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). © 2016 Wiley Periodicals, Inc.

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.

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.

Habilidades sociais em pacientes com sindrome velocardiofacial / Social skills in patients with velocardiofacial Syndrome

A síndrome Velocardiofacial (SVCF) é também conhecida como síndrome de deleção 22q11.2, como uma condição genética associada com uma expressão multisistêmica incluindo: mudanças faciais, desordens neurológicas, déficits cardíacos, fissura submucosa de palato, dificuldades de fala e linguagem, prevalência de TDAH e aumento do risco de problemas psiquiátricos e comportamentais. Objetivo: o objetivo deste estudo foi avaliar o repertório de habilidades socias em 12 individuos com diagnóstico de sindrome velocardiofacial sendo oito mulheres e quatro homens com idades entre 17 e 25 anos em diferentes situações(trabalho, escola, família) para estimar a possibilidade do impacto destas dificuldades no seu repertório social. Método: A coleta de dados incluiu análise de prontuário e o Inventário de Habilidades Sociais com 38 questões. Resultados: Os resultados mostraram sete sujeitos com indicação de treinamento para habilidades sociais e cinco com repertório normal. Entretanto, na análise fatorial dos escores, quatro destes cinco sujeitos mostraram ao menos um déficit de habilidade, sendo o fator 3 (conversação e inibição social) e o fator 4 (autoexpressão e exposição a novas situações) mais freqüentes seguidos pelo fator 1 (enfrentamento e auto-afirmação). Outra analise indicou que a dificuldade mais freqüente relatada foi quanto a capacidade de recusar pedido abusivo ou expressar desacordo com os amigos. Conclusão: As habilidades sociais são importantes por fazerem parte da SVCF e ainda sugerem um programa de treinamento social das habilidades sociais nestes pacientes.

Velocardiofacial syndrome (VCFS), also known as 22q11.2 deletion syndrome, is a common genetic condition associated with a multisystemic expression, which includes facial features, neurodevelopmental disabilities, cardiac defects, submucosal cleft palate, speech and language difficulties, learning disabilities, prevalence of Attention Deficit Hyperactivity disorder (ADHD), and increased risk for developing behavior and psychiatric disorders. Objective: The purpose of this study was to characterize the social skills of twelve subjects – eight female and four male – with VCFS at 75 years old, in different situations (work, school, family) to estimate the possibility of impact of these difficulties in social repertory. Methods: Data collection included handbook analysis and Social Skills Inventory with 38 multiple-choice questions. Results: The results showed seven subjects with indication for social skills training and five with normal range of social skills. However, in the factorial analysis of the scores, four out of five subjects showed at least one specific skill impairment, factor 3 (conversation and social nimbleness) and factor 4 (self-expression and new situations) being the most frequent factors followed by factor 1 (coping and self-affirmation). Another analysis indicated that one of the most frequent difficulties was related to the capacity to refuse an abusive order and to express unpleasantness to the friends. Conclusions: Important social disabilities can be part of VCFS phenotype and, in such a way that the spreading of these findings can contribute to design a social skills training program to these patients.

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.

Evolução de habilidades comunicativas na Síndrome de Williams: processo terapêutico de um caso clínico / Communicative abilities progress in Williams syndrome: therapeutic process in a clinical report

Introdução: a Síndrome de Williams, uma rara síndrome genética de herança autossômica dominante, exerce impacto sobre diversas áreas do desenvolvimento, incluindo as áreas cognitiva, lingüística, comportamental e motora, com probabilidade de ocorrência de 1:20.000 crianças (Sugayama et al., 2000). O objetivo do presente estudo foi caracterizar a evolução das habilidades comunicativas, bem como descrever o processo de intervenção fonoaudiológica de um indivíduo com Síndrome de Williams. Método: criança do gênero feminino acompanhada em terapia fonoaudiológica desde os cinco anos de idade, durante nove meses. Para análise dos resultados foram consideradas as avaliações inicial e final, que englobaram procedimentos clínicos e formais, além de observações terapêuticas. Resultados: observou-se evolução na brincadeira simbólica; nos aspectos pragmático, sintático, semântico e fonético-fonológico; nos comportamentos adaptativos, motor grosseiro, motor delicado, pessoal-social e lingüístico; nas habilidades de recepção auditiva e visual, closura visual e gramatical, associação visual e auditiva e expressão manual. Verificou-se, após o período de intervenção, desenvolvimento comunicativo lento, porém constante. Conclusão: este estudo de caso evidenciou aspectos importantes a serem considerados no que se refere à avaliação e intervenção de indivíduos com a Síndrome de Williams, o que é precário na literatura pertinente