Hidden etiology of cerebral palsy: genetic and clinical heterogeneity and efficient diagnosis by next-generation sequencing.

Cerebral palsy (CP) is a heterogeneous neurodevelopmental disorder that causes movement and postural disabilities. Recent research studies focused on genetic diagnosis in patients with CP of unknown etiology. The present study was carried out in 20 families with one family member affected with idiopathic CP. Chromosomal microarray and exome sequencing techniques were performed in all patients. Chromosomal microarray analysis did not show any pathological or probable pathological structural variant. However, the next-generation sequencing study showed a high diagnostic yield. We report 11/20 patients (55%) with different pathogenic or potentially pathogenic variants detected by exome sequencing analysis: five patients with mutations in genes related to hereditary spastic paraplegia, two with mutations in genes related to Aicardi-Goutières syndrome, three with mutations in genes related to developmental/epileptic encephalopathies, and one with a mutation in the PGK1 gene. The accurate and precise patients' selection, the use of a high-throughput genetic platform, the selection of adequate target genes, and the application of rigorous criteria for the clinical interpretation are the most important elements for a good diagnostic performance. Based on our findings, next-generation sequencing should be considered in patients with cryptogenic CP as the first line of genetic workup. IMPACT: Sequencing techniques in CP of uncertain etiology provides a diagnostic yield of 55%. The appropriate selection of cases optimizes the diagnostic yield. NGS facilitate better understanding of new phenotypes of certain genetic diseases.

Standing and Responding in Solidarity with Disenfranchised Immigrant Families in the United States: An Ongoing Call for Action.

The status of immigrant families resettled to the United States in the past decade has been fraught with upsurges of governmental policies that have systematically increasing the levels of oppression, violence, and abuses of human rights. The socio-political-economic toll of xenophobic practices on specifically targeted immigrant populations is magnified by the psychological and relational impact they have on individuals, families, and communities. This manuscript is conceptualized as an ongoing call for social action and specific mobilization by mental health professionals in response to the increasing threats to civility and dignity faced by various immigrant communities. The paper is organized in three sections: (a) an overview of the effects of immigration policy on immigrant family experiences; (b) the impact of mental and relational health on immigrant populations; and (c) elaborations of three exemplar community projects designed to support immigrant families. The manuscript concludes with a discussion exploring avenues for promoting a stronger base for solidarity and social action.

Spanish Translation, Cultural Adaptation, and Validation of the Standardized Cosmesis and Health Nasal Outcomes Survey Questionnaire.

BACKGROUND: The Standardized Cosmesis and Health Nasal Outcomes Survey (SCHNOS) questionnaire is a new instrument that was developed to evaluate both functional and cosmetic components of rhinoplasty. It is a reliable, consistent, and validated patient-reported outcome measure that is not available in Spanish. METHODS: The SCHNOS questionnaire was forward translated, back translated, and culturally adapted following international guidelines. Its psychometric validity was tested with native Spanish speakers in 2 centers in Colombia. The authors measured internal consistency, correlation, and reproducibility to determine validity of the instrument. RESULTS: The final Spanish version of the SCHNOS was administered to 76 native Spanish speakers. Both the SCHNOS-O (obstructive domain) and SCHNOS-C (cosmetic domain) showed a high internal consistency with Cronbach's alpha of 0.84 and 0.94, respectively. The Spearman correlations between the items of SCHNOS-O (0.38-0.82) and SCHNOS-C (0.49-0.88) were positive and significant. Spearman's rank correlation in the test-retest analysis for SCHNOS-O (r = 0.87) and SCHNOS-C (r = 90) was positive and statistically significant. There was statistical significance in responses obtained for SCHNOS-O (P < 0.001) but not for SCHNOS-C (P = 0.222). CONCLUSIONS: In this study, the SCHNOS was successfully translated and culturally adapted into Spanish. The Spanish version of the SCHNOS was shown to be a reliable and valid instrument that we recommend it should be used in Spanish-speaking patients who are having functional or cosmetic rhinoplasty.

Remnant lipoprotein size distribution profiling via dynamic light scattering analysis.

BACKGROUND: Remnant lipoproteins (RLP) are a metabolically derived subpopulation of triglyceride-rich lipoproteins (TRL) in human blood that are involved in the metabolism of dietary fats or triglycerides. RLP, the smaller and denser variants of TRL particles, are strongly correlated with cardiovascular disease (CVD) and were listed as an emerging atherogenic risk factor by the AHA in 2001. METHODS: Varying analytical techniques used in clinical studies in the size determination of RLP contribute to conflicting hypotheses in regard to whether larger or smaller RLP particles contribute to CVD progression, though multiple pathways may exist. RESULTS: We demonstrated a unique combinatorial bioanalytical approach involving the preparative immunoseparation of RLP, and dynamic light scattering for size distribution analysis. CONCLUSIONS: This is a new facile and robust methodology for the size distribution analysis of RLP that in conjunction with clinical studies may reveal the mechanisms by which RLP cause CVD progression.

[Hypomyelination with atrophy of the basal ganglia and cerebellum. Contribution of two new cases to a recently reported entity]. / Hipomielinización con atrofia de ganglios basales y de cerebelo. Aportación de dos nuevos casos a una entidad de descripción reciente.

INTRODUCTION: Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare condition that has only recently been reported. Here we present two new cases belonging to the same family. CASE REPORTS: Case 1: 17-month-old boy with severe underdevelopment in all areas, absence of language and eye contact. The examination revealed microcephaly with spastic tetraparesis. A magnetic resonance imaging scan showed predominantly vermian atrophy of the cerebellum with loss of volume of both nuclei of the putamen and the head of the caudate, and a pattern of hypomyelination of the white matter. Electromyography recording highlighted the presence of a predominantly motor pattern of chronic polyneuropathy. Homovallinic acid and 5-hydroxyindoleacetic acid values were lower than usual. Treatment with levodopa/carbidopa was not effective. Case 2: 11-month-old girl, the sister of the boy in the previous case. The patient presented severe underdevelopment in all areas and microcephaly with spastic tetraparesis was detected in the clinical examination. Magnetic resonance imaging of the head showed findings that could be superimposed upon those of the brother, with hypomyelination, cerebellar atrophy and involvement of the putamen and both caudates; electromyography findings were consistent with motor polyneuropathy of a demyelinating nature. Homovallinic acid and 5-hydroxyindoleacetic acid values in cerebrospinal fluid were lower than usual. Treatment with levodopa/carbidopa was ineffective. CONCLUSIONS: These two new cases help characterise this condition better and reinforce the hypothesis of the genetic origin of the syndrome, given that the two cases occurred in the same family.

TITLE: Hipomielinizacion con atrofia de ganglios basales y de cerebelo. Aportacion de dos nuevos casos a una entidad de descripcion reciente.Introduccion. La hipomielinizacion con atrofia de ganglios basales y de cerebelo (H-ABC) es una rara entidad descrita recientemente. Se presentan dos nuevos casos pertenecientes a una misma familia. Casos clinicos. Caso 1: niño de 17 meses con retraso grave en todas las areas, ausencia de lenguaje y de contacto visual. En la exploracion destacaba una microcefalia con tetraparesia espastica. En la resonancia magnetica cerebral se apreciaba atrofia cerebelosa de predominio vermiano con perdida de volumen de ambos nucleos del putamen y la cabeza del caudado, y patron de hipomielinizacion de la sustancia blanca. En la electromiografia se objetivo un patron de polineuropatia cronica de predominio motor. Presento un descenso de los valores de acido homovalinico y de acido 5-hidroxindolacetico. El tratamiento con levodopa/carbidopa no fue efectivo. Caso 2: niña de 11 meses, hermana del caso anterior. Presentaba un retraso grave en todas las areas y en la exploracion clinica se detecto una microcefalia con tetraparesia espastica. La resonancia magnetica cerebral mostro hallazgos superponibles a los del hermano, con hipomielinizacion, atrofia cerebelosa y afectacion putaminal y de ambos caudados; en la electromiografia, hallazgos compatibles con polineuropatia motora de caracter desmielinizante. Presento un descenso de los valores de acido homovalinico y acido 5-hidroxindolacetico en el liquido cefalorraquideo. El tratamiento con levodopa/carbidopa resulto ineficaz. Conclusiones. Estos dos nuevos casos ayudan a caracterizar mejor esta entidad y refuerzan la hipotesis del origen genetico del sindrome, dado que se trata de dos casos pertenecientes a una misma familia.

Hipomielinización con atrofia de ganglios basales y de cerebelo. Aportación de dos nuevos casos a una entidad de descripción reciente / Hypomyelination with atrophy of the basal ganglia and cerebellum. Contribution of two new cases to a recently reported entity

Introducción. La hipomielinización con atrofia de ganglios basales y de cerebelo (H-ABC) es una rara entidad descrita recientemente. Se presentan dos nuevos casos pertenecientes a una misma familia. Casos clínicos. Caso 1: niño de 17 meses con retraso grave en todas las áreas, ausencia de lenguaje y de contacto visual. En la exploración destacaba una microcefalia con tetraparesia espástica. En la resonancia magnética cerebral se apreciaba atrofia cerebelosa de predominio vermiano con pérdida de volumen de ambos núcleos del putamen y la cabeza del caudado, y patrón de hipomielinización de la sustancia blanca. En la electromiografía se objetivó un patrón de polineuropatía crónica de predominio motor. Presentó un descenso de los valores de ácido homovalínico y de ácido 5-hidroxindolacético. El tratamiento con levodopa/carbidopa no fue efectivo. Caso 2: niña de 11 meses, hermana del caso anterior. Presentaba un retraso grave en todas las áreas y en la exploración clínica se detectó una microcefalia con tetraparesia espástica. La resonancia magnética cerebral mostró hallazgos superponibles a los del hermano, con hipomielinización, atrofia cerebelosa y afectación putaminal y de ambos caudados; en la electromiografía, hallazgos compatibles con polineuropatía motora de carácter desmielinizante. Presentó un descenso de los valores de ácido homovalínico y ácido 5-hidroxindolacético en el líquido cefalorraquídeo. El tratamiento con levodopa/carbidopa resultó ineficaz. Conclusiones. Estos dos nuevos casos ayudan a caracterizar mejor esta entidad y refuerzan la hipótesis del origen genético del síndrome, dado que se trata de dos casos pertenecientes a una misma familia (AU)

Introduction. Hypomyelination with atrophy of the basal ganglia and cerebellum (H-ABC) is a rare condition that has only recently been reported. Here we present two new cases belonging to the same family. Case reports. Case 1: 17-month-old boy with severe underdevelopment in all areas, absence of language and eye contact. The examination revealed microcephaly with spastic tetraparesis. A magnetic resonance imaging scan showed predominantly vermian atrophy of the cerebellum with loss of volume of both nuclei of the putamen and the head of the caudate, and a pattern of hypomyelination of the white matter. Electromyography recording highlighted the presence of a predominantly motor pattern of chronic polyneuropathy. Homovallinic acid and 5-hydroxyindoleacetic acid values were lower than usual. Treatment with levodopa/carbidopa was not effective. Case 2: 11-month-old girl, the sister of the boy in the previous case. The patient presented severe underdevelopment in all areas and microcephaly with spastic tetraparesis was detected in the clinical examination. Magnetic resonance imaging of the head showed findings that could be superimposed upon those of the brother, with hypomyelination, cerebellar atrophy and involvement of the putamen and both caudates; electromyography findings were consistent with motor polyneuropathy of a demyelinating nature. Homovallinic acid and 5-hydroxyindoleacetic acid values in cerebrospinal fluid were lower than usual. Treatment with levodopa/carbidopa was ineffective. Conclusions. These two new cases help characterise this condition better and reinforce the hypothesis of the genetic origin of the syndrome, given that the two cases occurred in the same family (AU)