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PubMed1999

Delayed development of reflexes and hyperactive locomotion in the spontaneous mutant "waltzing" of the musk shrew, Suncus murinus.

The autosomal recessive mutation waltzing (wz), displaying abnormal circling and head-shaking behavior, has previously been reported in the musk shrew (Suncus murinus). Postnatal development of reflexes and locomotor patterns in an open arena were examined in wz/wz mutant shrews. The wz/wz shrews showed extreme developmental delays in surface-righting reflex and negative geotaxis until 10-16 days after birth, but both reflexes eventually recovered to the levels of +/wz normal. Nevertheless, the wz/wz adults exhibited bi-directional circling behavior 59 times, head-tossing behavior 22 times and horizontal head-shaking behavior 6 times more frequent than in the +/wz controls. Although the wz/wz adult shrews were extremely hyperactive with daily spontaneous locomotor activity exceeding 4-7 times control shrew activity, they appeared to have a normal circadian rhythm. This shrew mutant may therefore be useful as a model for hyperactivity syndromes in humans.

Animals↗
PubMed2007

Social communication profiles of children with autism spectrum disorders late in the second year of life.

This study examined social communication profiles from behavior samples videotaped between 18 and 24 months of age in three groups of children: 50 with autism spectrum disorders (ASD), 23 with developmental delays (DD), and 50 with typical development (TD). The ASD group scored significantly lower than the DD group on 5 social communication measures and the TD group on all 14 measures, indicating distinct profiles late in the second year. Understanding was the strongest predictor of developmental level and behavior regulation and inventory of gestures were the strongest predictors of autism symptoms at 3 years of age. The predictive relations suggest five pivotal skills late in the second year that have a cascading effect on outcomes of children with ASD.

Attention↗
PubMed2003

Mild fetal cerebral ventriculomegaly: diagnosis, clinical associations, and outcomes.

The normal fetal lateral ventricular diameter remains stable at 10 mm over gestation. Mild ventriculomegaly, defined as a lateral ventricular diameter of >or=10 mm but or=3 mm but <or=8 mm occurs bilaterally in 0.15-0.7% of fetuses and unilaterally in 0.07% of pregnancies. This finding is associated with an increased risk of fetal chromosomal abnormalities, congenital anomalies and infections, syndromes, perinatal death, and childhood developmental delays. Prenatal evaluation includes targeted sonographic examination for central nervous system and extra-central nervous system abnormalities, and diagnostic amniocentesis for chromosomal analysis and infectious disease studies. Individualized patient counseling is based on these test results. Optimal postnatal care involves appropriate pediatric neurologic and developmental specialists.

Cerebral Ventricles↗
PubMed1994

Cutaneous mucinosis of infancy.

Cutaneous mucinosis of infancy has been reported only rarely in the literature. We describe a case occurring in a black infant girl. Although no associated abnormalities have been described previously, our patient had a history of developmental delay, congenital cataracts, bilateral inguinal hernias, and an accessory tragus. The significance of these features is unclear.

Cataract↗
PubMed1987

Partial monosomy 12p13.1----13.3.

We describe a 27 month old female child with partial monosomy for the short arm of chromosome 12: 46,XX,del(12)(p13.1----p13.3). She differs from the eight cases described by others, in that she is less severely affected. Her main clinical features are developmental delay, protruding tongue, strabismus, slightly unusual facies, slight micrognathia, and speech delay.

Child, Preschool↗
PubMed1999

Comparison between creatine kinase brain isoenzyme (CKBB) activity and Sarnat score for prediction of adverse outcome following perinatal asphyxia.

AIM: To assess whether plasma creatine kinase brain isoenzyme (CKBB) levels or Sarnat scores are more accurate for prediction of poor neurological outcome in babies with suspected birth asphyxia. METHODS: In a retrospective study of 97 babies CKBB levels were compared to the presence of severe hypoxic ischaemic encephalopathy (HIE) as a predictive test for these outcomes: developmental delay, cerebral palsy, visual problems, deafness or death from perinatal asphyxia. The tests were compared using positive predictive values (PPV) and likelihood ratios (LR) with confidence intervals (CI). RESULTS: 3 babies had died from perinatal asphyxia and 14 survivors were found to have neurological or developmental problems. CKBB was elevated in babies with severe HIE (p = 0.0004). A receiver operator characteristic (ROC) curve showed the optimal discriminating value for CKBB to be 21 IU/L but the CKBB was a poor predictive test. For prediction of adverse outcome: CKBB > 21 sensitivity 76%, specificity 40%, PPV 21% and LR 1.3 (95% CI 0.8-1.7). Severe HIE sensitivity 53%, specificity 95%, PPV 69% and LR 10.6 (95% CI 3.8-29.2). CONCLUSION: CKBB is elevated following birth asphyxia but is a poor predictor of adverse neurological outcome.

Asphyxia Neonatorum↗
PubMed1990

Congenital hearing loss in Jervell and Lange-Nielsen syndrome.

Jervell and Lange-Nielsen syndrome is an autosomal recessive hereditary condition that presents with cardiac abnormalities characterized by a prolonged Q-T electrocardiographic pattern and congenital severe-to-profound auditory deficits. This paper describes the auditory history of twin boys born out of consanguinity and diagnosed with this syndrome. Both infants were products of the neonatal intensive care unit (NICU) and failed initial ABR screening. Diagnostic evaluation demonstrated profound hearing loss and developmental delays for each infant. Because sudden death is a consequence, audiologists are advised to recognize signs and symptoms associated with this syndrome.

Child, Preschool↗
PubMedDate not supplied

Human immunodeficiency virus within the brains of children with AIDS.

Infants and children with symptomatic human immunodeficiency virus (HIV) infection frequently develop neurologic disease with symptoms and signs of acquired microcephaly, developmental delays, encephalopathy, pyramidal tract signs, and less often, movement disorders and ataxia. However, clinical courses vary and, based upon progression of neurologic findings, we have classified them into 2 broad categories; progressive (loss of previously acquired language and cognitive skills) and plateau (failure to acquire additional developmental skills). We have used immunocytochemistry to localize HIV within the brains of neurologically involved children with AIDS. Interestingly, the brains of those children with a progressive neurologic course showed readily detectable HIV antigen, while those with a plateau course showed little or no detectable HIV. These findings suggest that in children with symptomatic HIV infection, the progressive neurologic deterioration is due to continued presence of HIV within deep white matter and gray matter, while the plateau neurologic course is due to HIV induced damage followed by either limited penetration of virus into the central nervous system, or clearance of virus below detectable limits.

AIDS Dementia Complex↗
PubMed1996

Outcome of children born to epileptic mothers treated with carbamazepine during pregnancy.

AIM: The purpose of the study was to assess whether there was an increased rate of congenital anomalies or significant developmental delay in infants of women with epilepsy who had been treated with carbamazepine during pregnancy. METHODS: 47 children were studied, aged 6 months-6 years, who were born to 37 epileptic mothers on carbamazepine monotherapy (group A). All children had a complete physical and neurodevelopmental assessment by a developmental paediatrician, and 41 a complete psychological evaluation. They were compared with 47 children of similar socioeconomic status (group B). RESULTS: Six of the 47 children in group A had typical facial features of 'carbamazepine syndrome'. The average cognitive score of children in group A was significantly lower than in group B. This was mainly because all six children with carbamazepine syndrome had a development quotient or intelligence quotient below 90. There were no differences between the two groups in physical growth or in the rate of major anomalies. Two children in group A had cleft palate but in each case this was found in a parent as well. CONCLUSIONS: In utero exposure to carbamazepine may result in 'carbamazepine syndrome' characterised by facial dysmorphic features and mild mental retardation. Prevalence of carbamazepine syndrome does not seem to be related to the dose of carbamazepine or the presence of maternal convulsions. It may depend upon heredofamilial factors that have yet to be defined. One possible factor is decreased activity of the enzyme epoxide hydrolase with resulting increased concentrations of carbamazepine epoxide which may be teratogenic.

Anticonvulsants↗
PubMed1997

A male with fetal valproate syndrome and autism.

Fetal valproate syndrome (FVS) is characterized by minor craniofacial anomalies, major organ malformations, and developmental delay. We report on a patient who has a clinical phenotype compatible with both FVS and autism. The presence of an autistic disorder in a previously reported case of FVS and similar findings in our patient suggest that a relation between this known teratogen and autism may exist.

Anticonvulsants↗
PubMed2005

Use of the bayley infant neurodevelopmental screener with premature infants.

OBJECTIVE: To examine the utility of the Bayley Infant Neurodevelopmental Screener (BINS) for the neurodevelopmental follow up of high-risk preterms. METHODS: The study group consisted of 122 preterm infants of the gestational ages between 26 and 37 weeks. Medical factors such as; mean birth weight, gestational age, gender, birth place and type, number of multiple pregnancy, days of hospitalization and oxygen therapy, use of antenatal steroids, and occurrence of sepsis for each patient were evaluated. The neurodevelopmental examination and BINS administration was made at each visit to the patients whose ages were adjusted for prematurity. RESULTS: At the corrected age of 7-10 months patients at 26-29 GA had significantly lower total means of BINS scores when compared to those of the other two groups at 30-32 and 33-37 GA (P<0.01 and P<0.001). At the corrected age of 3-4 months, the total means of the BINS scores of the patients at 30-32 GA were lower than that of the patients at 33-37 GA (P<0.009). at 7-10 months the scores of the items defining the expressive and cognitive functions of the patients at 26-29 GA were lower than those of the patients at 30-32 GA (P<0.05) and 33-37 GA (P<0.05). At 16-20 months the mean scores of the items of expressive functions were significantly lower in patients of the 26-29 GA compared to those of the patients of 33-37 GA (P<0.03). CONCLUSION: As data accumulates, BINS will turn out to be a quick way of determining infants at risk of developmental delay in many aspects of neurologically high risk conditions.

Age Factors↗
PubMed2005

Developmental outcome of epilepsy surgery in tuberous sclerosis complex.

In Tuberous sclerosis complex (TSC), neurological dysfunction, usually in association with epilepsy, is responsible for the greatest degree of disease-related disability. Epilepsy surgery is increasingly recognized as a therapeutic option given the often medication-resistant nature of the disease. Seven subjects with medically refractory epilepsy associated with TSC, who underwent surgery at a tertiary care epilepsy center and in whom both preoperative and postoperative neuropsychological data were available, were examined. The Vineland Adaptive Behavior Scales, and in one case, the WISC-III were utilized. Postoperatively, the composite standard scores declined in six of the seven subjects, although for the most part this decline was quite modest (8 points or less in 5/6 subjects). The mean overall developmental/intellectual quotients were comparable across assessments (preoperative M = 55, SD = 20.3; postoperative M = 49 SD = 16.6). Good outcomes appeared to be related to seizure relief. Age estimates of developmental level indicated developmental progress in the majority of subjects in the current sample, and may yield greater clinical information for individuals with developmental delay than do standard scores.

Adult↗
PubMedDate not supplied

Evaluation of the Denver Developmental Screening Test as applied to African children.

The Denver Developmental Screening Test (DDST) is a tool widely used by nurses in advanced countries for screening developmental delays in children. In a pilot study involving African children from age one month to six years in urban and suburban areas of Ibadan, Nigeria, results of screening with this tool identified many apparent delays in children from two to four years old in the area of language acquisition. It is probable that family background, in addition to sociocultural environment, may be responsible for most of the delays. A large-scale study to standardize this useful screening instrument to the norms of children in developing countries is suggested.

Child↗
PubMed1982

Obstructive sleep apnea in infants and children.

Twenty-two infants and children were found to have clinically significant obstructive sleep apnea. A history suggesting complete or partial airway obstruction during sleep was obtained on all patients, and physical examination of the sleeping patient revealed snoring, retractions, or OSA in 21 patients. Nevertheless, the mean delay in referral for 20 patients first seen after the neonatal period was 23 +15 (+ SD) months. Sixteen of 22 patients (73%) developed serious sequelae: cor pulmonale in 12 (55%), failure to thrive in six (27%), permanent neurologic damage in two (9%), and behavioral disturbances, hypersomnolence, or developmental delays in five (23%). Clinical and radiologic evaluations revealed anatomic abnormalities which narrowed the upper airway in 21 patients; enlarged tonsils and/or adenoids in 14, micrognathia in three,generalized facial abnormalities in three, and cleft palate repair/tonsillar hypertrophy in one. In five patients, upper airway fluoroscopy was performed and was helpful in establishing the site and mechanism of obstruction. Polygraphic monitoring was utilized to quantify the frequency and duration of OSA. Prolonged partial airway obstruction during sleep resulted in significant hypercarbia in 11 patients and hypoxemia in five. Twenty patients improved after surgery which relieved or bypassed the pharyngeal airway obstruction; two cases are pending. Increased awareness of OSA and examination of the sleeping patient should result in earlier treatment and less morbidity for infants and children with OSA.

Adenoids↗
PubMed1993

Otoacoustic emissions as a cross-check in pediatric hearing assessment: case report.

Audiologic assessment of infants and young children can be confounded by neurologic disorders or neuromaturational delays. In some cases, this results in an inability to assess hearing sensitivity by behavioral measures or by auditory evoked potentials. This case illustrates such an audiologic challenge. Subject DF was born with hydrocephaly, which was treated with repeated shunt surgeries and resulted in seizures and pervasive developmental delays. At 9 months of age, the child was tested by auditory brainstem response (ABR) measurement and found to have no response to sound. Believing that her child had hearing, DF's mother sought a second opinion. Results of an audiologic evaluation at 11 months of age showed no measurable behavioral responses in the sound field and an ABR abnormality that prevented prediction of hearing sensitivity. In contrast, sensitivity prediction by the acoustic reflex and results of both transient-evoked and distortion-product otoacoustic emissions predicted normal peripheral hearing sensitivity. This case illustrates the usefulness of otoacoustic emissions as an additional cross-check measure in pediatric hearing assessment.

Cochlea↗
PubMed1998

Atypical manifestations of two cases of trisomy 9 syndrome: rethinking development delay.

Trisomy 9 syndrome is characterized by "bulbous" nose, microphthalmia, dislocated limbs, and other anomalies of skeletal, cardiac, genitourinary, and central nervous systems. With the exception of one reported case study, all surviving infants have had severe mental impairment. The prospect of severe mental retardation often overwhelms parents who are faced with prenatal diagnosis of trisomy 9. We report on two new cases of mosaic trisomy 9, both of whom are only mildly developmentally delayed. One patient presented with the distinctive facial appearance, large fontanels, and joint abnormalities. The other had none of the typical congenital abnormalities. However, the patient was found to have a congenital heart defect and hypoplastic left heart syndrome, which to our knowledge has not been reported previously in the trisomy 9 syndrome. When these two patients are added to the published patients with this syndrome, there appears to be a range of manifestations, especially with respect to mental status, which has not fully been recognized.

Abnormalities, Multiple↗
PubMed1997

Effects of prenatal methylmercury exposure from a high fish diet on developmental milestones in the Seychelles Child Development Study.

Mercury is widespread in the environment and exists in several physical and chemical forms. Prenatal exposure to methylmercury disrupts brain development. The most common mode of prenatal methylmercury exposure is maternal fish consumption. Studies of human prenatal exposure in Iraq following maternal ingestion of methylmercury treated grain suggested that maternal hair mercury concentrations above 10 ppm may be related to delayed developmental milestones and neurological abnormalities. This level of exposure can be achieved by frequent consumption of fish. The Seychelles Child Development Study analyzed developmental milestones similar to those determined in Iraq in a large controlled, prospective study of children exposed prenatally to methylmercury when their mothers ate fish. As part of this ongoing study, cohort children were evaluated at 6.5, 19, 29, and 66 months of age. At 19 months care-givers were asked at what age the child walked (n=720 out of 738) and talked (n=680). Prenatal mercury exposure was determined by atomic absorption analysis of maternal hair segments corresponding to hair growth during the pregnancy. The median mercury level in maternal hair was 5.8 ppm with a range of 0.5-26.7 ppm. The mean age (in months) at walking was 10.7 (SD = 1.9) for females and 10.6 (SD = 2.0) for males. The mean age at talking (in months) was 10.5 (SD = 2.6) for females, and 11.0 (SD = 2.9) for males. After adjusting for covariates and statistical outliers, no association was found between the age at which Seychellois children walked or talked and prenatal exposure to mercury. Normal ages at achievement of the developmental milestones walking and talking were found in Seychellois toddlers following prenatal exposure to methylmercury from a maternal fish diet. These results do not support the lowest effect levels in young children following prenatal methylmercury exposure predicted by the dose response analysis of the Iraq data. More detailed studies in older children are needed to determine if there are adverse effects in fish eating populations.

Animals↗
PubMed2000

Mutant Rac1B expression in Dictyostelium: effects on morphology, growth, endocytosis, development, and the actin cytoskeleton.

Rac1 is a small G-protein in the Ras superfamily that has been implicated in the control of cell growth, adhesion, and the actin-based cytoskeleton. To investigate the role of Rac1 during motile processes, we have established Dictyostelium cell lines that conditionally overexpress epitope-tagged Dictyostelium discoideum wild-type Rac1B (DdRac1B) or a mutant DdRac1B protein. Expression of endogenous levels of myc- or GFP-tagged wild-type DdRac1B had minimal effect on cellular morphologies and behaviors. By contrast, expression of a constitutively active mutant (G12-->V or Q61-->L) or a dominant negative mutant (T17-->N) generated amoebae with characteristic cellular defects. The morphological appearance of actin-containing structures, intracellular levels of F-actin, and cellular responses to chemoattractant closely paralleled the amount of active DdRac1B, indicating a role in upregulating actin cytoskeletal activities. Expression of any of the three mutants inhibited cell growth and cytokinesis, and delayed multicellular development, suggesting that DdRac1B plays important regulatory role(s) during these processes. No significant effects were observed on binding or internalization of latex beads in suspension or on intracellular membrane trafficking. Cells expressing DdRac1B-G12V exhibited defects in fluid-phase endocytosis and the longest developmental delays; DdRac1B-Q61L produced the strongest cytokinesis defect; and DdRac1B-T17N generated intermediate phenotypes. These conditionally expressed DdRac1B proteins should facilitate the identification and characterization of the Rac1 signaling pathway in an organism that is amenable to both biochemical and molecular genetic manipulations.

Actins↗