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PubMed2004

Speech delay due to a prelinguistic regression of epileptic origin.

A 2-year-old boy presented with an early form of benign partial epilepsy with centro-temporal spikes (BCERS) and a severe speech delay. Family video analysis revealed an early regression of babbling and stagnation since the age of 12 months. Complete recovery occurred with anti-epileptic treatment. The deficit corresponded to a transient speech apraxia attributed to an epileptic disconnection of networks coordinating speech articulation. This observation is, to the best of our knowledge, the first demonstration that delayed emergence of language can be due to an epileptic dysfunction interfering with prelinguistic skills and therefore mimicking a developmental delay.

Child, Preschool↗
PubMed2003

The orphan steroid receptor Nur77 family member Nor-1 is essential for early mouse embryogenesis.

Nur77 and its family members, Nor-1 and Nurr1, are orphan steroid receptors implicated in a wide variety of biological processes, including apoptosis and dopamine neuron agenesis. Expression of these family members can be detected at low levels in many tissues but they are expressed at very high levels when cells are stimulated by outside signals, including serum, nerve growth factor, and receptor engagement. Introduction of a dominant negative Nur77 protein that blocks the activities of all family members led to inhibition of apoptosis in T cells. Nur77-deficient mice, however, exhibit no phenotype, and a line of Nor-1 mutant mice was reported to exhibit a mild ear development phenotype but no other gross abnormalities. Here, we report the generation of Nor-1-deficient mice with a block in early embryonic development. Nor-1 is expressed early during embryogenesis, and its loss leads to embryonic lethality around embryonic day 8.5 of gestation. The mutant embryos fail to complete gastrulation and display distinct morphological abnormalities, including a decrease in overall size, developmental delay and an accumulation of mesoderm in the primitive streak during gastrulation. Abnormal expression of a number of early developmental markers and defects in growth or distribution of emerging mesoderm cells were also detected. These data suggest that Nor-1 plays a crucial role in gastrulation.

Animals↗
PubMed1986

Effect of perinatal methimazole exposure on enolase isozymes in the developing rat.

The induction of hypothyroidism by methimazole produces a delay in CNS development as well as behavioral deficits in rat pups. Methimazole (0.1 mg/ml) was administered via drinking water to dams from gestational day 17 to postnatal day 10. Rat pup body weight was reduced on postnatal day 15 (P15) and 30 (P30) while brain weight was decreased only at P15. Soluble brain protein was decreased at P15 and P30. Total enolase and neuron-specific plus hybrid enolase (NSE+H) specific activity and activity were reduced on P15, while non-neuronal enolase (NNE) activity but not specific activity was depressed. At postnatal day 30, total enolase and NSE+H activity were slightly reduced, but NNE activity and the specific activities of total enolase, NNE and NSE+H were similar to controls. The ratio of NSE+H to NNE was reduced at P15 but not P30. The alterations in enolase activity following methimazole administration suggest a delay in the development and maturation of the CNS at P15. These results provide a biochemical correlate of the developmental delays reported in hypothyroid rat pups.

Age Factors↗
PubMed2003

Understanding mental retardation in Down's syndrome using trisomy 16 mouse models.

Mental retardation in Down's syndrome, human trisomy 21, is characterized by developmental delays, language and memory deficits and other cognitive abnormalities. Neurophysiological and functional information is needed to understand the mechanisms of mental retardation in Down's syndrome. The trisomy mouse models provide windows into the molecular and developmental effects associated with abnormal chromosome numbers. The distal segment of mouse chromosome 16 is homologous to nearly the entire long arm of human chromosome 21. Therefore, mice with full or segmental trisomy 16 (Ts65Dn) are considered reliable animal models of Down's syndrome. Ts65Dn mice demonstrate impaired learning in spatial tests and abnormalities in hippocampal synaptic plasticity. We hypothesize that the physiological impairments in the Ts65Dn mouse hippocampus can model the suboptimal brain function occuring at various levels of Down's syndrome brain hierarchy, starting at a single neuron, and then affecting simple and complex neuronal networks. Once these elements create the gross brain structure, their dysfunctional activity cannot be overcome by extensive plasticity and redundancy, and therefore, at the end of the maturation period the mind inside this brain remains deficient and delayed in its capabilities. The complicated interactions that govern this aberrant developmental process cannot be rescued through existing compensatory mechanisms. In summary, overexpression of genes from chromosome 21 shifts biological homeostasis in the Down's syndrome brain to a new less functional state.

Animals↗
PubMed1977

The nature of verbal interactions among handicapped and nonhandicapped preschool children.

The nature of verbal interactions among handicapped and nonhandicapped preschool children was examined in instructional and free-play settings. A wide variety of linguistic parameters designed to reflect verbal productivity and grammatical complexity was selected for analysis. The speech of designated nonhandicapped children wddressed. Listeners were classified as manifesting mild, moderate, severe, or no developmental delays. The results indicated that the speech of the designated children tended to be more complex, more frequent, and more diverse when addressed to developmentally more advanced children in both settings. These results were discussed in terms of their significance for facilitating the development of the language-delayed child.

Child, Preschool↗
PubMed2002

Setleis syndrome: three new cases and a review of the literature.

Setleis syndrome is characterized by cutis aplasia or atrophic skin at the temples, which is said to resemble forceps marks. There may also be a coarse facial appearance, anomalies of the eyelashes and eyebrows, and periorbital puffiness. The mouth has a typical appearance with large lips, inverted "V" contour, and downturned overly defined corners. Patients usually have normal intelligence. Here are presented three cases with features of Setleis syndrome. One is an apparently isolated case; the others are father and son. All three have developmental delay. This second family is a further example of autosomal dominant inheritance in Setleis syndrome. These patients also suggest that developmental problems may be a more common manifestation than previously described. Two of the patients are the first described of Pacific Island descent.

Abnormalities, Multiple↗
PubMed2004

Mild Wolf-Hirschhorn phenotype and partial GH deficiency in a patient with a 4p terminal deletion.

Wolf-Hirschhorn syndrome (WHS) is caused by a variably-sized deletion of chromosome 4 involving band 4p16 whose typical craniofacial features are "Greek warrior helmet appearance" of the nose, microcephaly, and prominent glabella. Almost all patients show mental retardation and pre- and post-natal growth delay. Patient was born at term, after a pregnancy characterized by intra-uterine growth retardation (IUGR). Delivery was uneventful. Developmental delay was evident since the first months of life. At 2 years, he developed generalized tonic-clonic seizures. Because of short stature, low growth velocity and delayed bone age, at 4 years he underwent growth hormone (GH) evaluation. Peak GH after two provocative tests revealed a partial GH deficiency. Clinical observation at 7 years disclosed a distinctive facial appearance, with microcephaly, prominent eyes, and beaked nose. Brain MRI showed left temporal mesial sclerosis. GTG banded karyotype was normal. Because of mental retardation, subtelomeric fluorescence in situ hybridization (FISH) analysis was performed, disclosing a relatively large deletion involving 4p16.2 --> pter (about 4.5 Mb), in the proband, not present in the parents. The smallest deletion detected in a WHS patient thus far includes two candidate genes, WHSC1 and WHSC2. Interestingly, that patient did not show shortness of stature, and that could be due to the haploinsufficiency of other genes localized in the flanking regions. Contribution of GH alterations and possible GH therapy should be further considered in WHS patients.

Abnormalities, Multiple↗
PubMed2000

Epilepsy surgery in infancy.

Surgery for intractable epilepsy is being offered at progressively younger ages, including infancy. The most common causes of catastrophic epilepsy in very young surgical candidates are focal malformations of cortical development and low-grade tumors. Additional causes include Sturge-Weber syndrome, epidermal nevus syndrome, hemimegalencephaly, and prenatal or perinatal infarction. Many infants manifest with focal seizures, whereas some patients have infantile spasms in the setting of a focal epileptogenic lesion. Video electroencepholography, magnetic resonance imaging, and positron emission tomography are critical investigations to explore surgical options. In small series, the percentage of infants free of seizures after surgery was in the range of 60%. This is similar to that seen after epilepsy surgery in older children, adolescents, and adults. However, larger series with long-term follow up will be important. Furthermore, the extensive procedures required in infants for removal of the epileptogenic developmental lesions entail some risk, and should not be offered in the absence of severe epilepsy. Most infant candidates for epilepsy surgery have significant developmental delay. Few data are available, but anecdotal experience suggests that surgical relief of catastrophic epilepsy may result in resumption of developmental progression. For each infant, the timing of surgery must be carefully considered based on full assessment of the relative risks and benefits, derived from a detailed presurgical evaluation.

Brain↗
PubMedDate not supplied

Apparent atypical callosal dysgenesis: analysis of MR findings in six cases and their relationship to holoprosencephaly.

The MR scans of six pediatric patients with apparent atypical callosal dysgenesis (presence of the dorsal corpus callosum in the absence of a rostral corpus callosum) were critically analyzed and correlated with developmental information in order to assess the anatomic, embryologic, and developmental implications of this unusual anomaly. Four patients had semilobar holoprosencephaly; the dorsal interhemispheric commissure in these four infants resembled a true callosal splenium. All patients in this group had severe developmental delay. The other two patients had complete callosal agenesis with an enlarged hippocampal commissure mimicking a callosal splenium; both were developmentally and neurologically normal. The embryologic implications of the presence of these atypical interhemispheric connections are discussed. Differentiation between semilobar holoprosencephaly and agenesis of the corpus callosum with enlarged hippocampal commissure--two types of apparent atypical callosal dysgenesis--can be made by obtaining coronal, short TR/TE MR images through the frontal lobes. Such differentiation has critical prognostic implications.

Abnormalities, Multiple↗
PubMed1989

A comparison of procedures in teaching self-help skills: increasing assistance, time delay, and observational learning.

The effectiveness and efficiency of two prompt-fading procedures were compared during the instruction of two self-help skills to four pairs of developmentally delayed preschoolers. In addition, the effect of observational learning was examined. Within a combined multiple probe and parallel treatments design, one member of each pair received direct instruction on the two skills. One skill was taught using an increasing assistance prompting procedure and the other skill was taught using a constant time delay procedure. The other member of the pair was prompted to observe the instruction, but was not taught directly. Reliability of scoring and procedural integrity were estimated, and social validity of outcomes considered. Findings indicated a slight but discernible advantage of using the time delay procedure rather than the increasing assistance procedure to teach complex, chained-response tasks. Further, considerable learning resulted solely from the observation of instruction.

Activities of Daily Living↗
PubMed2004

Neurodevelopmental outcomes of infant intestinal transplant recipients.

Little is known about the impact of intestinal transplantation on development of the infant brain. In this study we report four neurodevelopmental studies on children receiving either liver or intestinal/multivisceral transplants. Our preliminary investigation examined the pretransplant status of 27 infants, who were either liver or intestinal/multivisceral candidates, using the Bayley Scales of Infant Development. A second study examined 23 infants after liver or intestinal/multivisceral transplant. A third study included pre- and posttransplant evaluations on 5 multivisceral infant transplants. In the fourth study, 10 children were tested several years after intestinal/multivisceral transplantation. Some children are able to achieve a normal development. However, even several years posttransplant most children can still experience significant cognitive delays. Children receiving a transplant during infancy may also suffer severe motor delays. Infants undergoing intestinal/multivisceral transplantation show significantly more cognitive delays than those undergoing single-organ liver transplantation. In addition, multivisceral transplanted infants are more likely to continue to be severely developmentally delayed at the time of hospital discharge. With improved survival rates for infant transplants, both cognitive and motor development must be evaluated to determine the need for early intervention. In addition, educating families on the importance of compliance with intervention services outside the hospital is essential to maximize long-term neurodevelopmental outcomes for these infants.

Aging↗
PubMed1993

Intravenous pentazocine and methylphenidate abuse during pregnancy. Maternal lifestyle and infant outcome.

OBJECTIVE: To report the effects of intravenous abuse of pentazocine hydrochloride and methylphenidate hydrochloride during pregnancy. DESIGN: Retrospective chart review. PATIENTS: All pregnant women and their offspring, whose hospital records indicated prenatal abuse of pentazocine and methylphenidate during the 2-year study period. RESULTS: The median for maternal age was 22 years and the median number of prenatal visits was two. Twenty mothers had sexually transmitted diseases, 27 abused alcohol, 10 abused other drugs, and all smoked cigarettes. Eight infants were premature, and 12 were growth retarded. Four infants had congenital anomalies: fetal alcohol syndrome (two [twins]), structural heart defect (one), and polydactyly (one). Eleven infants were treated for neonatal abstinence syndrome. Seventeen infants had normal developmental quotients, and four had low-normal developmental quotients. CONCLUSIONS: Intrauterine exposure to pentazocine and methylphenidate appears to be associated with prematurity, growth retardation, and signs of neonatal withdrawal, but not with any particular teratogenic anomaly or severe developmental delay.

Adolescent↗
PubMed2000

Neuroblastoma associated with seizures and arrested development.

Two unrelated cases of childhood peripheral neuroblastoma associated with infantile seizures and developmental problems (but without opsoclonus-myoclonus) are presented. The considerable body of evidence supporting the view that the opsoclonus-myoclonus syndrome associated with neuroblastoma has an immunologic basis is reviewed. Patients with neuroblastoma and opsoclonus-myoclonus syndrome commonly have subsequent developmental problems and, rarely, may have seizures. The authors postulate that the seizures and developmental problems in their two patients may result from an immunologic mechanism similar to that suggested for the opsoclonus-myoclonus syndrome of neuroblastoma. The only laboratory evidence to support an immunologic mechanism in these two patients was the presence of raised cerebrospinal fluid immunoglobulins in Patient 2. Specific antineuronal antibody tests in Patient 2 were negative. It is therefore possible that the association reported in these two unrelated cases is coincidental. However, reasonably extensive investigations did not uncover an alternative etiology for the presence of the seizures and developmental delay.

Brain Neoplasms↗
PubMed1997

The embryonic development of sensory organs and the skull in the trisomy 16 mouse, an animal model for Down's syndrome.

The trisomy 16 mouse is a widely accepted animal model for the study of the embryonic development of human trisomy 21. While the development of the brain and heart has been thoroughly studied, there are hardly any data on the development of sensory organs like the eye, nose and ear. By studying scanning electron microscopic pictures and semithin sections from the tenth to the 15th day of development, we found delayed development of the nose, and, in particular, of the vomer. Sensory structures of the otic vesicle also showed a marked developmental delay. Pigmentation of the outer layer of the otic cup starts later in trisomic animals. Cleared specimens on day 16 showed retarded development of ossification centres in all areas of the skull. These findings correspond with the abnormal facial morphology found in Down's syndrome and may also provide new insights into the hearing impairment commonly found. The observations in the eye and skull bones indicate that neural crest tissue maldevelopment is not the sole cause of malformations.

Animals↗
PubMed1995

Progesterone, estradiol, and prolactin involvement in lactation, including lactation following a postpartum mating, in the Djungarian hamster (Phodopus campbelli).

The endocrinology of lactation in the Djungarian hamster was investigated through once-daily sampling of females on Days 0, 3, 6, 9, 12, 15, and 18 postpartum. Serum prolactin (PRL) was elevated during early lactation but declined with time. Serum progesterone (P4) levels were uniformly low, and serum estradiol (E2) levels increased after Day 9. New CL were formed after the postpartum ovulation and persisted throughout lactation. During the first 9 days, the CL had the high P4 content typical of pregnancy. After Day 9, each individual CL decreased in P4 content and increased in E2 content. As evidenced by the reappearance of large antral follicles, lactating females probably returned to ovulatory cycles at about that time. The Djungarian hamster has a postpartum estrus and is capable of delivering a second litter without a diapause (18 days), although the majority of second litters are delayed. Mating during the postpartum estrus had no detected effect on growth or survival of the first litter. Second pregnancies were developmentally delayed by 3 to 7 days. P4 was effectively absent from serum for the first 12 days after mating. Although CL contained high levels of P4, the CL remained small and poorly vascularized. Mated females did not have higher serum P4 levels than nonpregnant, lactating females until Day 18. In response to the competing demands of lactation and concurrent gestation, the endocrine conditions associated with pregnancy were the most affected.

Animals↗
PubMed2006

Emotional, developmental, and behavioral health of American children and their families: a report from the 2003 National Survey of Children's Health.

BACKGROUND: Recent children's health surveys have documented a high prevalence of emotional, developmental, and behavioral problems among children. Data from the 2003 National Survey of Children's Health provide new insights into these problems and their association with family function and community participation. These issues have become a current focus of the World Health Organization. METHODS: Answers to questions of interest from the 2003 National Survey of Children's Health were reported using estimates and SEs of rates. Statistical comparisons of rates with chi2 tests at the 0.05 level were made when relevant. RESULTS: The most commonly diagnosed problems among children 6-17 years of age were learning disabilities (11.5%), attention-deficit/hyperactivity disorder (8.8%), and behavioral problems (6.3%); among preschoolers, speech problems (5.8%) and developmental delay (3.2%) were most common. One in 200 children was diagnosed with autism. In contrast, rates of parental concerns about emotional, developmental, or behavioral problems were much higher; for example, 41% of parents had concerns about learning difficulties and 36% about depression or anxiety. Children with developmental problems had lower self-esteem, more depression and anxiety, more problems with learning, missed more school, and were less involved in sports and other community activities. Their families experienced more difficulty in the areas of childcare, employment, parent-child relationships, and caregiver burden. CONCLUSIONS: The most recent National Survey of Children's Health mirrored results of previous surveys regarding rates of diagnosed emotional, developmental, and behavioral problems, including an escalating diagnosis of autism among children. Reported rates of parental concerns about these problems were much higher, suggesting possible underdiagnosis of children's problems. Children with chronic problems had diminished family functioning, more school absences, and less participation in community activities compared with other children. Their parents experienced more difficulty with childcare, employment, and parenting skills. A change in treatment emphasis is needed, away from an exclusive focus on a child's developmental and behavioral problems to one that addresses the impacts of these problems on the family and community participation. A new approach to the way these issues are addressed and managed has the potential to enhance the quality of life for a child, as well as the parents, and to produce more meaningful and tangible solutions to these complex and increasingly evident problems.

Adolescent↗
PubMed1978

Selected developmental factors of cleft palate children between two and thirty-three months of age.

The literature suggests that cleft palate children and adults perform below their peers on both linguistic and nonlinguistic tasks. The purpose of this investigation was to ascertain if developmental delay could be observed in 24 cleft palate children below the age of three years when compared to matched controls. Three developmental scales were administered to all infants, and complete medical histories and current weights were obtained. Results indicated that the performance of the cleft palate subjects paralleled but fell below their peers on all developmental subtests. The differences were significant (p is less than .05) on three language subtests and on one personal-social and one motor subtest. The mean percentile weight also differed significantly (p is less than .05). Multivariate analysis explored the relationship of 1) extent of cleft, 2) sex, 3) hearing loss, 4) length of hospitalization, and 5) weight to the developmental scores. The extent of the cleft proved to be significant.

Child Development↗