RESUMEN
Resumen El trastorno por déficit de atención/hiperactividad (TDAH) es un trastorno del neurodesarrollo complejo y heterogéneo desde una perspectiva causal, clínica y pro nóstica. La investigación refleja su carácter multifactorial con un papel destacado de los factores genéticos. Los estudios poblacionales han señalado históricamente la implicación de numerosas variantes genéticas de escaso tamaño de efecto, las cuales por sí mismas apenas incre mentan el riesgo de TDAH y difícilmente justifican su ele vada heredabilidad. Muchas de ellas están presentes en más del 60% de la población general, lo que sugiere su pa pel modulador más que causal. No obstante, gracias a la irrupción de nuevas técnicas genéticas en los últimos 15 años, se están identificando un mayor número de casos con trastornos genéticos (muchos de ellos monogénicos), cuyas variantes genéticas explican por sí mismas la presencia del TDAH. El estudio detallado de los antecedentes personales y familiares, así como una exploración física completa, puede ayudar a identificar algunos de ellos. La identificación de la causa en este conjunto de casos tiene un valor crucial en el asesoramiento clínico, el consejo genético-familiar y la anticipación pronóstica, así como en la realización o evitación de estudios complementarios y en el diseño del plan terapéutico.
Abstract Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous neurodevelopmental disor der from a causal, clinical and prognostic perspective. Research reflects its multifactorial nature with a promi nent role of genetic factors. Population studies have historically pointed to the involvement of numerous genetic variants of small effect size, which hardly by themselves increase the risk of presenting the disorder and hardly justify its high heritability. Many of them are present in more than 60% of the general population, suggesting their modulatory rather than causal role. However, after the irruption of new genetic techniques in the last 15 years, a greater number of cases are be ing identified with genetic disorders (many of them monogenic), whose genetic variants alone explain the presence of ADHD. A detailed study of the personal and family history, as well as a complete physical examination, can help to identify some of them. The identification of the cause in this group of cases has a crucial value in clinical counseling, genetic-familial counseling and prognostic anticipation, as well as in the performance or avoidance of complementary stud ies and in the design of the intervention plan.
RESUMEN
Attention-deficit/hyperactivity disorder (ADHD) is a complex and heterogeneous neurodevelopmental disorder from a causal, clinical and prognostic perspective. Research reflects its multifactorial nature with a prominent role of genetic factors. Population studies have historically pointed to the involvement of numerous genetic variants of small effect size, which hardly by themselves increase the risk of presenting the disorder and hardly justify its high heritability. Many of them are present in more than 60% of the general population, suggesting their modulatory rather than causal role. However, after the irruption of new genetic techniques in the last 15 years, a greater number of cases are being identified with genetic disorders (many of them monogenic), whose genetic variants alone explain the presence of ADHD. A detailed study of the personal and family history, as well as a complete physical examination, can help to identify some of them. The identification of the cause in this group of cases has a crucial value in clinical counseling, genetic-familial counseling and prognostic anticipation, as well as in the performance or avoidance of complementary studies and in the design of the intervention plan.
El trastorno por déficit de atención/hiperactividad (TDAH) es un trastorno del neurodesarrollo complejo y heterogéneo desde una perspectiva causal, clínica y pronóstica. La investigación refleja su carácter multifactorial con un papel destacado de los factores genéticos. Los estudios poblacionales han señalado históricamente la implicación de numerosas variantes genéticas de escaso tamaño de efecto, las cuales por sí mismas apenas incrementan el riesgo de TDAH y difícilmente justifican su elevada heredabilidad. Muchas de ellas están presentes en más del 60% de la población general, lo que sugiere su papel modulador más que causal. No obstante, gracias a la irrupción de nuevas técnicas genéticas en los últimos 15 años, se están identificando un mayor número de casos con trastornos genéticos (muchos de ellos monogénicos), cuyas variantes genéticas explican por sí mismas la presencia del TDAH. El estudio detallado de los antecedentes personales y familiares, así como una exploración física completa, puede ayudar a identificar algunos de ellos. La identificación de la causa en este conjunto de casos tiene un valor crucial en el asesoramiento clínico, el consejo genético-familiar y la anticipación pronóstica, así como en la realización o evitación de estudios complementarios y en el diseño del plan terapéutico.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Trastornos del Neurodesarrollo , Humanos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/genética , Proyectos de Investigación , Predisposición Genética a la EnfermedadRESUMEN
Tatton-Brown-Rahman syndrome (TBRS) or DNMT3A-overgrowth syndrome is characterized by overgrowth and intellectual disability associated with minor dysmorphic features, obesity, and behavioral problems. It is caused by variants of the DNMT3A gene. We report four patients with this syndrome due to de novo DNMT3A pathogenic variants, contributing to a deeper understanding of the genetic basis and pathophysiology of this autosomal dominant syndrome. Clinical and magnetic resonance imaging assessments were also performed. All patients showed corpus callosum anomalies, small posterior fossa, and a deep left Sylvian fissure; as well as asymmetry of the uncinate and arcuate fascicles and marked increased cortical thickness. These results suggest that structural neuroimaging anomalies have been previously overlooked, where corpus callosum and brain tract alterations might be unrecognized neuroimaging traits of TBRS syndrome caused by DNMT3A variants.
Asunto(s)
Anomalías Múltiples , Discapacidad Intelectual , Anomalías Musculoesqueléticas , Humanos , Discapacidad Intelectual/diagnóstico por imagen , Discapacidad Intelectual/genética , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Anomalías Múltiples/genética , Anomalías Musculoesqueléticas/complicaciones , Síndrome , NeuroimagenRESUMEN
Resumen Más allá de la frecuente coexistencia del trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno específico del aprendizaje de la lectura, la presente revisión pretende examinar la evidencia empírica disponible sobre cómo el TDAH impacta negativamente sobre el aprendizaje de la lectura. Los datos existentes apuntan a que la presencia del trastorno (especialmente los síntomas de falta de atención), puede afectar a i) la correcta adquisición de lectura, ya sea de manera directa o a través de su influencia sobre los precursores de la lectura; ii) las propias habilidades de decodificación (precisión y fluidez lectora), tanto de manera directa como indirecta a través de su influencia sobre procesos cognitivos como la distracción o las funciones ejecutivas; y ii) la comprensión lectora, probablemente de manera indirecta por las dificultades eje cutivas y en la memoria de trabajo verbal características del TDAH. Estas conclusiones presentan importantes implicaciones para caracterizar e intervenir mejor sobre las dificultades lectoras en el TDAH, ya sean clínicas o subclínicas.
Abstract Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading dis order (dyslexia), the present review aims to examine the available empirical evidence on how ADHD negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symp toms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.
RESUMEN
Beyond the frequent coexistence of attention deficit hyperactivity disorder (ADHD) and reading disorder (dyslexia), the present review aims to examine the available empirical evidence on how ADHD negatively impacts on learning to read. Existing data suggest that the presence of the disorder (especially inattention symptoms), may affect i) the correct acquisition of reading, either directly or through its influence on the precursors to reading; ii) decoding skills themselves (reading accuracy and fluency), both directly and indirectly through its influence on cognitive processes such as distractibility or executive functions; and iii) reading comprehension, probably indirectly through the executive and verbal memory difficulties characteristic of ADHD. These findings have important implications for better characterizing and intervening on reading difficulties in ADHD, whether clinical or subclinical.
Más allá de la frecuente coexistencia del trastorno por déficit de atención con hiperactividad (TDAH) y el trastorno específico del aprendizaje de la lectura, la presente revisión pretende examinar la evidencia empírica disponible sobre cómo el TDAH impacta negativamente sobre el aprendizaje de la lectura. Los datos existentes apuntan a que la presencia del trastorno (especialmente los síntomas de falta de atención), puede afectar a i) la correcta adquisición de lectura, ya sea de manera directa o a través de su influencia sobre los precursores de la lectura; ii) las propias habilidades de decodificación (precisión y fluidez lectora), tanto de manera directa como indirecta a través de su influencia sobre procesos cognitivos como la distracción o las funciones ejecutivas; y ii) la comprensión lectora, probablemente de manera indirecta por las dificultades ejecutivas y en la memoria de trabajo verbal características del TDAH. Estas conclusiones presentan importantes implicaciones para caracterizar e intervenir mejor sobre las dificultades lectoras en el TDAH, ya sean clínicas o subclínicas.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Dislexia , Humanos , Trastorno por Déficit de Atención con Hiperactividad/complicaciones , Comprensión , Aprendizaje , Cognición , Función Ejecutiva , Dislexia/complicaciones , Dislexia/psicologíaRESUMEN
Bi-allelic mutations in the TUBGCP4 gene have been recently associated with autosomal recessive microcephaly with chorioretinopathy. However, little is known about the genotype-phenotype characteristics of this disorder. Here, we describe a 5-year-old male patient with autism and a normal occipitofrontal circumference. No retinal abnormalities were observed. Brain MRI revealed the presence of enlarged sheaths of both tortuous optic nerves; both eyes had shorter axial lengths. Whole-exome sequencing in trio revealed synonymous TUBGCP4 variants in homozygous state: c.1746G>T; p.Leu582=. This synonymous variant has been previously described and probably leads to skipping of exon 16 of TUBGCP4. These results broaden the clinical spectrum of this new syndrome and suggest that TUBGCP4 bi-allelic mutations may underlie complex neurodevelopmental disorders.
RESUMEN
Mutations in the PQBP1 gene are associated with Renpenning syndrome (RENS1, MIM# 309500). Most cases are characterized by intellectual disability, but a detailed neuropsychological profile has not yet been established. The present case study of a 8.5 years-old male child with a missense novel mutation in the PQBP1 gene expands existing understanding of this syndrome by presenting a milder clinical and neuropsychological phenotype. Whole exome trio analysis sequencing revealed a maternally inherited PQBP1 missense mutation in chromosome X [NM_001032383.1, c.727C > T (p.Arg243Trp)]. Variant functional studies demonstrated a significant reduction in the interaction between PQBP1 and the component of the nuclear pre-mRNA splicing machinery, U5-15KD. A comprehensive neuropsychological assessment revealed marked deficits in processing speed, attention and executive functioning (including planning, inhibitory control and working memory) without intellectual disability. Several components of language processing were also impaired. These results support that this mutation partially disrupts the function of this gene, which is known to play critical roles in embryonic and neural development. As most of the genomic PQBP1 abnormalities associated with intellectual disability have been found to be loss-of-function mutations, we hypothesize that a partial loss-of-function of this variant is associated with a mild behavioral and neuropsychological phenotype.
Asunto(s)
Discapacidad Intelectual , Mutación Missense , Proteínas Portadoras/genética , Parálisis Cerebral , Proteínas de Unión al ADN/genética , Humanos , Discapacidad Intelectual/genética , Masculino , Herencia Materna , Discapacidad Intelectual Ligada al Cromosoma X , Proteínas Nucleares/genética , Fenotipo , Precursores del ARNRESUMEN
The engulfment and cell motility 3 (ELMO3) protein belongs to the ELMO-family of proteins. ELMO proteins form a tight complex with the DOCK1-5 guanine nucleotide exchange factors that regulate RAC1 spatiotemporal activation and signalling. DOCK proteins and RAC1 are known to have fundamental roles in central nervous system development. Here, we searched for homozygous or compound heterozygous mutations in the ELMO3 gene in 390 whole exomes sequenced in trio in individuals with neurodevelopmental disorders compatible with a genetic origin. We found a compound heterozygous mutation in ELMO3 (c.1153A>T, p.Ser385Cys and c.1009 G > A, p.Val337Ile) in a 5 year old male child with autism spectrum disorder (ASD) and developmental delay. These mutations did not interfere with the formation of an ELMO3/DOCK1 complex, but markedly impaired the ability of the complex to promote RAC1-GTP-loading. Consequently, cells expressing DOCK1 and either of the ELMO3 mutants displayed impaired migration and invasion. Collectively, our results suggest that biallelic loss-of-function mutations in ELMO3 may cause a developmental delay and provide new insight into the role of ELMO3 in neurodevelopmental as well as the pathological consequences of ELMO3 mutations.
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Trastorno del Espectro Autista , Discapacidad Intelectual , Masculino , Niño , Humanos , Preescolar , Discapacidad Intelectual/genética , Factores de Intercambio de Guanina Nucleótido/genética , Factores de Intercambio de Guanina Nucleótido/metabolismo , Mutación , Transducción de Señal , Factores de Transcripción/metabolismo , Proteína de Unión al GTP rac1/genética , Proteína de Unión al GTP rac1/metabolismo , Proteínas del Citoesqueleto/genética , Proteínas del Citoesqueleto/metabolismo , Proteínas Adaptadoras Transductoras de Señales/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismoRESUMEN
KBG syndrome is characterized by dental, craniofacial and skeletal anomalies, short stature and global developmental delay or intellectual disability. It is caused by microdeletions or truncating mutations of ANKRD11. We report four unrelated probands with this syndrome due to de novo ANKRD11 aberrations that may contribute to a better understanding of the genetics and pathophysiology of this autosomal dominant syndrome. Clinical, cognitive and MRI assessments were performed. Three of the patients showed normal intellectual functioning, whereas the fourth had a borderline level of intellectual functioning. However, all of them showed deficits in various cognitive and socioemotional processes such as attention, executive functions, empathy or pragmatic language. Moreover, all probands displayed marked asymmetry of the uncinate fascicles and an abnormal gyrification pattern in the left frontal lobe. Thus, structural neuroimaging anomalies seem to have been overlooked in this syndrome. Disturbed frontal gyrification and/or lower structural integrity of the uncinate fascisulus might be unrecognized neuroimaging features of KBG syndrome caused by ANKRD11 aberrations. Present results also point out that this syndrome is not necessarily associated with global developmental delay and intellectual disability, but it can be related to other neurodevelopmental disorders or subclinical levels of attention-deficit hyperactivity disorder, autism, communication disorders or specific learning disabilities.
Asunto(s)
Anomalías Múltiples , Enfermedades del Desarrollo Óseo , Discapacidad Intelectual , Proteínas Represoras , Anomalías Dentarias , Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/genética , Enfermedades del Desarrollo Óseo/diagnóstico por imagen , Enfermedades del Desarrollo Óseo/genética , Facies , Humanos , Discapacidad Intelectual/diagnóstico por imagen , Discapacidad Intelectual/genética , Fenotipo , Proteínas Represoras/genética , Anomalías Dentarias/diagnóstico por imagen , Anomalías Dentarias/genéticaRESUMEN
Mutations in the ANO3 gene have been associated with autosomal dominant craniocervical dystonia. However, little else is known about the genotype-phenotype characteristics of this disorder. Here we describe a 3 years-old girl with distal myoclonic dystonia. Whole exome sequencing in trio revealed a de novo missense ANO3 variant not previously described in international databases. A global psychomotor regression was observed once dystonia was present. Brain MRI changes paralleled these findings: whereas MRI at the age of 18 months was normal, mild brain and cerebellar atrophy was observed 18 months later. These results suggest that missense mutations in ANO3 may underlie complex disorders particularly characterized by early psychomotor regression and dystonia.
Asunto(s)
Anoctaminas/genética , Encefalopatías/genética , Trastornos Distónicos/genética , Trastornos Psicomotores/genética , Edad de Inicio , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Cerebelo/diagnóstico por imagen , Preescolar , Trastornos Distónicos/diagnóstico por imagen , Trastornos Distónicos/patología , Femenino , Humanos , Mutación Missense , Trastornos Psicomotores/diagnóstico por imagen , Trastornos Psicomotores/patologíaRESUMEN
INTRODUCTION: Attention-deficit/hyperactivity disorder (ADHD) is one of the most prevalent disorders in the child and adolescent population, with a known impact on learning, social relations and quality of life. However, the lifestyle habits of patients with this disorder have been poorly studied. MATERIAL AND METHODS: A total of 160 children and adolescents, aged between 6 and 16 years, participated in the study. Half of them were treatment-naïve patients with a clinical diagnosis of ADHD according to DSM-IV-TR criteria, and without comorbidities. The remaining 80 participants were typically developing (TD) controls without known neurodevelopmental or psychiatric disorders. Parents of all participants completed a questionnaire about their children´s lifestyle habits (e.g, daily hours of sleep, media use and study). RESULTS: The groups had a similar socioeconomic background and did not differ with respect to age and sex distribution. However, patients with ADHD spent more time than TD children studying, and less time watching TV, playing video games, using computers and playing with other people. They also slept fewer hours per night than children and adolescents with TD. ADHD and TD groups spent similar time reading, listening to music and playing sports. CONCLUSIONS: The results of this study suggest that children and adolescents with ADHD have different lifestyle habits compared to age- and sex-matched controls. These findings are not explained by comorbid disorders or medication/ psychological treatment.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/psicología , Hábitos , Estilo de Vida , Adolescente , Niño , Conducta Infantil , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Femenino , Humanos , Masculino , Padres , Encuestas y Cuestionarios , Juegos de VideoRESUMEN
OBJECTIVE: This study aimed to examine the influence of dopamine transporter gene ( DAT1) 3'UTR genotype on cingulate cortical thickness in a large sample of children and adolescents with ADHD. METHOD: Brain MRIs were acquired from 46 ADHD patients with homozygosity for the 10-repeat allele and 52 ADHD patients with a single copy or no copy of the allele. The cingulate cortex of each MRI scan was automatically parceled into sulci and gyri as well as into Brodmann areas (BA). RESULTS: There were no group differences in age, gender, full-scale intelligence quotient, symptom severity, treatment status, comorbidity, or mean overall cortical thickness. Sulcus/gyrus- and BA-based analyses revealed that patients homozygous for the 10-repeat allele showed significantly greater thickness in right cingulate gyrus and right BA 24 compared with 9-repeat carriers. CONCLUSION: These findings suggest that thickness of cingulate cortex is influenced by the presence of the 10-repeat allele in ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Giro del Cíngulo/patología , Polimorfismo Genético/genética , Adolescente , Alelos , Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/patología , Niño , Femenino , Genotipo , Homocigoto , Humanos , Imagen por Resonancia Magnética , MasculinoRESUMEN
We describe a 4-year-old male child born to non-consanguineous Spanish parents with progressive encephalopathy (PE), microcephaly, and hypertonia. Whole exome sequencing revealed compound heterozygous BRAT1 mutations [c.1564G > A (p.Glu522Lys) and c.638dup (p.Val214Glyfs*189)]. Homozygous and compound heterozygous BRAT1 mutations have been described in patients with lethal neonatal rigidity and multifocal seizure syndrome (MIM# 614498). The seven previously described patients suffered from uncontrolled seizures, and all of those patients died in their first months of life. BRAT1 acts as a regulator of cellular proliferation and migration and is required for mitochondrial function. The loss of these functions may explain the cerebral atrophy observed in this case of PE. This case highlights the extraordinary potential of next generation technologies for the diagnosis of rare genetic diseases, including PE. Making a prompt diagnosis of PE is important for genetic counseling and disease management.
Asunto(s)
Microcefalia/genética , Mutación/genética , Proteínas Nucleares/genética , Convulsiones/genética , Niño , Heterocigoto , Humanos , MasculinoRESUMEN
Several lines of evidence suggest that the dopamine transporter gene (DAT1) plays a crucial role in attention deficit hyperactivity disorder (ADHD). Concretely, recent data indicate that the 10-repeat (10R) DAT1 allele may mediate neuropsychological functioning, response to methylphenidate, and even brain function and structure in children with ADHD. This study aimed to investigate the influence of 10R DAT1 on thickness of the prefrontal cortex in children and adolescents with ADHD. To this end, brain magnetic resonance images were acquired from 33 patients with homozygosity for the 10R allele and 30 patients with a single copy or no copy of the allele. The prefrontal cortex of each MRI scan was automatically parceled into regions of interest (ROIs) based on Brodmann areas (BA). The two groups were matched for age, gender, IQ, ADHD subtype, symptom severity, comorbidity and medication status. However, patients with two copies of the 10R allele exhibited significantly decreased cortical thickness in right BA 46 relative to patients with one or fewer copies of the allele. No other prefrontal ROI differed significantly between the two groups. Present findings suggest that cortical thickness of right lateral prefrontal cortex (BA 46) is influenced by the presence of the DAT1 10 repeat allele in children and adolescents with ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/diagnóstico , Trastorno por Déficit de Atención con Hiperactividad/genética , Proteínas de Transporte de Dopamina a través de la Membrana Plasmática/genética , Genotipo , Corteza Prefrontal/patología , Adolescente , Alelos , Trastorno por Déficit de Atención con Hiperactividad/psicología , Corteza Cerebral/patología , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Tamaño de los ÓrganosRESUMEN
Structural and functional brain studies on attention deficit/hyperactivity disorder (ADHD) have primarily examined anatomical abnormalities in the prefronto-striatal circuitry (especially, dorsal and lateral areas of the prefrontal cortex and dorsal striatum). There is, however, increased evidence that several temporal lobe regions could play an important role in ADHD. The present study used MRI-based measurements of cortical thickness to examine possible differences in both prefrontal and temporal lobe regions between medication-näive patients with ADHD (N = 50) and age- and sex-matched typically developing controls (N = 50). Subjects with ADHD exhibited significantly decreased cortical thickness in the right temporal pole and orbitofrontal cortex (OFC) relative to healthy comparison subjects. These differences remained significant after controlling for confounding effects of age, overall mean cortical thickness and comorbid externalizing conditions, such as oppositional defiant and conduct disorders. These results point to the involvement of the temporal pole and OFC in the neuropathology of ADHD. Moreover, present findings add evidence to the assumption that multiple brain regions and psychological processes are associated with ADHD.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad/patología , Trastorno de la Conducta/patología , Cuerpo Estriado/patología , Imagen por Resonancia Magnética , Corteza Prefrontal/patología , Lóbulo Temporal/patología , Adolescente , Encéfalo/patología , Niño , Femenino , Humanos , MasculinoRESUMEN
CASE REPORT: We describe an unusual clinical case with an 11-Mb deletion at 4q27 (chr4: 123094652-134164491), craniosynostosis (CS), mild psychomotor retardation, and facial dysmorphic features. This deletion involves 18 genes; FGF2, NUDT6, and SPRY1 are primarily or secondarily implicated in human cranial bone and sagittal suture development and could play an important role in CS. CONCLUSIONS: Clinicians should always contemplate genetic studies in patients with syndromic CS. Mutational targeted genetic testing is appropriate for patients with classical or specific CS syndrome. Nevertheless, array comparative genomic hybridization (array CGH) should be considered as a first-line test in nontypical syndromic CS phenotype. Cytogenetic studies are decisive for genetic counseling indeed.
Asunto(s)
Anomalías Múltiples/genética , Deleción Cromosómica , Cromosomas Humanos Par 4/genética , Craneosinostosis/genética , Discapacidad Intelectual/genética , Atrofia Muscular/genética , Trastornos Psicomotores/genética , Niño , Anomalías Craneofaciales , Facies , Retardo del Crecimiento Fetal/genética , Factor 2 de Crecimiento de Fibroblastos/genética , Estudios de Asociación Genética , Asesoramiento Genético , Predisposición Genética a la Enfermedad/genética , Genotipo , Humanos , Masculino , Proteínas de la Membrana/genética , Fosfoproteínas/genética , Proteínas/genéticaRESUMEN
LBX1 plays a cardinal role in neuronal and muscular development in animal models. Its function in humans is unknown; it has been reported as a candidate gene for idiopathic scoliosis. Our goal is to document the first clinical case of a microduplication at 10q24.31 (chr10:102927883-103053612, hg19), affecting exclusively LBX1. The patient, a 12-year-old girl, showed attention problems, dyspraxia, idiopathic congenital scoliosis, and marked hypotrophy of paravertebral muscles. Her paternal aunt had a severe and progressive myopathy with a genetic study that revealed the same duplication. We propose to consider genetic studies, particularly of LBX1, in patients with scoliosis and/or hypotrophy-hypoplasia of paravertebral muscles of unknown etiology.
Asunto(s)
Duplicación Cromosómica , Cromosomas Humanos Par 10 , Enfermedades Musculares/genética , Escoliosis/genética , Niño , Hibridación Genómica Comparativa , Femenino , Estudios de Asociación Genética , Proteínas de Homeodominio/genética , Humanos , Imagen por Resonancia Magnética , Enfermedades Musculares/diagnóstico , Fenotipo , Radiografía , Escoliosis/diagnóstico , España , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Factores de Transcripción/genéticaRESUMEN
Interstitial microduplication of 3q29 has been recently described. Individuals with this syndrome have widely variable phenotypes. We describe the first clinical case with a 1.607 Mb duplication at 3q29 (chr3: 195,731,956-197,339,329), accompanied by severe intellectual disability, epilepsy, and cerebral palsy. This duplication involves 22 genes; PAK2, DLG1, BDH1, and FBXO45 are implicated in neuronal development and synaptic function and could play an important role in this syndrome. We propose considering genetic studies, particularly array comparative genomic hybridization, in patients with epilepsy and/or cerebral palsy of unknown etiology when dysmorphic features are present.
Asunto(s)
Parálisis Cerebral/genética , Trastornos de los Cromosomas/diagnóstico , Trastornos de los Cromosomas/genética , Duplicación Cromosómica/genética , Epilepsia/genética , Discapacidad Intelectual/genética , Fenotipo , Encéfalo/patología , Parálisis Cerebral/diagnóstico , Niño , Hibridación Genómica Comparativa , Epilepsia/diagnóstico , Femenino , Humanos , Discapacidad Intelectual/diagnóstico , Imagen por Resonancia MagnéticaRESUMEN
BACKGROUND: Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with a low incidence in the paediatric population; cortical atrophy is often striking, even in the early stages of the disease. Evidence of cortical thinning in childhood MS is scant. AIMS: This study aimed to assess cortical thickness in paediatric patients during the initial attack of remitting-relapsing MS. METHODS: We report two cases of remitting-relapsing MS, with initial attacks at 12 and 16 years of age. We analysed brain cortical thickness (CTh) in these patients and compared these data to the CTh of a control group comprised of six 12-year-old females and six 16-year-old males. RESULTS: Both cases exhibited a total brain CTh significantly below that of the control group. This difference was also observed when analysing the CTh of all lobes except the left parietal lobe in one of the cases. CONCLUSIONS: Cortical atrophy is already present at the time of onset of MS. Studies with larger patient populations that have a more homogenous clinical presentation could identify the time of onset of cortical atrophy and use this parameter as a prognostic and/or treatment marker of MS.
