Dagma Venturini Marques Abramides

Specific language impairment: linguistic and neurobiological aspects

Specific language impairment (SLI) occurs when children present language maturation, at least 12 months behind their chronological age in the absence of sensory or intellectual deficits, pervasive developmental disorders, evident cerebral damage, and adequate social and emotional conditions. The aim of this study was to classify a group of children according to the subtypes of SLI and to correlate clinical manifestations with cortical abnormalities. Seventeen children with SLI were evaluated. Language assessment was based on standardized test (Peabody) and a non-standardized protocol, which included phonological, syntactical, semantical, pragmatical and lexical aspects of language. All children, except one, had abnormal MRI. Thirteen children presented perisylvian polymicrogyria. The MRI findings in the remaining three patients were: right frontal polymicrogyria, bilateral fronto-parietal atrophy, and hypogenesis of corpus callosum with Chiari I. The data show that patients with posterior cortical involvement tended to present milder form of SLI (no sign of articulatory or bucofacial praxis disturbance), while diffuse polymicrogyric perisylvian cortex usually was seen in patients who presented severe clinical manifestation, mainly phonological-syntactic deficit. In conclusion, SLI may be associated with perisylvian polymicrogyria and clinical manifestation may vary according to the extent of cortical anomaly.

Identification of a Microdeletion at the 7q33-q35 Disrupting the CNTNAP2 Gene in a Brazilian Stuttering Case

Speech and language disorders are some of the most common referral reasons to child development centers accounting for approximately 40% of cases. Stuttering is a disorder in which involuntary repetition, prolongation, or cessation of the sound precludes the flow of speech. About 5% of individuals in the general population have a stuttering problem, and about 80% of the affected children recover naturally. The causal factors of stuttering remain uncertain in most cases; studies suggest that genetic factors are responsible for 70% of the variance in liability for stuttering, whereas the remaining 30% is due to environmental effects supporting a complex cause of the disorder. The use of high‐resolution genome wide array comparative genomic hybridization has proven to be a powerful strategy to narrow down candidate regions for complex disorders. We report on a case with a complex set of speech and language difficulties including stuttering who presented with a 10 Mb deletion of chromosome region 7q33‐35 causing the deletion of several genes and the disruption of CNTNAP2 by deleting the first three exons of the gene. CNTNAP2 is known to be involved in the cause of language and speech disorders and autism spectrum disorder and is in the same pathway as FOXP2, another important language gene, which makes it a candidate gene for causal studies speech and language disorders such as stuttering.

Apert syndrome: factors involved in the cognitive development.

Apert syndrome is characterized by craniosynostosis, symmetric syndactyly and other systemic malformations, with mental retardation usually present. The objective of this study was to correlate brain malformations and timing for surgery with neuropsychological evaluation. We also tried to determine other relevant aspects involved in cognitive development of these patients such as social classification of families and parents education. Eighteen patients with Apert syndrome were studied, whose ages were between 14 and 322 months. Brain abnormalities were observed in 55.6% of them. The intelligence quotient or developmental quotient values observed were between 45 and 108. Mental development was related to the quality of family environment and parents education. Mental development was not correlated to brain malformation or age at time of operation. In conclusion, quality of family environment was the most significant factor directly involved in mental development of patients with Apert syndrome.

Typical phenotypic spectrum of velocardiofacial syndrome occurs independently of deletion size in chromosome 22q11.2

Velocardiofacial syndrome (VCFS) is a relatively common developmental disorder characterized by craniofacial anomalies and conotruncal heart defects. Many VCFS patients present hemizygous deletions on part of chromosome 22q11.2; suggestive that haploinsufficiency in this region is responsible for this etiology. Most 22q11.2 deletions occur sporadically, although in some cases the deletion may be transmitted. A total of 29 VCFS patients and their parents were genotyped using six consecutive polymorphic markers (STS) of the chromosome 22q11.2: D22S420, D22S941, D22S264, D22S306, D22S425, and D22S257. The results revealed that 72% (21/29) of the patients harbored a deletion involving the polymorphic markers D22S420, D22S941, and/or D22S264. Haplotype analysis showed that among the patients studied, the deletions were either of maternal or paternal origin. Our findings demonstrated that independently of their size, any deletion occurring in the VCFS critical region is enough to confer the patient phenotype.

Apert and Crouzon syndromes—cognitive development, brain abnormalities, and molecular aspects

Apert and Crouzon are the most common craniosynostosis syndromes associated with mutations in the fibroblast growth factor receptor 2 (FGFR2) gene. We conducted a study to examine the molecular biology, brain abnormalities, and cognitive development of individuals with these syndromes. A retrospective longitudinal review of 14 patients with Apert and Crouzon syndromes seen at the outpatient Craniofacial Surgery Hospital for Rehabilitation of Craniofacial Anomalies in Brazil from January 1999 through August 2010 was performed. Patients between 11 and 36 years of age (mean 18.29 ± 5.80), received cognitive evaluations, cerebral magnetic resonance imaging, and molecular DNA analyses. Eight patients with Apert syndrome (AS) had full scale intelligence quotients (FSIQs) that ranged from 47 to 108 (mean 76.9 ± 20.2), and structural brain abnormalities were identified in five of eight patients. Six patients presented with a gain‐of‐function mutation (p.Ser252Trp) in FGFR2 and FSIQs in those patients ranged from 47 to78 (mean 67.2 ± 10.7). One patient with a gain‐of‐function mutation (p.Pro253Arg) had a FSIQ of 108 and another patient with an atypical splice mutation (940–2A →G) had a FSIQ of 104. Six patients with Crouzon syndrome had with mutations in exons IIIa and IIIc of FGFR2 and their FSIQs ranged from 82 to 102 (mean 93.5 ± 6.7). These reveal that molecular aspects are another factor that can be considered in studies of global and cognitive development of patients with Apert and Crouzon syndrome (CS).

Language Skills and Neuropsychological Performance in Patients With SHH Mutations and a Holoprosencephaly-Like Phenotype

Here, we evaluate linguistic skills and neuropsychological performance in a sample of patients with SHH mutations and a holoprosencephaly (HPE)‐like phenotype, a minor form of classic HPE. Our findings suggest that patients with SHH mutations and a HPE‐like phenotype have normal cognitive ratios and significant language impairment. Imaging evaluation by magnetic resonance imaging (MRI) was normal in three patients and in one there was hypoplasia of the anterior commissure and the presence of a temporal cyst, apparently not related to the clinical findings.

Avaliação dos aspectos neuropsicolingüísticos de um caso de holoprosencefalia com mutação do gene SHH

The holoprosencephaly (HPE) is the most frequent of the craniofacial malformations described in literature. Several genes have already been identified as responsible for this kind of anomaly, among them, the Sonic Hedgehog (SHH), ZIC2, SIX3 and TGIF. The aim of this study was to evaluate the neuropsycholinguistic abilities of an individual with the HPE and mutation of the SHH gene, presenting phenotypic characteristics of the Like type. The results evidenced that, in spite of the lightness of the degree of HPE (Like phenopype), the patient showed significant loss of the linguistic abilities, although the cognitive aspects were adequate. The magnetic resonance of the encephalon revealed hypoplasia of the anterior commissure and presence of a temporal cyst on the left side, findings apparently not related to the clinic symptomatology.

Avaliação do grau de inteligibilidade de fala de crianças com desvio fonológico: implicações nas habilidades sociais

OBJETIVO: analisar a relacao entre o grau de inteligibilidade de fala e as habilidades sociais de comunicacao em criancas com diagnostico de desvio fonologico. METODO:participaram deste estudo 10 criancas, diagnosticadas com desvio fonologico, com idade cronologica media de 7,28 anos, sendo tres do genero feminino e sete do masculino, que realizavam terapia de linguagem duas vezes por semana em uma clinica escola de uma cidade de medio porte do estado de Sao Paulo. As criancas foram submetidas a avaliacao da fonologia por meio do instrumento ABFW, sendo que a gravidade do desvio fonologico foi baseada no calculo do Percentual de Consoantes Corretas (PCC). E em seguida foram filmadas em situacoes estruturas de interacao de maneira tal a obter uma amostra de fala espontânea, para caracterizar o grau de inteligibilidade de fala (GIF), alem de observar presenca ou ausencia dos componentes das habilidades sociais de comunicacao (HSC). Para analisar a relacao entre GIF e HSC foi utilizado o coeficiente de Spearman. RESULTADOS:foi possivel caracterizar as classes de HSC que encontram-se deficitarias em criancas diagnosticas com desvio fonologico, alem de verificar uma relacao significante e positiva entre o GIF e o HSC, mostrando que quanto maior o GIF maior a dificuldades nas HSC. CONCLUSAO: o estudo verificou a relacao entre GIF e HSC, alem de identificar as classes de HSC que encontram-se deficitarias em criancas com diagnostico de desvio fonologico, favorecendo a elaboracao de instrumentos para avaliacao e intervencao, permitindo assim, um melhor planejamento para cada caso.

Saethre-Chotzen Syndrome, Pro136His TWIST Mutation, Hearing Loss, and External and Middle Ear Structural Anomalies: Report on a Brazilian Family

Objective To describe the clinical, speech, hearing, and imaging findings in three members of a Brazilian family with Saethre-Chotzen syndrome (SCS) who presented some unusual characteristics within the spectrum of the syndrome. Design Clinical evaluation was performed by a multidisciplinary team. Direct sequencing of the polymerase chain reaction–amplified coding region of the TWIST1 gene, routine and electrophysiological hearing evaluation, speech evaluation, and imaging studies through computed tomography (CT) scan and magnetic resonance imaging (MRI) were performed. Results TWIST1 gene analysis revealed a Pro136His mutation in all patients. Hearing evaluation showed peripherial and mixed hearing loss in two of the patients, one of them with severe unilateral microtia. Computed tomography scan showed structural middle ear anomalies, and MRI showed distortion of the skull contour as well as some of the brain structures. Conclusions We report a previously undescribed TWIST1 gene mutation in patients with SCS. There is evidence that indicates hearing loss (conductive and mixed) can be related both with middle ear (microtia, high jugular bulb, and enlarged vestibules) as well as with brain stem anomalies. Here we discuss the relationship between the gene mutation and the clinical, imaging, speech, and hearing findings.

Possible new syndrome: Left ventricular noncompaction, partial agenesis of the corpus callosum, and developmental delay in a Brazilian child.

We report on the clinical, neuropsychological and language characteristics of a boy with left ventricular noncompaction cardiomyopathy (LVNC), agenesis of the splenium of the corpus callosum, minor anomalies of face and limbs, mild mental retardation, and speech and language disabilities. The occurrence of pilomatricoma (calcifying epithelioma) may be part of the clinical spectrum or a fortuitous finding. Compared to other related conditions with LVNC suggests that this is a “new” unique pattern MCA/MR syndrome.