old) diagnosed with RTT using a non-traditional automated protocol. In this study, EEG spectral analysis identified high delta power cycles representing slow wave sleep (SWS) in 8-9h overnight sleep EEGs from the frontal, central and occipital leads (AP axis), comparing age-matched girls with and without RTT. Automated algorithms quantitated the area under the curve (AUC) within identified SWS cycles for each spectral frequency wave form. Both age-matched RTT and control EEGs showed similar increasing trends for recorded delta wave power in the EEG leads along the antero-posterior (AP). RTT EEGs had significantly fewer numbers of SWS sleep cycles; therefore, the overall time spent in SWS was also significantly lower in RTT. In contrast, the AUC for delta power within each SWS cycle was significantly heightened in RTT and remained heightened over consecutive cycles unlike control EEGs that showed an overnight decrement of delta power in consecutive cycles. Gamma wave power associated with these SWS cycles was similar to controls. However, the negative correlation of gamma power with age (r = -.59; p<0.01) detected in controls (2-5 yrs. vs. 6-9 yrs.) was lost in RTT. Poor % SWS (i.e., time spent in SWS overnight) in RTT was also driven by the younger age-group. Incidence of seizures in RTT was associated with significantly lower number of SWS cycles. Therefore, qEEG biomarkers of SWS in RTT evolved temporally and correlated significantly with clinical severity.

Introduction: The ring chromosome 20 syndrome (r20) is a rare genetic disorder with a late diagnosis., Case Report: A 17 year old boy with drug-resistant epilepsy of 14 years of evolution, which has moderate mental retardation, behavioral alterations and seizures consisting of complex non-convulsive status and generalized seizures during wakefulness, along with more subtle epileptic manifestations during sleep. Karyotype in peripheral blood showed the existence of a ring chromosome 20, whose breakpoints were p13q13.3, presenting a mosaicism 46,XY[23]/46,XY,r(20)(p13q13.3)[25]., Conclusions: The epileptic r20 syndrome seems to have a characteristic electroclinical phenotype and, although not pathognomonic, should be sufficient for all patients who meet a karyotype in peripheral blood, thus avoiding multiple trials with unnecessary drugs and exhaustive studies. In this sense, the study of sleep EEG may be helpful.

We describe two individuals with the same chromosomal aberrations derived from an unbalanced translocation between chromosomes 8p and 9p, who presented with intellectual disabilities, dysmorphic features, and localization-related epilepsy. Several years after the onset of epilepsy, aggravation of widespread epileptic discharges during sleep resulted in the emergence of absence and/or atonic seizures in both patients; one patient additionally presented with psychomotor deterioration. These symptoms completely disappeared after treatment with ethosuximide and benzodiazepines, and marked improvement was observed in electroencephalographic findings. We review the clinical features of der(8)t(8;9) with particular focus on epileptic complications. We conclude that particular types of chromosomal aberrations may have a propensity to develop the condition categorized as electrical status epilepticus in sleep., (Copyright © 2012 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

We report the case of a young girl who presented severe learning disabilities in oral and written language related to a continuous spike-waves during slow sleep (CSWS) syndrome. A sleep EEG recording obtained in her younger brother, who presented a clinical pattern suggesting developmental dysphasia, also showed a CSWS syndrome. These two clinical cases underscore the need to look for this syndrome in the siblings of an affected child when learning difficulties appear in a child who previously had normal psychomotor development.

Mutations responsible for autosomal dominant nocturnal frontal lobe epilepsy have been identified in two members of the neuronal nicotinic acetylcholine receptor gene family: CHRNA4(ENFL1 locus) and CHRNB2 (ENFL3 locus) coding for alpha4 and beta2 subunit, respectively. However, mutations in these genes account for only a minority (less than 10%) of cases. For a third ADNFLE locus (ENFL2) on chromosome 15q24 the gene was not identified. The involvement of the three loci in the pathogenesis of ADNFLE was investigated in 12 unrelated Italian families, selected on the basis of anamnestic and video-polysomnographic data. Compliant family members were typed for polymorphic markers spanning the analyzed chromosome regions. Linkage analyses excluded association of all chromosome regions with ADNFLE in 72% of cases. In two, four and one families it was impossible to ascertain or exclude association with ENFL1, ENFL2, or ENFL3, respectively, however, no mutations have been detected in the nicotinic receptor genes located in these regions. These data strongly suggest that ENFL1, ENFL2 and ENFL3 are minor loci for the disease and point to the existence of at least a fourth locus for ADNFLE.

Purpose: This report delineates the phenotypic features in a cohort of 58 individuals with Smith-Magenis syndrome (SMS) and compares features of patients with the common microdeletion to those of patients with variable sized deletions, and the three previously reported patients who harbor a mutation in RAI1 (retinoic acid induced 1)., Methods: From December 1990 thru September 1999, 58 persons with SMS were enrolled in a 5-day multidisciplinary clinical protocol at the General Clinical Research Center (GCRC), Texas Children's Hospital. Each patient had a cytogenetically evident deletion in 17p11.2., Results: Of the 51 patients in whom the molecular extent of the chromosomal deletion could be delineated by pulsed-field gel electrophoresis (PFGE) and/or fluorescent in situ hybridization (FISH), 39 (approximately 76%) had the common SMS deletion. Smaller or larger deletions were seen in approximately 12% and approximately 10% of patients, respectively, and 1 patient had a complex chromosomal rearrangement including a deletion in 17p11.2. Parent of origin was determined by polymorphic marker analysis in a subset of patients: maternal approximately 43%, paternal approximately 57%. All patients had impaired cognitive and adaptive functioning and had at least one objective measure of sleep disturbance. Other common features (seen in >50% of patients) include short stature, ophthalmological, and otolaryngological anomalies, hearing impairment, abnormal EEG, and scoliosis. Cardiac and renal anomalies were seen in approximately 45% and approximately 19% of patients, respectively. There are no statistically significant differences in the incidence of these abnormalities in patients with the common deletion compared to those patients with smaller or larger sized deletions., Conclusions: Despite a common deletion size in 76% of patients with SMS, the only constant objectively defined features among these patients are sleep disturbances, low adaptive functioning, and mental retardation. There is no pathognomonic clinical feature, no characteristic cardiovascular defect, renal anomaly, otolaryngological or ophthalmic abnormality in SMS.

Recent advances in circadian biology are identifying key genes and the molecular clockworks they command. These biochemical systems provide new tools for evaluating clinically observed, intrinsic circadian rhythm sleep disorders. A striking example was last year's discovery of a point mutation in a human clock gene that produces a sleep phase syndrome. This finding suggested that other intrinsic sleep disorders may have genetic underpinnings, and that less debilitating variations in sleep/wake behavior may be revealed by molecular screening of known clock genes in broader human populations.

To examine the nature of sleep disturbance in patients with a variant form of late infantile neuronal ceroid lipofuscinosis (CLN5), we studied 12 patients (age range 7-32 years). We used a sleep questionnaire to assess sleep and its disturbances quantitatively. To identify the periodicity in the diurnal rest-activity rhythms, the motor activity level was recorded by activity monitors continuously for a 1-week period with concomitant sleep logs. In addition, whole-night polysomnographic recordings were performed. The patients under 20 years of age had an excess of nocturnal sleep (the mean of the usual duration of nighttime sleep was 10.0 hours) and frequent daytime naps. Frequent shifts of the longest sleep period into the daytime hours and fragmented diurnal rest-activity patterns with no distinct rhythm occurred in the older patients. The progressive disease may damage the internal circadian timing system and also impair the ability of patients with variant late infantile neuronal ceroid lipofuscinosis to use external time cues for synchronization of their sleep and environmental time.