Subjective sleep assessment in individuals with SYNGAP1-associated syndrome.

STUDY OBJECTIVES: Sleep disturbances are common in neurodevelopmental disorders (NDDs), affecting patients and caregivers' quality of life. SYNGAP1-associated syndrome, a rare NDD, is marked by intellectual disability, developmental delay, epilepsy, and sleep issues. However, research on sleep quality in these individuals is limited. This study aimed to evaluate genetic variants, epilepsy, and sleep patterns in SYNGAP1-associated syndrome patients and their caregivers. METHODS: An online survey was applied to 11 caregivers of individuals diagnosed with SYNGAP1-associated syndrome. Specific clinical inquiries were included, addressing childbirth, previous surgeries, and medication use. Inquiries about epilepsy included type of epilepsy, type and frequency of seizures, anti-seizure medications, and complementary non-pharmacological treatments. Children's Sleep Habits Questionnaire (CSHQ) was applied to assess the patients' sleep profile. Pittsburgh Sleep Quality Index (PSQI) was used to evaluate the sleep quality of caregivers. RESULTS: Genetic analysis showed heterozygous mutations in SYNGAP1, often leading to loss of function. Epilepsy was present in 82% of participants, with 77.8% having drug-resistant seizures. Using the Children's Sleep Habits Questionnaire (CSHQ), 81.8% of patients exhibited poor sleep habits, including bedtime resistance, anxiety, night awakenings, parasomnias, and daytime sleepiness. Caregivers also reported poor sleep quality according to the Pittsburgh Sleep Quality Index (PSQI). CONCLUSIONS: This study highlights the high prevalence of epilepsy and sleep problems in SYNGAP1-associated syndrome, impacting both patients and caregivers. Further research is crucial to understand the syndrome's effects on sleep disturbances, emphasizing the need for targeted interventions to improve sleep quality in individuals with rare genetic syndromes and their caregivers.

Two non-familial cases of Galloway-Mowat syndrome carrying the homozygous mutations of WDR73 and TP53RK / Dois casos não familiares de síndrome de Galloway-Mowat portadores das mutações homozigóticas de WDR73 e TP53RK

Galloway­Mowat syndrome (GAMOS) is a rare hereditary disease manifested as a combination of nephrotic syndrome and central nervous system impairment. To date, many GAMOS cases attributed to various gene mutations have been reported such as WHAMM, NUP107, WDR73, OSGEP, and TP53RK. We detected two novel homozygous mutations of WDR73 ''NM_032856:c.G287A:p.R96K'' and TP53RK ''NM_033550:c.A193O:p.K65Q'' in two female kids of the consanguineous parents from different families using whole exome sequencing. Both patients almost manifested similar neurodegenerative phenotypes, including developmental delay, microcephaly, hypotonia, and brain atrophy on magnetic resonance imaging during infancy. WDR73-positive GAMOS case manifested a lateonset minimal nephrotic syndrome at the age 4 years while TP53RK-positive case presented nephrotic syndrome at the age 1 which progressed to steroid-resistant nephrotic syndrome due to lack of remission after 4-6 weeks of initial treatment with prednisone. Despite the brain abnormalities and the onset time difference of renal abnormalities, both patients are still alive. Given the heterogeneity of the renal phenotype among GAMOS types, accurate recognition of expanding spectrum of phenotype findings and regular renal function screening are necessary for an early diagnosis and timely treatment

A síndrome de Galloway-Mowat (GAMOS) é uma doença hereditária rara que se manifesta como uma combinação de síndrome nefrótica e comprometimento do sistema nervoso central. Até o momento, foram relatados muitos casos de GAMOS atribuídos a várias mutações genéticas, como WHAMM, NUP107, WDR73, OSGEP e TP53RK. Detectamos duas novas mutações homozigóticas de WDR73 ''NM_032856:c.G287A:p.R96K'' e TP53RK ''NM_033550:c.A193O:p.K65Q'' em duas crianças do sexo feminino, de pais consanguíneos de diferentes famílias usando o exoma completo de sequenciamento. Ambos os pacientes manifestaram fenótipos neurodegenerativos semelhantes, incluindo atraso no desenvolvimento, microcefalia, hipotonia e atrofia cerebral por ressonância magnética durante a infância. O caso GAMOS positivo para WDR73 manifestou síndrome nefrótica mínima de início tardio aos quatro anos de idade, enquanto o caso positivo para TP53RK apresentou síndrome nefrótica com um ano de idade, que progrediu para síndrome nefrótica resistente a esteroides devido à falta de remissão após quatro a seis semanas de tratamento inicial com prednisona. Apesar das anormalidades cerebrais e da diferença de tempo de início das anormalidades renais, ambos os pacientes ainda estão vivos. Dada a heterogeneidade do fenótipo renal entre os tipos de GAMOS, o reconhecimento preciso do espectro em expansão dos achados fenótipos e a triagem regular da função renal são necessários para um diagnóstico precoce e tratamento oportuno

A Comprehensive Clinical Genetics Approach to Critical Congenital Heart Disease in Infancy.

OBJECTIVE: To investigate the frequency of genetic diagnoses among infants with critical congenital heart disease (CHD) using a comprehensive cardiovascular genetics approach and to identify genotype-phenotype correlations. STUDY DESIGN: A retrospective chart review of patients evaluated by cardiovascular genetics in a pediatric cardiac intensive care unit from 2010 to 2015 was performed. Infants with CHD who were <1 month of age were included. CHD was classified using structured phenotype definitions. Cardiac and noncardiac phenotypes were tested for associations with abnormal genetic testing using χ1 and Fisher exact tests. RESULTS: Genetic evaluation was completed in 293 infants with CHD, of whom 213 had isolated congenital heart disease (iCHD) and 80 had multiple congenital anomalies. Overall, the yield of abnormal genetic testing was 26%. The multiple congenital anomalies cohort had a greater yield of genetic testing (39%) than the iCHD cohort (20%) (OR 2.7). Using a non-hierarchical CHD classification and excluding 22q11.2 deletion and common aneuploidies, right ventricular obstructive defects were associated with abnormal genetic testing (P = .0005). Extracardiac features associated with abnormal genetic testing included ear, nose, and throat (P = .003) and brain (P = .0001) abnormalities. A diagnosis of small for gestational age or intrauterine growth retardation also was associated with abnormal genetic testing (P = .0061), as was presence of dysmorphic features (P = .0033, OR 3.5). Infants without dysmorphia with iCHD or multiple congenital anomalies had similar frequencies of abnormal genetic testing. CONCLUSIONS: The present study provides evidence to support a comprehensive cardiovascular genetics approach in evaluating infants with critical CHD while also identifying important genotype-phenotype considerations.

Management of the pseudobulbar affect (PBA) in Kabuki syndrome combined dextromethorphan-fluoxetine treatment as an alternative to dextromethorphan/quinidine

A case report of a patient with pseudo bulbar affect previous treatments included haloperidol (10mg), Inosina pranobex (600mg), clozapine (600mg), olanzapine (20mg), carbamazepine (200mg), paroxetine (20mg), phenobarbital (100mg) and topiramate (50mg), all suspended at August 2016, with current use of quetiapine (700mg) Chlorpromazine (600mg) (+ 200mg on demand of aggression), clonazepam (4 mg), valproate 2500 mg, propranolol (40mg). that was successful treated with off label treatment (dextromethorphan plus quinidine). Previous Brief Psychiatric Rating Scale and Clinical Global Impression-Improvement was applied after and before treatment with dextromethorphan (20mg) plus fluoxetine (20 mg, further increased to 40 mg). Previous Brief Psychiatric Rating Scale BPRS score 56 points and Clinical Global Impression-Severity (CGI-S) Score was 6 (severely ill). The addition of dextromethorphan (20mg) and fluoxetine (20 mg, further increased to 40 mg), allowed clear improvement of pathological crying and outbursts, with BPRS decrease of 8 points and Clinical Global Impression-Improvement (CGI-I) 2 (much improved) ­ especially pertaining to PBA related symptoms and aggressive behavior. There were no noticeable side-effects. This case report shown an interesting clinical response. It's could be a great alternative in treatment of pseudobulbar affect symptoms. Even though an only case and a great clinical study be necessary. (AU)

Copy Number Gain at Xq28 in a Child with Global Developmental Delay Associated with a Variant Form of Hoyeraal-Hreidarsson Syndrome.

We report the case of a child from Central Brazil with global developmental delay (GDD), syndromic features, and absence of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, with a rearrangement at Xq28 harboring the DKC1 gene. GTC-banding revealed a male karyotype (46,XY) with no visible numerical or structural alterations. Chromosomal microarray analysis (CMA) showed a 0.36-Mb gain at Xq28 of maternal origin, encompassing 22 genes, including DKC1. Rearrangements and mutations involving this gene have been associated with dyskeratosis congenita, X-linked (OMIM 305000) and Hoyeraal-Hreidarsson syndrome. CMA was a powerful and efficient approach to identify a gain at Xq28 harboring the DKC1 gene in our patient with GDD syndromic features and no cutaneous alterations, suggesting that this variant is associated with the Hoyeraal-Hreidarsson syndrome.

Consultorio de orientaciòn de cardilogía: epidemiología y perfil de la población / Cardiology guidance clinic: Epidemiology and profile of the population

Introducción: Las cardiopatías congénitas (CC) son las anomalías congénitas más frecuentes. Representan el 0,8-1,2% de todos los defectos del nacimiento y tienen una prevalencia de alrededor de 5,8 por cada 1000 personas. El Servicio de Cardiología del Hospital Garrahan es un centro de referencia nacional y de países limítrofes donde se realizan 18000 consultas anuales. Los pacientes que concurren por primera vez se atienden en el consultorio de orientación. Objetivo: Describir la epidemiologia y perfil de los pacientes que asisten diariamente al consultorio de orientación de cardiología infantil en un hospital pediátrico de tercer nivel de Buenos Aires. Métodos: Entre septiembre de 2017 y febrero de 2018 se recolectaron los datos de 1000 pacientes atendidos en forma consecutiva en el consultorio de orientación de cardiología. A la totalidad de los pacientes se les realizó anamnesis, examen físico cardiovascular, electrocardiograma, y en los casos en los que se consideró necesario, saturometría, radiografía de tórax y/o ecocardiograma. Las variables a considerar fueron edad, procedencia, presencia o ausencia de cardiopatías congénitas o adquiridas, soplo, cianosis, insuficiencia cardíaca, estado nutricional, síndromes genéticos asociados, métodos diagnósticos e indicaciones terapéuticas implementadas. Se subdividió la población en cinco grupos: Grupo A (pacientes con cardiopatía congénita), Grupo B (cardiopatías operadas), Grupo C (miocardiopatías), Grupo D (arritmias), Grupo E (corazón sano). Resultados: La edad mediana fue 4.86 años (0.03 a 18.9 años). El 64% de los pacientes procedían de la provincia de Buenos Aires. Los motivos de consulta fueron: interconsultas internas 29.5%, derivación por cardiopatía 27.2%, soplo 17.6%, síncope 7%, segunda opinión 5.1%, arritmias 4.8%, precordialgia 3.1%, palpitaciones 2.6%, episodio paroxístico 1.4%, cardiomegalia 0.7%, disnea 0.5%, mal progreso de peso 0.3%. El 10.6% tenían un síndrome genético. Grupo A: 252 pacientes con una edad mediana de 1.9 años. Las cardiopatías acianóticas con hiperflujo pulmonar fueron las más frecuentes (66.66%, 168/252). Grupo B: 51 pacientes, 23.52%(12/51) fueron Fallot reparados en otra institución. Grupo C: 22 pacientes, siendo la miocardiopatía hipertrófica la más frecuente. Grupo D: 47 pacientes, la preexcitación ventricular fue el hallazgo más frecuente (34,04%, 16/47). Grupo E: 628 pacientes, 45.70% (287/628) derivados por pediatras del área ambulatoria, principalmente para valoración de pacientes con enfermedades sistémicas o síndromes genéticos. Conclusión: Los motivos de derivación al consultorio de orientación de cardiología fueron muy diversos. La mayoría de los pacientes provenían de provincia de Buenos Aires. Solamente el 37.2% presentó algún problema cardiológico de base. El 91% de los pacientes que consultaron por soplo, no tuvieron cardiopatía. El grupo correspondiente a los pacientes con cardiopatías no operadas (grupo A) fue el de menor edad (mediana de 1.9 años) y las cardiopatías simples no cianóticas con hiperflujo pulmonar representaron el 66.66% de las cardiopatías. La implementación del ecocardiograma portátil en el consultorio de orientación permitió confirmar el diagnóstico y definir la conducta terapéutica en el 29.4% de los pacientes durante la primer consulta (AU)

Introduction: Congenital heart defects (CHD) are the most common congenital abnormalities. They account for 0.8-1.2% of all birth defects and have a prevalence of around 5.8 per 1000 people. The Department of Cardiology of Garrahan Hospital is a national and bordering-country reference center, receiving 18000 consultations annually. Patients seen for the first time are assessed at the cardiology guidance clinic. Objective: To describe the epidemiology and profile of patients who seen daily at the child cardiology guidance clinic of a third-level pediatric hospital in Buenos Aires. Methods: Between September 2017 and February 2018, data from 1000 patients consecutively seen at the cardiology guidance clinic were collected. All patients underwent anamnesis, cardiovascular physical examination, electrocardiogram and, if considered necessary, pulse oximetry, chest x-ray, and/or echocardiogram. The variables considered were age, place of origin, presence or absence of congenital or acquired heart disease, murmur, cyanosis, heart failure, nutritional status, associated genetic syndromes, diagnostic methods, and treatment. The population was divided into five groups: Group A (patients with congenital heart defects), Group B (operated cardiopathies), Group C (myocardiopathies), Group D (arrhythmias), Group E (healthy heart). Results: Median age was 4.86 years (0.03 to 18.9 years). Overall, 64% of patients came from the province of Buenos Aires. The reasons for consultation were: internal consultations 29.5%, cardiac shunt 27.2%, murmur 17.6%, syncope 7%, second opinion 5.1%, arrhythmias 4.8%, precordialgia 3.1%, palpitations 2.6%, paroxysmal episode 1.4%, cardiomegaly 0.7%, dyspnea 0.5%, 0.3% poor weight gain. A genetic syndrome was identified in 10.6%. Group A: 252 patients with a median age of 1.9 years. Acyanotic congenital heart defect with pulmonary hyperflow was the most common (66.66%, 168/252). Group B: 51 patients, 23.52% (12/51) had tetralogy of Fallot repaired at another institution. Group C: 22 patients, in whom hypertrophic cardiomyopathy was the most common. Group D: 47 patients, in whom ventricular preexcitation was the most common finding (34.04%, 16/47). Group E: 628 patients, 45.70% (287/628) referred by pediatricians from the outpatient clinics, mainly for the assessment of systemic diseases or genetic syndromes. Conclusion: The reasons for referral to the cardiology guidance clinic were varied. Most of the patients came from the province of Buenos Aires. Only 37.2% had an underlying heart disease. Of the patients who consulted because of a murmur, 91% did not suffer from heart disease. The group of patients with congenital heart disease who had not undergone surgery (group A) was the youngest (median 1.9 years) and simple non-cyanotic heart disease with pulmonary hyperflow accounted for 66.66% of heart diseases. The implementation of the portable echocardiography in the guidance clinic confirmed the diagnosis and defined the management in 29.4% of patients during the first consultation (AU)

Skeletal abnormalities of tricho-rhino-phalangeal syndrome type I.

The tricho-rhino-phalangeal syndrome (TRPS) type I is a rare genetic disorder related to the TRPS1 gene mutation in chromosome 8, characterized by craniofacial abnormalities and disturbances in formation and maturation of bone matrix. The hallmarks are sparse and brittle hair, tendency to premature baldness, bulbous nose called pear-shaped, long and flat filter and low ear implantation. The most noticeable skeletal changes are clinodactyly, phalangeal epiphyses of the hands appearing as cone-shaped, short stature and hip joint malformations. We report a case of a teenager boy diagnosed with TRPS and referred for rheumatologic evaluation due to joint complaints.

Anormalidades esqueléticas da síndrome tricorrinofalangiana tipo I / Skeletal abnormalities of tricho-rhino-phalangeal syndrome type I

Resumo A síndrome tricorrinofalangiana (STRF) tipo I é uma doença genética rara, relacionada com a mutação no gene TRPS1 do cromossomo 8. É caracterizada por anomalias craniofaciais e distúrbios na formação e maturação da matriz óssea. As características são cabelos ralos e quebradiços, tendência à calvície prematura, nariz bulboso em formato de pera, filtro nasal longo e plano e baixa implantação das orelhas. As alterações esqueléticas mais notáveis são a clinodactilia, as epífises das falanges das mãos em forma de cone, a baixa estatura e as malformações na articulação do quadril. Relata-se o caso de um adolescente diagnosticado com STRF e encaminhado para avaliação reumatológica em decorrência de queixas articulares.

Abstract The tricho-rhino-phalangeal syndrome (TRPS) type I is a rare genetic disorder related to the TRPS1 gene mutation in chromosome 8, characterized by craniofacial abnormalities and disturbances in formation and maturation of bone matrix. The hallmarks are sparse and brittle hair, tendency to premature baldness, bulbous nose called pear-shaped, long and flat filter and low ear implantation. The most noticeable skeletal changes are clinodactyly, phalangeal epiphyses of the hands appearing as cone-shaped, short stature and hip joint malformations. We report a case of a teenager boy diagnosed with TRPS and referred for rheumatologic evaluation due to joint complaints.

Obesity and its association with generalised epilepsy, idiopathic syndrome, and family history of epilepsy.

Aim. Previous studies support the concept that obesity is a common comorbid condition in patients with epilepsy (PWE). In this study, we present the body mass index (BMI) and data from a survey to assess physical activity in a sample of PWE from an epilepsy clinic. Methods. Between June of 2011 and January of 2013, 100 PWE from an adult epilepsy clinic were included. We obtained BMI, waist circumference, and information regarding physical activity using a standardised questionnaire. Clinical, demographic, electrographic, and imaging parameters were collected from charts. Results. Mean age of patients was 40 ± 14 (18-77) years. The BMI distribution was as follows: 2 patients (2%) underweight, 26 (26%) normal weight, 34 (34%) overweight, 25 (25%) obese, and 13 (13%) with morbid obesity. In our study, obesity was defined as having a BMI ≥ 30. We found 38 (38%) patients in this range. There was no difference in the rate of drug-resistant epilepsy between obese and non-obese patients (55 vs. 55%; p=0.05). Leisure time habit was reported in 82% of obese patients and 79% of patients without obesity. Overall, the most frequent activity was walking (70%). Factors associated with obesity were generalised epilepsy (OR: 2.7, 1.1-6.6; p=0.012), idiopathic syndrome (OR: 2.7, 1.04-7; p=0.018), and family history of epilepsy (OR: 6.1, 1.5-24.2; p=0.002). Conclusion. Our study suggests an association between obesity, idiopathic generalised epilepsy, and family history of epilepsy. Our study shows that PWE are physically active and there is no clear relation between exercise and obesity. We could not identify any association between drug-resistant epilepsy and obesity. Absence of direct comparison with a control non-epileptic population; a cross-sectional design not allowing evaluation of a causal association among variables; and reliance on self-reported physical activity are to be considered as limitations of the present study.