Ulnar ray a/hypoplasia: evidence for a developmental field defect on the basis of genetic heterogeneity. Report of three Brazilian families.

We report on five Brazilian patients from three unrelated families with congenital anomalies of the upper limbs. Ulnar aplasia/hypoplasia was the main reason for examining these patients. Evidence for existence of an ulnar developmental field is based on genetic heterogeneity. Clinical and genetic aspects of the ulnar ray defects are discussed.

Developmental and behavioral effects of postnatal amitraz exposure in rats

The effects of postnatal amitraz exposure on physical and behavioral parameters were studied in Wistar rats, whose lactating dams received the pesticide (10 mg/Kg) orally on days 1, 4, 7, 10, 13, 16 and 19 of lactation; control dams received distilled water (1 ml/kg) on the same days. A total of 18 different litters (9 of them control and 9 experimental) born after a 21- day gestation were used. The results showed that the median effective time (ET50) for fur development, eye opening, testis descent and onset of the startle response were increased in rats postnatally exposed to amitraz (2.7, 15.1, 21.6 and 15.3 days, respectively) compared to those of the control pups (1.8, 14.0, 19.9 and 12.9 days, respectively). The ages of incisor eruption, total unfolding of the external ears, vaginal and ear opening and the time taken to perform the grasping hindlimb reflex were not affected by amitraz exposure. Pups from dams treated with amitraz during lactation took more time (in seconds) to perform the surface righting reflex on postnatal days (PND) 3 (25.0 ±2.0), 4 (12.3 ± 1.2) and 5 (8.7 ± 0.9) in relation to controls (10.6 ± 1.2; 4.5 ± 0.6 and 3.4 ± 0.4, respectively); the climbing response was not changed by amitraz. Postnatal amitraz exposure increased spontaneous motor activity of male and female pups in the open-field on PND 16 (140± 11)and 17(124± 12), and 16 (104±9), 17 (137 ± 9) and 18 (106 ± 8), respectively. Data on spontaneous motor activity of the control male and female pups were 59 ± 11 and 69 ± 10 for days 16 and 17 and 49 ± 9, 48 ± 7 and 56 ± 7 for days 16, 17 and 18, respectively. Some qualitative differences were also observed in spontaneous motor behavior; thus, raising the head, shoulder and pelvis matured one or two days later in the amitraz- treated offspring. Postnatal amitraz exposure did not change locomotion and rearing frequencies or immobility time in the open-field on PND 30, 60 and 90. The present findings indicate that postnatal exposure to amitraz caused transient developmental and behavioral changes in the exposed offspring and suggest that further investigation of the potential health risk of amitraz exposure to developing human and animal offsprings may be warranted.

Molecular and Cytogenetic Analyses on Brazilian Youths with Pervasive Developmental Disorders

The Pervasive Developmental Disorders (PDDs) constitute a group of behavioral and neurobiological impairment conditions whose main features are delayed communicative and cognitive development. Genetic factors are reportedly associated with PDDs and particular genetic abnormalities are frequently found in specific diagnostic subgroups such as the autism spectrum disorders. This study evaluated cytogenetic and molecular parameters in 30 youths with autism or other PDDs. The fragile X syndrome was the most common genetic abnormality detected, presented by 1 patient with autism and 1 patient with PPD not-otherwise specified (PPD-NOS). One girl with PDD-NOS was found to have tetrasomy for the 15q11-q13 region, and one patient with autism exhibited in 2/100 metaphases an inv(7)(p15q36), thus suggesting a mosaicism 46,XX/46,XX,inv(7)(p15q36) or representing a coincidental finding. The high frequency of chromosomopathies support the hypothesis that PDDs may develop as a consequence to chromosomal abnormalities and justify the cytogenetic and molecular assessment in all patients with PDDs for establishment of diagnosis.

Growth and developmental outcomes of the extremely preterm infant

Objetive: To provide information for pediatricians and neonatologists to create realistic outcome expectations and thus help plan their actions. Sources of data: Searches were made of the Cochrane Library, MEDLINE, and Lilacs databases. Summary of the findings: The assessment of growth and development over the first 2-3 years must adjust chronological age with respect of the degree of prematurity. There is special concern regarding the prognoses of small for gestational age preterm infants, and for those with bronchopulmonary dysplasia. Attention must be directed towards improving the nutrition of extremely low birth weight infants during their first years of life; these infants have high prevalence levels of failure to catch-up on growth, diseases and rehospitalizations during their first 2 years. They are frequently underweight and shorter than expected during early childhood, but delayed catch-up growth may occur between 8 and 14 years. Extremely low birth weight infants are at increased risk of neurological abnormalities and developmental delays during their first years of life. Educational, psychological, and behavioral problems are frequent during school years. Teenage and adult outcomes show that although some performance differences persist, social integration is not impaired. Conclusions: The growth and neurodevelopment of all ELBW infants must be carefully monitored after discharge, to ensure that children and their families receive adequate support and intervention to optimize prognoses. Copyright © 2005 by Sociedade Brasileira de Pediatria.

Treatment of developmental defect of upper lip with carbon dioxide laser radiation (CO2): First surgical time

With the exception of the cleft lip, developmental defects (DD) of the lip are rare. The upper lip originates from the ectomesenchyme and is formed by the merging of the nasal medial and lateral processes with the maxillary process. Disturbances during this formation period can cause DD with functional and/or esthetic repercussions. We present a case of DD of the upper lip in a patient with a history of progressive growth of the left lateral portion of the upper lip that occurred from the time of birth until the age of 22 years. Clinical examination revealed hypertrophy of the area from the left philtral columns to the left commissure of the lip, extending the portion of the surface mucosa creating a flaccid and asymptomatic tissue mass. All other buccal structures appeared to be within normal limits and without any evidence of defects or deformities. In the surgical planning we decided to carry out corrective surgery in two phases. The first phase accomplished a conservative excision of the total abnormal labial tissue mass with a CO2 laser radiation (5 W in continuous mode, bunch diameter φ = 0.6 mm with a power density of 768 W/cm2 and fluency of 0.231 J/cm2) being careful to preserve the vermilion portion of the lip. Postsurgical clinical evaluations were done every three days until the skin sutures were removed and then every seven days until two months post surgery. While the entire mass of excessive tissue could not be completely removed, the removal of the excessive mucosal tissue produced a very good outcome relative to lip function, with a good esthetic result without scarring, and good tissue mobility. The results showed that the CO2 laser is an extremely useful instrument that can provide excellent control of the surgical field and allow for healing that produces excellent functional and esthetic results. © 2005 Taylor & Francis.

Phonological remediation program in students with developmental dyslexia

Background: program for phonological remediation in developmental dyslexia. Aim: to verify the efficacy of a program for phonological remediation in students with developmental dyslexia. Specific goals of this study involved the comparison of the linguistic-cognitive performance of students with developmental dyslexia with that of students considered good readers; to compare the results obtained in pre and post-testing situations of students with dyslexia who were and were not submitted to the program; and to compare the results obtained with the phonological remediation program in students with developmental dyslexia to those obtained in good readers. Method: participants of this study were 24 students who were divided as follows: Group I (GI) was divided in two other groups - Gle with 6 students with developmental dyslexia who were submitted to the program; and Glc with 6 students with developmental dyslexia who were not submitted to the program; Group II (GII) was also divided in two other groups - GIIe with 6 good readers who were submitted to the program, and GIIc with 6 good readers who were not submitted to the program. The phonological remediation program (Gonzalez & Rosquete, 2002) was developed in three stages: pre-testing, training and post-testing. Results: results indicate that GI presented a lower performance in phonological skills, reading and writing when compared to GII in the pre-testing situation. However, GIe presented a similar performance to that of GII in the post-testing situation, indicating the effectiveness of the phonological remediation program in students with developmental dyslexia. Conclusion: this study made evident the effectiveness of the phonological remediation program in students with developmental dyslexia.

Developmental Disturbance of an Unerupted permanent incisor due to trauma to its predecessor

Developmental disturbances of permanent teeth can result from trauma to primary teeth because of the proximity of the root of the primary teeth to their permanent successors. We describe the case of a 14-month-old boy who was referred to the baby clinic of the School of Dentistry, Universidad Estadual Paulista, Araçatuba, Brazil, after sustaining a severe trauma that led to intrusion of the right primary central incisor. Radiographic examination 4 years after the trauma showed a developing morphological change in the germ of the permanent successor. On eruption of the permanent central incisor, a crown malformation along with enamel hypoplasia was observed. We concludethat radiographic follow-up is indicated after trauma to monitor possible sequelae in the permanent successors even before their eruption. © 2011 Canadian Dental Association.

Chromosomal imbalances in successive moments of human bladder urothelial carcinoma

Objective: To understand developmental characteristics of urinary bladder carcinomas (UBC) by evaluating genomic alterations and p53 protein expression in primary tumors, their recurrences, and in the morphologically normal urothelium of UBC patients. Methods: Tumors and their respective recurrences, six low-grade and five high-grade cases, provided 19 samples that were submitted to laser microdissection capture followed by high resolution comparative genomic hybridization (HR-CGH). HR-CGH profiles went through two different analyses-all tumors combined or classified according to their respective histologic grades. In a supplementary analysis, 124 primary urothelial tumors, their recurrences, and normal urothelium biopsied during the period between tumor surgical resection and recurrence, were submitted to immunohistochemical analyses of the p53 protein. During the follow-up of at least 21 patients, urinary bladder washes citologically negative for neoplastic cells were submitted to fluorescence in situ hybridization (FISH) to detect copy number alterations in centromeres 7, 17, and 9p21 region. Results and Conclusions: HR-CGH indicated high frequencies (80%) of gains in 11p12 and losses in 16p12, in line with suggestions that these chromosome regions contain genes critical for urinary bladder carcinogenesis. Within a same patient, tumors and their respective recurrences showed common genomic losses and gains, which implies that the genomic profile acquired by primary tumors was relatively stable. There were exclusive genomic alterations in low and in high grade tumors. Genes mapped in these regions should be investigated on their involvement in the urinary bladder carcinogenesis. Successive tumors from same patient did not present similar levels of protein p53 expression; however, when cases were grouped according to tumor histologic grades, p53 expression was directly proportional to tumor grades. Biopsies taken during the follow-up of patients with history of previously resected UBC revealed that 5/15 patients with no histologic alterations had more than 25% of urothelial cells expressing the p53 protein, suggesting that the apparently normal urothelium was genomically unstable. No numerical alterations of the chromosomes 7, 17, and 9p21 region were found by FISH during the periods free-of-neoplasia. Our data are informative for further studies to better understand urinary bladder urothelial carcinogenesis. © 2013 Elsevier Inc.

Motor development of infants exposed to maternal human immunodeficiency virus (HIV) but not infected

Background: To assess the motor development of infants exposed to maternal human immunodeficiency virus (HIV). Methods: Thirty infants were assessed in the period from November 2009 to March 2010 at the AIDS Reference and Training Centre, in São Paulo, Brazil. The assessment instrument used in the research was the Alberta Infant Motor Scale (AIMS). All 30 infants used the antiretroviral drug properly for 42 consecutive days, in accordance with the protocol of the World Health Organization. Results: Out of the total number of infants, 27 (90%) had proper motor performance and 3 (10%) presented motor delay, according to the AIMS. Discussion: This study demonstrated that only 10% of the assessed group had developmental delay and no relation with environmental variables was detected, such as maternal level of education, social and economic issues, maternal practices, attendance at the day care center, and drug use during pregnancy. It is important to emphasize the necessity of studies with a larger number of participants.

A study of the role of the FOXP2 and CNTNAP2 genes in persistent developmental stuttering

A number of speech disorders including stuttering have been shown to have important genetic contributions, as indicated by high heritability estimates from twin and other studies. We studied the potential contribution to stuttering from variants in the FOXP2 gene, which have previously been associated with developmental verbal dyspraxia, and from variants in the CNTNAP2 gene, which have been associated with specific language impairment (SLI). DNA sequence analysis of these two genes in a group of 602 unrelated cases, all with familial persistent developmental stuttering, revealed no excess of potentially deleterious coding sequence variants in the cases compared to a matched group of 487 well characterized neurologically normal controls. This was compared to the distribution of variants in the GNPTAB, GNPTG, and NAGPA genes which have previously been associated with persistent stuttering. Using an expanded subject data set, we again found that NAGPA showed significantly different mutation frequencies in North Americans of European descent (p = 0.0091) and a significant difference existed in the mutation frequency of GNPTAB in Brazilians (p = 0.00050). No significant differences in mutation frequency in the FOXP2 and CNTNAP2 genes were observed between cases and controls. To examine the pattern of expression of these five genes in the human brain, real time quantitative reverse transcription PCR was performed on RNA purified from 27 different human brain regions. The expression patterns of FOXP2 and CNTNAP2 were generally different from those of GNPTAB, GNPTG and NAPGA in terms of relatively lower expression in the cerebellum. This study provides an improved estimate of the contribution of mutations in GNPTAB, GNPTG and NAGPA to persistent stuttering, and suggests that variants in FOXP2 and CNTNAP2 are not involved in the genesis of familial persistent stuttering. This, together with the different brain expression patterns of GNPTAB, GNPTG, and NAGPA compared to that of FOXP2 and CNTNAP2, suggests that the genetic neuropathological origins of stuttering differ from those of verbal dyspraxia and SLI. Published by Elsevier Inc.

Early influence of auditory stimuli on upper-limb movements in young human infants: an overview

Given that the auditory system is rather well developed at the end of the third trimester of pregnancy, it is likely that couplings between acoustics and motor activity can be integrated as early as at the beginning of postnatal life. The aim of the present mini-review was to summarize and discuss studies on early auditory-motor integration, focusing particularly on upper-limb movements (one of the most crucial means to interact with the environment) in association with auditory stimuli, to develop further understanding of their significance with regard to early infant development. Many studies have investigated the relationship between various infant behaviors (e.g., sucking, visual fixation, head turning) and auditory stimuli, and established that human infants can be observed displaying couplings between action and environmental sensory stimulation already from just after birth, clearly indicating a propensity for intentional behavior. Surprisingly few studies, however, have investigated the associations between upper-limb movements and different auditory stimuli in newborns and young infants, infants born at risk for developmental disorders/delays in particular. Findings from studies of early auditory-motor interaction support that the developing integration of sensory and motor systems is a fundamental part of the process guiding the development of goal-directed action in infancy, of great importance for continued motor, perceptual, and cognitive development. At-risk infants (e.g., those born preterm) may display increasing central auditory processing disorders, negatively affecting early sensorymotor integration, and resulting in long-term consequences on gesturing, language development, and social communication. Consequently, there is a need for more studies on such implications.

DEVELOPMENTAL STATUS OF N-(3-CHLORO-4-METHYLPHENYL) ACETAMIDE AS A CANDIDATE BLACKBIRD/STARLING ROOST TOXICANT

Large winter roosts of blackbirds (Icteridae) and starlings (Sturnus vulgaris) often cause conflicts, both real and imagined, between the birds and local human popula- tions. These conflicts may range from objections to the noise and odor engendered by thousands or millions of birds, to fear of epidemic human and livestock diseases, and the possibility of economic losses from crop depredations. Many people believe the most direct way to combat these conflicts is to reduce local roosting populations by kill- ing the birds. In response to this perceived need for a roost toxicant, the U.S. Fish and Wildlife Service (FWS) developed PA-14, a surfactant which can be aerially applied to problem roosts for population reduction (Lefebvre and Seubert 1970). Successful use of this material, however, requires concurrent rainfall and low temperatures, conditions which may not occur sufficiently often to permit roost treatment at desired times or places. Because of this difficulty, and continued pressures from management person- nel and the agricultural community, the Service has continued its search for a safe, ef- fective roost toxicant usable without severe weather restrictions. One of the current candidate materials is N-(3-chloro-4-methylphenyl)acetamide (CAT, DRC-2698), a derivative of StarlicideR (DRC-1339). This compound was initially developed by S.A. Peoples of the University of California-Davis (Peoples et al. 1976). California researchers are still investigating the avicidal potential of CAT, mainly on baits and in wick perches, while FWS interest has centered thus far on its possible utility as an aerially applied roost treatment. This report is a summary of our investigations to date.

Cytogenomic characterization of an unexpected 17.6 Mb 9p deletion associated to a 14.8 Mb 20p duplication in a dysmorphic patient with multiple congenital anomalies presenting a normal G-banding karyotype

We describe a female patient with developmental delay, dysmorphic features and multiple congenital anomalies who presented a normal G-banded karyotype at the 550-band resolution. Array and multiplex-ligation probe amplification (MLPA) techniques identified an unexpected large unbalanced genomic aberration: a 17.6 Mb deletion of 9p associated to a 14.8 Mb duplication of 20p. The deleted 9p genes, especially CER1 and FREM1, seem to be more relevant to the phenotype than the duplicated 20p genes. This study also shows the relevance of using molecular techniques to make an accurate diagnosis in patients with dysmorphic features and multiple anomalies suggestive of chromosome aberration, even if on G-banding their karyotype appears to be normal. Fluorescence in situ hybridization (FISH) was necessary to identify a masked balanced translocation in the patient's mother, indicating the importance of associating cytogenetic and molecular techniques in clinical genetics, given the implications for patient management and genetic counseling. (C) 2012 Elsevier B.V. All rights reserved.