Ceroid lipofuscinosis type 2 disease: Effective presymptomatic therapy-Oldest case of a presymptomatic enzyme therapy.

Neuronal ceroid lipofuscinosis type 2 (CLN2) disease is a rare, lysosomal storage disorder that causes pediatric onset neurodegenerative disease. It is characterized by mutations in the TPP1 gene. Symptoms begin between 2 and 4 years of age with loss of previously acquired motor, cognitive, and language abilities. Cerliponase alfa, a recombinant human TPP1 enzyme, is the only approved therapy. We report the first presymptomatic cerliponase alfa intraventricular treatment in a familial case of CLN2 related to a classical TPP1 variant. Sister 1 presented with motor, cognitive, and language decline and progressive myoclonic epilepsy since the age of 3 years, evolved with severe diffuse encephalopathy, received no specific treatment, and died at 11 years. Sister 2 had a CLN2 presymptomatic diagnosis and has been treated with cerliponase since she was 12 months old. She is now 6 years 8 months and has no CLN2 symptom except one generalized seizure 1 year ago. No serious adverse event has occurred. Repeated Wechsler Preschool and Primary Scale of Intelligence, Fourth Edition standardized index scores are heterogeneous in the extremely low to low average ranges. Mean length of utterances, a global index of sentence complexity, showed a delay, but a gradual improvement. The reported case enhances the major contribution of presymptomatic diagnosis and significant middle-term treatment benefit for patients with CLN2.

The longitudinal evolution of cerebral blood flow in children with tuberous sclerosis assessed by arterial spin labeling magnetic resonance imaging may be related to cognitive performance.

OBJECTIVE: To study longitudinal changes in tuber and whole-brain perfusion in children with tuberous sclerosis complex (TSC) using arterial spin labeling (ASL) perfusion MRI and correlate them with pathological EEG slow wave activity and neurodevelopmental outcomes. METHODS: Retrospective longitudinal cohort study of 13 children with TSC, 3 to 6 serial ASL-MRI scans between 2 months and 7 years of age (53 scans in total), and an EEG examination performed within 2 months of the last MRI. Tuber cerebral blood flow (CBF) values were calculated in tuber segmentation masks, and tuber:cortical CBF ratios were used to study tuber perfusion. Logistic regression analysis was performed to identify which initial tuber characteristics (CBF value, volume, location) in the first MRI predicted tubers subsequently associated with EEG slow waves. Whole-brain and lobar CBF values were extracted for all patient scans and age-matched controls. CBF ratios were compared in patients and controls to study longitudinal changes in whole-brain CBF. RESULTS: Perfusion was reduced in tubers associated with EEG slow waves compared with other tubers. Low tuber CBF values around 6 months of age and large tuber volumes were predictive of tubers subsequently associated with EEG slow waves. Patients with severe developmental delay had more severe whole-brain hypoperfusion than those with no/mild delay, which became apparent after 2 years of age and were not associated with a higher tuber load. CONCLUSIONS: Dynamic changes in tuber and brain perfusion occur over time. Perfusion is significantly reduced in tubers associated with EEG slow waves. Whole-brain perfusion is significantly reduced in patients with severe delay. KEY POINTS: • Tubers associated with EEG slow wave activity were significantly more hypoperfused than other tubers, especially after 1 year of age. • Larger and more hypoperfused tubers at 6 months of age were more likely to subsequently be associated with pathological EEG slow wave activity. • Patients with severe developmental delay had more extensive and severe global hypoperfusion than those without developmental delay.

Siblings of children with a complex chronic disorder treated by non-invasive ventilation.

AIM: The aim of the study was to assess the emotional and behavioural functioning of siblings of children treated with long term non-invasive ventilation (NIV). METHODS: Parents of children treated with NIV completed the Child Behaviour Checklist and a qualitative questionnaire for each sibling, aged 1.5-18 years old. RESULTS: The parents of 49 ventilated children were questioned about 79 siblings. For the siblings aged 1.5-5, mean total T score was 57 ± 22 (range 28-92), and five siblings (31%) were in the clinical range. For the siblings aged 6-18, mean total T score was 49 ± 12 (range 26-71), and six siblings (10%) were in the clinical range. Siblings felt responsible for their affected sibling (31%) and involved with his/her illness (52%), with 31% being worried about him/her. A change in behaviour was observed in 19% of the siblings since the initiation of NIV; 26% were impacted by the use of the NIV device. CONCLUSIONS: The majority of siblings of children treated with NIV do not present significant emotional and behavioural problems. They feel deeply responsible for their affected sibling and involved in his/her illness and treatment, highlighting the importance to involve the siblings in the care of the affected child.

Attachment insecurity in infants with infantile spasms: Maternal anxiety and sadness, and infant's temperament outweigh disease severity.

OBJECTIVE: The aim of this study was to investigate attachment behavior in a population of infants with infantile spasms (ISs) using the Strange Situation Procedure (SSP) and to explore factors associated with the infants' attachment behavior. METHODS: The SSP was assessed in a population of 29 children with ISs during the second year of life. In mothers, we assessed anxiety, depression, maternal emotions, and perception of the temperament of the child, and sociodemographic characteristics. In children, we assessed epilepsy characteristics, response to antiepileptic drugs (AEDs) at the time of the SSP, and the child's outcome at 3 years of age, in terms of intellectual disability (ID), and autism spectrum disorder (ASD). RESULTS: Insecure attachment was higher than in the general population (68% versus 32%). It was associated with maternal anxiety, sadness, and maternal representation of the child at 12 months but with none of the child characteristics including ID, ASD, response to AEDs, or ISs etiology. SIGNIFICANCE: Nonspecific dimensions were more important than disease characteristics for the infants' attachment behavior. In conclusion, we propose that interventions targeting mother-child interaction could prevent attachment insecurity and the developmental consequences of early epilepsy.

Drawing of their own sleep by children with sleep-disordered breathing gives insight into their imaginary life.

AIM: To examine how children with sleep-disordered breathing express their own sleep through drawing. METHODS: Children hospitalised for a sleep study in a sleep laboratory of a tertiary hospital were asked to draw a human figure and themselves while asleep. Characteristics of the two drawings were analysed and compared along with a descriptive analysis of some drawings. RESULTS: Children with sleep-disordered breathing and an associated disorder, n = 34, age 5-11 years, participated in the study. The size of the human figure, the colours used, the orientation of the sheet, the type of drawing strokes and the objective quality of the drawing were comparable between the two drawings. On the sleep drawing, 71% of the children drew a bed, 15% drew themselves asleep, 19% represented snoring and 12% night elements. Sixty-two per cent of the children preferred the human drawing to the sleep drawing. A descriptive analysis of 12 drawings showed the influence of the associated disorder on the two drawings. CONCLUSION: This study showed how the associated disease of children with sleep-disordered breathing infiltrated their imaginary life. The sleep drawing gave useful information about representation, fears and wishes in relation to the associated disease and the child's sleeping.

Autism spectrum disorders in propionic acidemia patients.

Propionic acidemia is the result of a deficiency in propionyl-CoA carboxylase activity. Chronic neurologic and cognitive complications frequently occur, but the psychiatric evolution of the disorder is not well documented. We conducted a pedopsychiatric evaluation of 19 children, adolescents and young adults, aged between 2 and 25 years, using ADI-R, CARS-T, as well as ADOS when autism spectrum disorder was suspected. Previous psychometric examinations were also taken into consideration. Thirteen patients had an IQ < 80. Two patients presented with autism and two additional patients with other autism spectrum disorders. Five patients did not fulfill diagnostic criteria for autism spectrum disorder but showed difficulties indicative of a broader autism phenotype (BAP). Four other patients had severe anxiety manifestations related to their disease. Two patients presented with acute psychotic episodes. The number of decompensations in the first 3 years of life was lower in patients with autism spectrum disorder or related symptoms. These patients were also older when they were assessed (median age of 15 years old versus 11 years old). There was no significant correlation between 3-hydroxypropionate levels during the first 6 years of life and autism spectrum disorder diagnosis. In conclusion, autism spectrum disorder is frequent in patients with propionic acidemia. These patients should undergo in-depth psychiatric evaluation and be screened for autism spectrum disorder. Further studies are needed to understand the underlying mechanisms.

Parents of children referred to a sleep laboratory for disordered breathing reported anxiety, daytime sleepiness and poor sleep quality.

AIM: We evaluated the impact that having a child with sleep-disordered breathing had on their parents, including their own sleep quality. METHODS: Questionnaires were completed by 96 parents of 86 children referred for a sleep study or control of continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) at the sleep laboratory of the Necker Hospital, Paris, France, between October 2015 and January 2016. The questionnaires evaluated anxiety and depression, family functioning, the parents' quality of life, daytime sleepiness and sleep quality. RESULTS: The children had a mean age of seven ±five years and most of the responses (79%) came from their mothers. These showed that 26% of parents showed moderate-to-severe anxiety, 8% moderate-to-severe depression, 6% complex family cohesion, 59% moderate-to-severe daytime sleepiness and 54% poor sleep quality. Anxiety was higher in mothers than in fathers (p < 0.001). The questionnaire scores did not differ according to the child's age, the results of the sleep studies or the CPAP or NIV treatment. The symptoms seem to be more commonly related to the child's underlying disease than their sleep-disordered breathing. CONCLUSION: The parents of children referred to a sleep laboratory reported frequent anxiety, daytime sleepiness and poor sleep quality.

Autism spectrum disorder phenotype and intellectual disability in females with epilepsy and PCDH-19 mutations.

INTRODUCTION: Autism features and various degrees of cognitive deficit are reported in patients with PCDH-19 mutations and epilepsy. Autism spectrum disorder (ASD) and, often, cognitive profile are usually assessed clinically. We studied autism phenotype and cognitive outcome in a series of patients using standardized tools for development and ASD. We aimed to describe the phenotype of ASD in this series and to understand whether ASD is strictly linked to intellectual disability (ID) or is present as a comorbidity. METHODS: Eight females aged 5 to 17years old with PCDH-19 mutations and epilepsy were recruited. For ASD diagnosis, the Autism Diagnostic Interview - Revised (ADI-R) and the Autism Diagnosis Observation Schedule (ADOS) were administered. Patients underwent a neuropsychological examination with tests measuring global intellectual efficiency (WPPSI-III and WISC-IV), language, and executive and social cognition abilities. Parental adaptive behavioral questionnaires were also obtained (VABS, CBCL, and BRIEF). RESULTS: Six out of eight patients presented with ASD and ID. Two patients had neither ASD nor ID, and both had the latest age of onset for their epilepsy. All cognitive functions were deficient, but theory-of-mind abilities compared to other cognitive features were even impaired. Features of ASD lacked major repetitive and stereotyped behaviors and show some differences with the classical ASD features related to ID. CONCLUSION: Our results show a large spectrum of ID and a very high rate of ASD in patients with epilepsy and PCDH-19 mutations. Autism spectrum disorder seems to be a genuine comorbidity, more than a consequence of ID. It highlights the importance of standardized psychiatric and cognitive evaluation in order to establish a tailored rehabilitation program.

Infant's engagement and emotion as predictors of autism or intellectual disability in West syndrome.

West syndrome (WS) is a rare epileptic encephalopathy with early onset and a high risk of autistic outcome. The PréAut grid assesses this risk following WS onset by taking into account synchrony and emotion in interactions and by evaluating the baby's active desire to engage in pleasant interactions (especially the infant's early active behaviors that encourage being gazed at or kissed by the mother or to share joy with her). We followed a sample of 25 WS patients prospectively from disease onset and assessed whether the PréAut grid before 9 months, and the checklist for autism in toddlers (CHAT) at 18 and 24 months predicted autism or intellectual disability (ID) outcomes at 4 years. We found that the PréAut grid at 9 months (sensitivity = 0.83; specificity = 1) had similar prediction parameters as the CHAT at 18 months (sensitivity = 0.90; specificity = 0.83) and 24 months (sensitivity = 0.92; specificity = 1). WS patients with a positive PréAut screening at 9 months had a risk of having autism or ID at 4 years, which is 38 times that of children with a negative PréAut grid [OR = 38.6 (95 % CI 2.2-2961); p = 0.006]. We conclude that the PréAut grid could be a useful tool for the early detection of autism or ID risk in the context of WS. Further research is needed to assess the PréAut grid in other contexts (e.g. infants at high-risk for non-syndromic autism).

Current psychopathology models emphasize very early intersubjectivity-based interventions in children to prevent later mental disorders.

Current psychopathology models have evolved toward dimensional models, in which symptoms and diseases are at the extremes of dimensions. Despite these new dimensional proposals, classifications and third-person approach have shown limitations. Their extraordinary evolution nevertheless underlines the contributions of developmental and psychodynamic frameworks. Developmental contributions have made it possible to evolve from disorders centered on a first-person perspective. Complementarily to the first-person/third-person perspectives, we advocate a second-person perspective, based on intersubjectivity. This perspective reverses the intuitive trend to focus our interventions on the most specific symptoms and syndromes, and advocates instead interventions on a "p" general factor that are both generalized and highly targeted. The implications are (1) to intervene as early as possible, (2) to base the definition of our therapeutic targets on an intersubjective perspective, (3) to identify and enhance children's and parents' strengths. These empirically informed directions are not in the current mainstream of psychopathology frameworks, and need to be developed.

Effect of long term noninvasive ventilation in children on parent's quality of life.

OBJECTIVE: Improving or maintaining the quality of life of the family of children treated with long term continuous positive airway pressure (CPAP) or noninvasive ventilation (NIV) is a major concern; but studies are scarce. The aim of the study was to evaluate the impact of long term CPAP or NIV in children on anxiety, depression, quality of sleep, and quality of life of their parents. METHODS: Validated questionnaires evaluating anxiety and depression (hospital anxiety and depression scale), sleep quality (Pittsburgh sleep quality index), daytime sleepiness (Epworth sleepiness scale), and parents' quality of life (PedsQL family impact module) were completed by parents of children who were started on CPAP/NIV before (M0) and after 6-9 months (M6) of treatment. RESULTS: The questionnaires of 36 parents (30 mothers, 6 fathers) of 31 children were analyzed. For the entire group, no significant change was observed in anxiety, depression, sleep quality, daytime sleepiness, and quality of life between M0 and M6. When analyzing questionnaire class changes between M0 and M6: anxiety was relieved in 23% of parents and worsened in 29%, depression was relieved in 14% and worsened in 20%, sleep quality improved in 43% and worsened in 27%, sleepiness improved in 26% and worsened in 17%, with no change in the other parents. CONCLUSION: Long term CPAP/NIV in children had no significant effect on parents' anxiety, depression, sleep quality, and quality of life.

Separation Practices in Children and Adolescents Admitted for Suicidal Behavior: A National Survey of French Psychiatrists.

Objectives: To assess practices of French psychiatrists regarding their management of children and adolescents with suicidal behaviors, focusing on the use of a separation protocol in which the youths are separated from their relatives. Methods: In 2017, we conducted an online cross-sectional survey of French psychiatrists caring for children and adolescents. Participants were asked to describe their practice of a separation protocol in children and adolescents admitted for suicidal behavior. Our main analysis followed a descriptive approach. We also explored whether participant characteristics were associated with the use of a separation protocol. Results: The response rate was 218/2403 (9,1%); 57.9 % of respondents worked in a University hospital, and 60% of respondents reported routinely hospitalizing children. A separation protocol was set up by 91.1% of survey participants (systematically 39.6%, on a case-by-case basis 51.5%). The mean age from which a separation protocol was indicated was above 11 years; 64% of participants reported a separation period of ≤ 48 h. The most common (87%) criterion cited for establishing a separation period was family relationship difficulties. The most common (80.9%) reason to justify the use of a separation protocol was to allow a better clinical assessment. Exploratory analyses did not identify any participant characteristics associated with the use of a separation protocol (p > 0.2 for all). Conclusion: The use of a separation protocol in children and adolescents admitted for suicidal behavior is a widespread practice in France, despite the deprivation of liberty it implies. This raises the question of the relevance and usefulness of such a practice.

Prenatal attachment, anxiety and grief during subsequent pregnancy after medical termination of pregnancy. Attachment to which child?

PURPOSE: To evaluate emotional distress and prenatal attachment throughout a subsequent pregnancy after Termination of Pregnancy (TOP) for fetal abnormality. METHODS: Observational study, in a French Tertiary Maternity. POPULATION: 25 women in a subsequent pregnancy after a medical termination of pregnancy for foetal abnormality, 18-year-old and older. Prenatal Interviews at 20 Gestationnal weeks (GW), 27 GW and 35 GW and Postnatal at 3 months and at each time self-administered questionnaires of anxiety, post-traumatic stress syndrome (PCLS) depressive symptoms (EPDS), prenatal attachment (PAI) and Perinatal Grief Scale (PGS). RESULTS: Pregnancy onset, i.e. before 20 GW, showed increased prevalence of anxiety (16/23, 66.7%), depression (7/23, 30.4%) and post-traumatic stress symptoms (4/16, 25%). Total score on PGS is higher in onset of pregnancy than in the third trimester (p = 0.005). Prenatal attachment was lower during early pregnancy (p = 0.003) and correlated inversely with grief intensity (p = 0.022). During late pregnancy, emotional symptoms decrease, and prenatal attachment stopped increase positively, specifically among women whose foetal abnormality in previous pregnancies were diagnosed late, at an average of 25 GW. CONCLUSION: This research shows the specific dynamics of pregnancies following TOP and highlights the necessity for early prenatal psychological support. One should also pay special attention to prenatal attachment during late pregnancy even after knowing that the fetus is healthy.

Against the odds: psychomotor development of children under 2 years in a Sudanese orphanage.

Providing abandoned children the necessary medical and psychological care as possible after their institutionalization may minimize developmental delays. We describe psychomotor development in infants admitted to an orphanage in Khartoum, Sudan, assessed at admission and over an 18-month follow-up. Psychological state and psychomotor quotients were determined using a simplified Neonatal Behavior Assessment Scale (NBAS), the Brunet-Lezine and Alarm distress baby (ADBB) scale. From May-September 2005, 151 children were evaluated 2, 4, 9, 12 and 18 months after inclusion. At admission, ~15% of children ≤1 month had a regulation impairment according to the NBAS, and 33.8% presented a distress state (ADBB score >5). More than 85% (129/151) recovered normal psychomotor development. The results of the program reinforce the importance of early detection of psychological disorders followed by rapid implementation of psychological case management to improve the development of young children in similar institutions and circumstances.

Association between suicide behaviours in children and adolescents and the COVID-19 lockdown in Paris, France: a retrospective observational study.

This retrospective observational study conducted in Necker Hospital for Sick Children, France (January 2018-June 2020) evaluated a potential temporal association between admissions for suicide behaviours in children and adolescents and the national COVID-19 lockdown (March-May 2020). During the study period, 234 patients were admitted for suicide behaviours (28% male; mean age 13.4 years). Using Poisson regression, we found a significant decrease in the incidence of admissions for suicide behaviour during the lockdown (adjusted incidence rate ratio: 0.46; 95% CI 0.24 to 0.86). This association might result from reduced help-seeking and decreased hospital admission rates during the lockdown, as well as cognitive and environmental factors. Further multicentre studies should be conducted to confirm these findings and investigate whether a compensatory rise in admissions for suicide behaviour occurred in the postlockdown period.

Sleep in preadolescents and adolescents with chronic disorders.

BACKGROUND: The aim of the study was to explore the subjective perception of their own sleep and daytime habits in (pre-)adolescents with chronic diseases. METHODS: Self-administered questionnaires exploring daytime and nighttime habits, health behavior, daytime sleepiness, depression and anxiety were fulfilled by the (pre-)adolescents. RESULTS: Hundred sixty one patients with a chronic disease, aged 14.3±2.6 years old, participated to the study. Mean total time in bed was 8h52±1h09 (range 5h00-11h30) on school days (TIBS) and 9h59±1h28 (range 6h00-14h00) on non school days (TIBN), with 11 (7%) adolescents reporting sleeping ≤7 hours during schooldays. The mean sleep time difference between TIBS and TIBN was 67±95 minutes (range -210-330 min), with 33 patients (20%) having a sleep debt>2h, and 38% reporting sleep initiating problems. Patients with cystic fibrosis had the lowest mean TIBS, the highest percentage (37%) of patients with sleep debt>2h. Obese patients were the sleepiest (33%) with 8% having sleep debt. Anxiety and severe depression were observed in 22% and 20% of the patients, respectively, and correlated with fatigue at wake up and daytime sleepiness. CONCLUSIONS: In these (pre-)adolescents with a chronic disease, 20% had sleep debt but sleep duration was reasonable with acceptable respect of sleep hygiene rules.

The Transgenerational Transmission of Trauma: The Effects of Maternal PTSD in Mother-Infant Interactions.

The objective of the study was to examine the process of mother to infant trauma transmission among traumatized mothers in humanitarian contexts. We investigated the impact of mothers' post-traumatic stress disorder symptoms on the quality of the dyadic interaction by conducting a microanalysis of mother-infant interactions at specific moments when trauma was recalled, compared to more neutral moments. Twenty-four mother-infant dyadic interactions of traumatized mothers and children aged from 1.5 to 30 months Central Africa, Chad, and Cameroon were videotaped during three sequences: a neutral initial session (baseline) exploring mothers' representations of the infant and of their bonding; a second sequence, "the traumatic narration," in which mothers were asked to talk about the difficult events they had experienced; and a third sequence focusing on a neutral subject. Three minutes of each sequence were coded through a specific grid for microanalysis [based on the scales developed at Bobigny Faculty of Medicine and the work of (1)], according to different communication modalities (touch, visual, and vocal), for both the mother and the child. Impact of traumatic event (IES-R), the level of depression and anxiety (HAD) were investigated in order to have a holistic understanding of the trauma transmission mechanism. The data analysis highlighted significant differences in mothers, children and their interaction during the "traumatic narration": mothers touched and looked at the infant less, looked more absent and smiled less, and looked less at the interviewer; infants looked less at the interviewer, and sucked the breast more. The mother-child interaction "infant self-stimulation-mother looks absent" and "Infant sucks the breast-mother looks absent" occurred more often during the mothers' traumatic narrations. The "absence" of the mother during trauma recall seems to have repercussions on infants' behavior and interaction; infants show coping strategies that are discussed. We found no significant associations between interaction and infant gender and age, the severity of traumatic experience, mothers' depression and anxiety symptoms, and the country of residence. The results of the microanalysis of interaction can shed light on the fundamental role of intermodal exchanges between mother and infant in trauma transmission during mothers' trauma reactivation.

Behavior and interaction imaging at 9 months of age predict autism/intellectual disability in high-risk infants with West syndrome.

Automated behavior analysis are promising tools to overcome current assessment limitations in psychiatry. At 9 months of age, we recorded 32 infants with West syndrome (WS) and 19 typically developing (TD) controls during a standardized mother-infant interaction. We computed infant hand movements (HM), speech turn taking of both partners (vocalization, pause, silences, overlap) and motherese. Then, we assessed whether multimodal social signals and interactional synchrony at 9 months could predict outcomes (autism spectrum disorder (ASD) and intellectual disability (ID)) of infants with WS at 4 years. At follow-up, 10 infants developed ASD/ID (WS+). The best machine learning reached 76.47% accuracy classifying WS vs. TD and 81.25% accuracy classifying WS+ vs. WS-. The 10 best features to distinguish WS+ and WS- included a combination of infant vocalizations and HM features combined with synchrony vocalization features. These data indicate that behavioral and interaction imaging was able to predict ASD/ID in high-risk children with WS.

Diagnosis and phenotypic assessment of trimethylaminuria, and its treatment with riboflavin: 1H NMR spectroscopy and genetic testing.

BACKGROUND: Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). The diagnosis of TMAU is challenging because this disorder is situated at the boundary between biochemistry and psychiatry. Here, we used nuclear magnetic resonance spectroscopy to assess TMAU in 13 patients. We also sequenced the FMO3 gene in 11 of these patients. Treatment with vitamin B2 was prescribed. RESULTS: Two patients (aged 3 and 9 years at the initial consultation) had a particularly unpleasant body odor, as assessed by their parents and the attending physicians. The presence of high urine TMA levels confirmed the presence of a metabolic disorder. The two (unrelated) children carried compound heterozygous variants in the FMO3 gene. In both cases, vitamin B2 administration decreased TMA excretion and reduced body odor. The 11 adults complained of an unpleasant body odor, but the physicians did not confirm this. In all adult patients, the urine TMA level was within the normal range reported for control (non-affected) subjects, although two of the patients displayed an abnormally high proportion of oxidized TMA. Seven of the 9 tested adult patients had a hypomorphic variant of the FMO3 gene; the variant was found in the homozygous state, in the heterozygous state or combined with another hypomorphic variant. All 11 adults presented a particular psychological or psychiatric phenotype, with a subjective perception of unpleasant odor. CONCLUSIONS: The results present the clinical and biochemical data of patients complaining of unpleasant body odor. Contrary to adult patients, the two children exhibited all criteria of recessively inherited trimethylaminuria, suspected by parents in infancy. B2 vitamin treatment dramatically improved the unpleasant body odor and the ratio of TMA/Cr vs TMAO/Cr in the urine in the children. Other patients presented a particular psychological or psychiatric phenotype.

Autism spectrum disorder and cognitive profile in children with Dravet syndrome: Delineation of a specific phenotype.

OBJECTIVE: We aimed to assess a cohort of young patients with Dravet syndrome (DS) for intellectual disability (ID) and autism spectrum disorder (ASD) using standardized tools and parental questionnaires to delineate their specific profiles. METHODS: We included 35 patients with DS aged 24 months to 7 years, excluding patients with a developmental age (DA) <18 months (n = 5). We performed specific tests adapted for ID (Psychoeducational Profile, Third Edition [PEP-3]), in addition to the Child Development Inventory (CDI) and Vineland Adaptive Behavior Scales, Second Edition (VABS-II) questionnaires. We used 2 standardized tools for ASD: the Autism Diagnostic Observation Schedule, Second Edition (ADOS-2) and the Autism Diagnostic Interview-Revised (ADI-R). We compared the with parental questionnaires and the VABS-II, and with ASD characteristics. RESULTS: PEP-3 subscales showed pathologic development in all but one patient (97%): ID in 23 of 30 (77%), and borderline cognitive functioning in 6 of 30 (22%). Eleven patients (39%) had ASD and 2 (7%) had a Social Communication Disorder (SCD) diagnosis. We found no difference between PEP-3 and CDI categorization except for fine motor skills. We found significant negative correlations between ADOS-2 and PEP-3 for the majority of scores. For patients aged older than 50 months, 2 groups emerged (ASD/no ASD) with significant difference in DA. The logistic regression for ASD diagnosis explained by VABS-II showed a significant effect for Socialization, Motor Skills, and Adaptive Behavior. SIGNIFICANCE: We found a high prevalence of ID in patients with DS. ID is characterized by expressive and comprehensive communication deficits in addition to visuospatial difficulties. ASD showed a specific profile with a relative preservation of social skills, emphasizing a possible underdiagnosis. Parental questionnaires can provide a good assessment of cognitive profile and might allow the difficulty of addressing cognitive scales in DS to be overcome. The profile of ID and ASD should help to establish early adapted rehabilitation programs and emphasizes the global need for care beyond seizures in DS and other developmental epileptic encephalopathies.