Response to Melatonin Treatment in Children With Autism spectrum Disorder and Relationship to Sleep Parameters and Melatonin Levels.

Melatonin is one of the most used pharmacologic treatments for sleep problems in autism spectrum disorder, though its relationship with circadian and sleep parameters is still not well stablished. A naturalistic study was conducted in children with autism spectrum disorder, previously drug-naïve, before and after treatment with immediate-release melatonin. Circadian rhythms and sleep parameters were studied using an ambulatory circadian-monitoring device, and saliva samples were collected enabling determination of dim light melatonin onset. Twenty-six children with autism spectrum disorder (age 10.50 ± 2.91) were included. Immediate-release melatonin modified circadian rhythm as indicated by wrist skin temperature, showing an increase at night. A positive correlation was found between time of peak melatonin and sleep efficiency improvement values. Sleep-onset latency and efficiency improved with immediate-release melatonin. Immediate-release melatonin could be an effective treatment to improve sleep onset and restore a typical pattern of wrist temperature, which appears to be lost in autism spectrum disorder.

Sleep Problems, Circadian Rhythms, and Their Relation to Behavioral Difficulties in Children and Adolescents with Autism Spectrum Disorder.

This was an exploratory cross-sectional study comparing 45 children with ASD to 24 typically developing drug-naïve controls, group-matched on age, sex, and body mass index. Objective data was obtained using the following: an ambulatory circadian monitoring device; saliva samples to determine dim light melatonin onset (DLMO): and three parent-completed measures: the Child Behavior Checklist (CBCL); the Repetitive Behavior Scale-Revised (RBS-R); and the General Health Questionnaire (GHQ28). The CBCL and RBS-R scales showed the highest scores amongst poor sleepers with ASD. Sleep fragmentation was associated with somatic complaints and self-injury, leading to a higher impact on family life. Sleep onset difficulties were associated with withdrawal, anxiety, and depression. Those with phase advanced DLMO had lower scores for "somatic complaints"; "anxious/depressed" state; and "social problems", suggesting that this phenomenon has a protective role.

Clinical description, molecular delineation and genotype-phenotype correlation in 340 patients with KBG syndrome: addition of 67 new patients.

BACKGROUND: KBG syndrome is a highly variable neurodevelopmental disorder and clinical diagnostic criteria have changed as new patients have been reported. Both loss-of-function sequence variants and large deletions (copy number variations, CNVs) involving ANKRD11 cause KBG syndrome, but no genotype-phenotype correlation has been reported. METHODS: 67 patients with KBG syndrome were assessed using a custom phenotypical questionnaire. Manifestations present in >50% of the patients and a 'phenotypical score' were used to perform a genotype-phenotype correlation in 340 patients from our cohort and the literature. RESULTS: Neurodevelopmental delay, macrodontia, triangular face, characteristic ears, nose and eyebrows were the most prevalentf (eatures. 82.8% of the patients had at least one of seven main comorbidities: hearing loss and/or otitis media, visual problems, cryptorchidism, cardiopathy, feeding difficulties and/or seizures. Associations found included a higher phenotypical score in patients with sequence variants compared with CNVs and a higher frequency of triangular face (71.1% vs 42.5% in CNVs). Short stature was more frequent in patients with exon 9 variants (62.5% inside vs 27.8% outside exon 9), and the prevalence of intellectual disability/attention deficit hyperactivity disorder/autism spectrum disorder was lower in patients with the c.1903_1907del variant (70.4% vs 89.4% other variants). Presence of macrodontia and comorbidities were associated with larger deletion sizes and hand anomalies with smaller deletions. CONCLUSION: We present a detailed phenotypical description of KBG syndrome in the largest series reported to date of 67 patients, provide evidence of a genotype-phenotype correlation between some KBG features and specific ANKRD11 variants in 340 patients, and propose updated clinical diagnostic criteria based on our findings.

Desensibilización con Ketocal® en lactante con dieta cetogénica y alergia a proteínas de leche de vaca / Oral desensitization with Ketocal® in an infant with ketogenic diet and cow's milk protein allergy

Introducción: la dieta cetogénica es un tratamiento con eficacia demostrada en la epilepsia infantil refractaria a fármacos. La alergia a la proteína de leche de vaca puede ser una limitación para tratar a lactantes con dieta cetogénica, ya que necesitan un producto que contiene proteínas de leche de vaca (Ketocal®). Caso clínico: presentamos el caso de un lactante con una encefalopatía epiléptica refractaria a fármacos y alergia a las proteínas de leche de vaca IgE mediada al que se quiere instaurar una dieta cetogénica clásica. Se consigue la desensibilización con Ketocal 3:1®, pudiendo utilizarlo en la dieta y logrando una mejoría clínica con el control de las crisis. Discusión: un paciente con epilepsia y alergia a las proteínas de leche de vaca puede beneficiarse de la dieta cetogénica, ya que es posible realizar una inmunoterapia oral con Ketocal® y conseguir, además, una probable resolución de su alergia. (AU)

Introduction: ketogenic diet is a treatment with proven efficacy in drug-refractory childhood epilepsy. Cow's milk protein allergy may be a limitation for treating infants with ketogenic diet, as they need a product that contains cow's milk protein (Ketocal®). Case report: we report the case of an infant with a drug-refractory epileptic encephalopathy and IgE-mediated cow's milk protein allergy, who started a classic ketogenic diet. Oral desensitization was achieved with Ketocal 3:1®, allowing its use in the diet and achieving a clinical improvement with seizure control. Discussion: a patient with epilepsy and cow's milk protein allergy can benefit from the ketogenic diet, since it is possible to perform an oral immunotherapy with Ketocal®, also achieving a probable resolution of his/her allergy. (AU)

[Oral desensitization with Ketocal® in an infant with ketogenic diet and cow's milk protein allergy]. / Desensibilización con Ketocal® en lactante con dieta cetogénica y alergia a proteínas de leche de vaca.

Introduction: Introduction: ketogenic diet is a treatment with proven efficacy in drug-refractory childhood epilepsy. Cow's milk protein allergy may be a limitation for treating infants with ketogenic diet, as they need a product that contains cow's milk protein (Ketocal®). Case report: we report the case of an infant with a drug-refractory epileptic encephalopathy and IgE-mediated cow's milk protein allergy, who started a classic ketogenic diet. Oral desensitization was achieved with Ketocal 3:1®, allowing its use in the diet and achieving a clinical improvement with seizure control. Discussion: a patient with epilepsy and cow's milk protein allergy can benefit from the ketogenic diet, since it is possible to perform an oral immunotherapy with Ketocal®, also achieving a probable resolution of his/her allergy.

Introducción: Introducción: la dieta cetogénica es un tratamiento con eficacia demostrada en la epilepsia infantil refractaria a fármacos. La alergia a la proteína de leche de vaca puede ser una limitación para tratar a lactantes con dieta cetogénica, ya que necesitan un producto que contiene proteínas de leche de vaca (Ketocal®). Caso clínico: presentamos el caso de un lactante con una encefalopatía epiléptica refractaria a fármacos y alergia a las proteínas de leche de vaca IgE mediada al que se quiere instaurar una dieta cetogénica clásica. Se consigue la desensibilización con Ketocal 3:1®, pudiendo utilizarlo en la dieta y logrando una mejoría clínica con el control de las crisis. Discusión: un paciente con epilepsia y alergia a las proteínas de leche de vaca puede beneficiarse de la dieta cetogénica, ya que es posible realizar una inmunoterapia oral con Ketocal® y conseguir, además, una probable resolución de su alergia.

Attention Deficit Hyperactivity and Autism Spectrum Disorders as the Core Symptoms of AUTS2 Syndrome: Description of Five New Patients and Update of the Frequency of Manifestations and Genotype-Phenotype Correlation.

Haploinsufficiency of AUTS2 has been associated with a syndromic form of neurodevelopmental delay characterized by intellectual disability, autistic features, and microcephaly, also known as AUTS2 syndrome. While the phenotype associated with large deletions and duplications of AUTS2 is well established, clinical features of patients harboring AUTS2 sequence variants have not been extensively described. In this study, we describe the phenotype of five new patients with AUTS2 pathogenic variants, three of them harboring loss-of-function sequence variants. The phenotype of the patients was characterized by attention deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD) or autistic features and mild global developmental delay (GDD) or intellectual disability (ID), all in 4/5 patients (80%), a frequency higher than previously reported for ADHD and autistic features. Microcephaly and short stature were found in 60% of the patients; and feeding difficulties, generalized hypotonia, and ptosis, were each found in 40%. We also provide the aggregated frequency of the 32 items included in the AUTS2 syndrome severity score (ASSS) in patients currently reported in the literature. The main characteristics of the syndrome are GDD/ID in 98% of patients, microcephaly in 65%, feeding difficulties in 62%, ADHD or hyperactivity in 54%, and autistic traits in 52%. Finally, using the location of 31 variants from the literature together with variants from the five patients, we found significantly higher ASSS values in patients with pathogenic variants affecting the 3' end of the gene, confirming the genotype-phenotype correlation initially described.

¿Espasmo del sollozo prolongado o crisis epiléptica?: descripción de tres niñas con crisis epilépticas desencadenadas por anoxia / Breath-holding spell or epileptic seizure? A description of three girls with epileptic seizures triggered by anoxia

No disponible

Glut1 deficiency is a rare but treatable cause of childhood absence epilepsy with atypical features.

Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare genetic disorder caused by pathogenic variants in SLC2A1, resulting in impaired glucose uptake through the blood-brain barrier. Our objective is to analyze the frequency of GLUT1-DS in patients with absences with atypical features. Sequencing analysis and detection of copy number variation of the SLC2A1 gene was carried out in patients with atypical absences including: early-onset absence, intellectual disability, additional seizure types, refractory epilepsy, associated movement disorders, as well as those who have first-degree relatives with absence epilepsy or atypical EEG ictal discharges. Of the 43 patients analyzed, pathogenic variations were found in 2 (4.6%). Six atypical characteristics were found in these 2 patients. The greater the number of atypical characteristics presenting in patients with absence seizures, the more likely they have a SLC2A1 mutation. Although GLUT1-DS is an infrequent cause of absence epilepsy, recognizing this disorder is important, since initiation of a ketogenic diet can reduce the frequency of seizures, the severity of the movement disorder, and also improve the quality of life of the patients and their families.

¿Caminan de manera diferente los niños con trastorno por déficit de atención hiperactividad (TDAH)? Relación entre marcha de puntillas idiopática y TDAH / Do children with attention deficit and hyperactivity disorder (ADHD) have a diferent gait pattern? Relationship between idiopathic toe-walking and ADHD

INTRODUCCIÓN: La marcha de puntillas idiopática (MPI) se describe como el patrón de marcha sin apoyo del talón en niños mayores de 3 años. El diagnóstico es clínico y obliga a descartar otras enfermedades neurológicas y traumatológicas-ortopédicas. Se postula su relación con una disfunción vestibular o de sensibilidad propioceptiva. Los niños con trastornos del neurodesarrollo (trastorno del espectro autista, trastorno del lenguaje y cognitivo) presentan frecuentemente MPI. OBJETIVOS: Analizar la frecuencia de MPI en niños con trastorno por déficit de atención e hiperactividad (TDAH). Pacientes y método: Estudio en niños diagnosticados de TDAH con exploración neurológica normal, sin alteraciones en neuroimagen ni trastorno cognitivo o trastorno del espectro autista. Se realizó anamnesis completa y se valoró la presencia de acortamiento aquíleo con goniómetro. RESULTADOS: Se analizó a 312 niños con edad media de 11 años, el 73,7% varones. El subtipo combinado fue el más frecuente (53,8%), seguido del inatento (44,9%) e hiperactivo (1,3%). Un 20,8% de los pacientes presentaban MPI, que era más frecuente en el subtipo combinado (p = 0,054). Solo 32 de estos (49,2%) presentaban acortamiento aquíleo. La presencia de MPI se relacionó con alteraciones en el área de la sociabilidad (p = 0,01), ausencia de dolor en miembros inferiores (p = 0,022) y antecedentes familiares de MPI (p = 0,004). Solo el 11% habían consultado por este motivo previamente. CONCLUSIONES: Al igual que en otros trastornos del neurodesarrollo, los niños con TDAH presentan con mayor frecuencia MPI y acortamiento aquíleo, especialmente entre aquellos con trastornos de comunicación social o antecedentes familiares de MPI. Es fundamental una identificación precoz para instaurar tratamientos eficaces

INTRODUCTION: Idiopathic toe-walking (ITW) is described as a gait pattern with no contact between the heels and the ground in children older than 3 years. The diagnosis is clinical, making it necessary to rule out other neurological and orthopaedic conditions. A relationship between ITW and vestibular dysfunction and/or proprioceptive sensibility has been proposed. Children with neurodevelopmental disorders (autism, language and cognitive disorders) often have ITW. OBJECTIVES: To determine the frequency of ITW in children with attention deficit disorder and hyperactivity (ADHD). PATIENTS AND METHOD: A study was conducted on children diagnosed with ADHD, with normal neurological examination, with no alterations in MRI scan, cognitive disorder or autism. A complete clinical anamnesis was performed and Achilles shortening was measured with a goniometer. RESULTS: The study included 312 children with a mean age of 11 years (73.7% boys). The ADHD combined subtype was the most frequent (53.8%), followed by the inattentive (44.9%), and hyperactive (1.3%). ITW was observed in 20.8% of patients, particularly in the combined subtype (P=.054). Only 32 of them (49.2%) had Achilles shortening. ITW was associated with sociability disorders (P=.01), absence of pain in legs (P=.022), and family history of ITW (P=.004). Only 11% had previously visited a doctor for this reason. CONCLUSIONS: As in other neurodevelopmental disorders, children with ADHD have frequently more ITW and Achilles shortening than controls, especially if they presented with a social communication disorder or a family history of ITW. An early diagnosis is essential to establish effective treatments

[Do children with attention deficit and hyperactivity disorder (ADHD) have a diferent gait pattern? Relationship between idiopathic toe-walking and ADHD]. / ¿Caminan de manera diferente los niños con trastorno por déficit de atención hiperactividad (TDAH)? Relación entre marcha de puntillas idiopática y TDAH.

INTRODUCTION: Idiopathic toe-walking (ITW) is described as a gait pattern with no contact between the heels and the ground in children older than 3years. The diagnosis is clinical, making it necessary to rule out other neurological and orthopaedic conditions. A relationship between ITW and vestibular dysfunction and/or proprioceptive sensibility has been proposed. Children with neurodevelopmental disorders (autism, language and cognitive disorders) often have ITW. OBJECTIVES: To determine the frequency of ITW in children with attention deficit disorder and hyperactivity (ADHD). PATIENTS AND METHOD: A study was conducted on children diagnosed with ADHD, with normal neurological examination, with no alterations in MRI scan, cognitive disorder or autism. A complete clinical anamnesis was performed and Achilles shortening was measured with a goniometer. RESULTS: The study included 312 children with a mean age of 11 years (73.7% boys). The ADHD combined subtype was the most frequent (53.8%), followed by the inattentive (44.9%), and hyperactive (1.3%). ITW was observed in 20.8% of patients, particularly in the combined subtype (P=.054). Only 32 of them (49.2%) had Achilles shortening. ITW was associated with sociability disorders (P=.01), absence of pain in legs (P=.022), and family history of ITW (P=.004). Only 11% had previously visited a doctor for this reason. CONCLUSIONS: As in other neurodevelopmental disorders, children with ADHD have frequently more ITW and Achilles shortening than controls, especially if they presented with a social communication disorder or a family history of ITW. An early diagnosis is essential to establish effective treatments.