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Results for “global developmental delay”

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At least 127 records · Page 7Linked to original sources

PubMed2000

Significant anticonvulsant side-effects in children and adolescents.

The anticonvulsant (AED) history for 216 children and adolescents with epilepsy was reviewed to determine the incidence and types of significant side effects (SSE) which warranted ceasing the drug (not due to a lack of response or a high dose). All parents of patients with epilepsy seen by the author over a 2 year period (March 1996 - March 1998) were questioned about SSE to previous AEDs, and the child's current therapy was also monitored prospectively to determine SSE. There were 107 girls and 109 boys ranging in age from 3 months - 18 years. Eighty-three patients had been exposed to a single AED while 133 had multiple AED exposures: mean 3.6 drugs; range 2-10 drugs. They were exposed to a total of 568 AEDs with SSE occurring in 15% of drug contacts: 7% due to behavioural changes such as irritability, aggression or hyperactivity; 8% were due to other factors such as a rash, headache, gastrointestinal disturbance or drowsiness. Fifty-seven children (26%) had experienced at least one SSE with 19 (9%) having SSE to more than one AED (range 2-4). Global developmental delay or an intellectual disability (ID) were present in 67 patients, and 27 (40%) of these experienced SSE compared with 30 (20%) of the group with normal cognition. This difference was principally due to the higher incidence of behavioural SSE in the ID group 28% versus 6% for the normal cognition group. Allowing for the higher number of AEDs used in the ID group (implying that their epilepsy was more difficult to control), behavioural SSE were still significantly more likely to occur in this group, i.e. 1: 9.6 drug exposures compared with 1: 31. 8 exposures for the normal cognition group (P<0.001). Monotherapy trials underestimate the true incidence of SSE in clinical practice as 26% of children had experienced at least one SSE and 9% had SSE to more than one AED. Those with ID were three times more likely to have behavioural SSE than children with normal cognition.

Adolescent↗

PubMed2003

Occipito-temporal polymicrogyria and subclinical muscular dystrophy.

We report a two-year-old Caucasian boy who had neonatal seizures and was found to have bilateral occipito-temporal polymicrogyria on neonatal brain MRI. The child had no additional neurological abnormality other than the neonatal seizures, but serum CK was found to be elevated (5 - 7 times normal values) and the muscle biopsy showed evidence of early muscular dystrophy. Detailed protein and genetic studies did not allow the identification of a known form of muscular dystrophy. The boy has been followed regularly and he currently has mild global developmental delay but no clinical signs of muscle involvement. The association of polymicrogyria and muscular dystrophy is known to occur in Fukuyama and Walker Warburg muscular dystrophies, in muscle-eye-brain disease and in some patients with merosin deficient CMD. However the absence of weakness and of eye involvement, the normal expression of merosin and alpha dystroglycan and the pattern of brain involvement make it very unlikely that the child is affected by one of these forms. As the pattern of brain involvement and the muscle pathology is not typical of one of the forms of neuronal migration disorders secondary to a known gene defect, we suspect that the combination of muscle and brain involvement found in this child is not coincidental. Our findings suggest that serum CK should be determined in children with undiagnosed polymicrogyria, even in the absence of weakness. This may lead to an expansion of our understanding of muscle dystrophies and cortical dysplasias.

Child, Preschool↗

PubMed2003

A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene.

Thyroid hormones are iodothyronines that control growth and development, as well as brain function and metabolism. Although thyroid hormone deficiency can be caused by defects of hormone synthesis and action, it has not been linked to a defect in cellular hormone transport. In fact, the physiological role of the several classes of membrane transporters remains unknown. We now report, for the first time, mutations in the monocarboxylate transporter 8 (MCT8) gene, located on the X chromosome, that encodes a 613-amino acid protein with 12 predicted transmembrane domains. The propositi of two unrelated families are males with abnormal relative concentrations of three circulating iodothyronines, as well as neurological abnormalities, including global developmental delay, central hypotonia, spastic quadriplegia, dystonic movements, rotary nystagmus, and impaired gaze and hearing. Heterozygous females had a milder thyroid phenotype and no neurological defects. These findings establish the physiological importance of MCT8 as a thyroid hormone transporter.

Base Sequence↗

PubMed1996

Frequency of linear hyperechogenicity over the basal ganglia in young infants with congenital rubella syndrome.

Five young infants with congenital rubella syndrome (CRS) underwent cranial ultrasonographic examinations and/or computed tomographic examinations. Only two of these infants were small for their gestational age, and none of them were microcephalic at birth. Deafness and ocular lesions were found in four patients, and congenital heart disease was found in three. All had abnormal ultrasonographic findings: linear-shaped hyperechogenicity over the basal ganglia was noted for five patients, periventricular punctate hyperechogenicity was noted for three, and subependymal cysts were observed in two. Follow-up ultrasonograms for two of the patients showed progressively enlarging hyperechogenic lesions. Calcification was found in both patients examined by means of computed tomography. All patients became microcephalic, with profound global developmental delay. Intracranial calcifications are common findings in patients with CRS. Ultrasonography should be performed for high-risk neonates, regardless of their symptoms. The finding of linear hyperechogenicity over the basal ganglia should prompt a search for all congenital infections, including CRS.

Basal Ganglia↗

PubMed2006

Patient with novel interstitial deletion of chromosome 3q13.1q13.3 and agenesis of the corpus callosum.

Interstitial deletions of the proximal long arm of chromosome 3 are rare. Only eight previously reported patients have deletions involving the proximal segment of 3q. Of these patients, three had agenesis of the corpus callosum and one had holoprosencephaly. We report here a patient with a small unique interstitial deletion of the long arm of chromosome 3 spanning 3q13.1q13.3. This patient has agenesis of the corpus callosum, global developmental delay, and distinctive facial features of a small nose, anteverted nares, and broad nasal root. Our patient provides further evidence that a gene involved in corpus callosum development or neuronal migration may reside in this region.

Agenesis of Corpus Callosum↗

PubMed2025

Biallelic variants in RNU2-2 cause the most prevalent known recessive neurodevelopmental disorder.

We recently showed that mutations in RNU4-2 and RNU2-2, two genes that are transcribed into small nuclear RNA (snRNA) components of the major spliceosome, are prevalent causes of dominant neurodevelopmental disorders (NDDs). By genetic association comparing 12,776 NDD cases with 56,064 controls, we now demonstrate the existence of a recessive form of RNU2-2 syndrome that, in England, is even more common than the dominant form. We inferred log Bayes factors for dominant and recessive models of association of 14.0 and 18.2, respectively, and observed 17 rare variants with a posterior probability of pathogenicity conditional on recessive association >0.8. This conservative threshold identified 18 probands (all with unaffected parents) and five affected siblings, each carrying two alleles in trans at these variants. A relaxed threshold of >0.6 identified a further 13 candidate probands. We estimate that recessive RNU2-2 syndrome accounts for 7-10% of families with a diagnosed recessive NDD, and is 36-62% as prevalent as the dominant RNU4-2-related disorder ReNU syndrome. We identified a further seven cases in five pedigrees in two replication collections. Cases are characterized by intellectual disability, global developmental delay and seizures. The variants are predicted to destabilize stem loops and binding domains of the U2-2 snRNA that contribute to spliceosome quaternary structure, intron recognition and catalytic function. Despite this, whole-blood derived RNA-seq data from three patients did not reveal splicing defects, in line with previous analogous observations for dominant RNU2-2 syndrome.

Journal Article↗

PubMed1996

Further evidence for a syndrome of "apple peel" intestinal atresia, ocular anomalies and microcephaly.

We report on a male child with "apple peel" atresia, associated with microcephaly, with subsequent hydrocephalus, short stature, moderate global developmental delay and ocular abnormalities. A similar phenotype was previously reported by Stromme et al. in 1993 in female siblings, and this description of another affected individual provides further evidence for this being a distinct syndromic entity.

Abnormalities, Multiple↗

PubMed1998

A case of insertional translocation involving chromosomes 2 and 4.

We report on a 6-year-old Caucasian boy with direct insertion of genetic material from the short arm of chromosome 4 to the short arm of chromosome 2. He was referred for evaluation because of global developmental delay and seizure disorder. A karyotype performed at 4 1/2 months of age, by a laboratory elsewhere, reportedly showed a deletion of chromosome 4(p12). When we saw him, he had macrocephaly, hypotonia, psychomotor retardation, multiple minor congenital anomalies, and EEG abnormalities. Repeat chromosomes performed by our laboratory revealed that his karyotype was 46,XY,dir ins(2;4)(p24;p15.3p13). Fluorescence in situ hybridization (FISH) analysis, using chromosomes 2 and 4 painting probes confirmed that material from 4p has been translocated to 2p. Also, FISH analysis using the Wolf-Hirschhorn critical region probe revealed that both loci are intact. Parental chromosomes were normal. This complex rearrangement, though it appears balanced, probably might have resulted in either a structural loss of genetic material or functional loss of a gene action. Thus, his phenotype could be explained by this de novo insertion of chromosome 4 material into chromosome 2. There is no reported case of this specific chromosome rearrangement.

Child↗

PubMed1996

Neurological outcome of severe cystic periventricular leukomalacia.

OBJECTIVE: To determine the neurological outcome of a cohort of premature babies having ultrasound diagnoses of severe cystic periventricular leukomalacia. METHODOLOGY: All neonatal intensive care unit admissions born at less than 35 weeks gestation or weighing less than 1500 g underwent serial cranial ultrasounds. Those developing severe bilateral cystic periventricular leukomalacia (12 patients) were then followed clinically to a mean age of 27.3 months. RESULTS: Ten of the 12 patients fulfilling strict ultrasound criteria survived. All had a major neurological handicap, all having spastic quadriparesis and visual impairments, with most suffering global developmental delay and epilepsy. CONCLUSIONS: Severe bilateral cystic periventricular leukomalacia results in major permanent handicap. It is currently impossible to identify most patients with this condition while they are being ventilated. Non-ultrasound techniques are needed to diagnose the condition earlier, and to give guidance to management.

Developmental Disabilities↗

PubMed2004

De novo interstitial duplication 4(q28.1q35) associated with choanal atresia.

We report a case of direct interstitial duplication of chromosome 4 from 4q28.1 to 4q35 associated with bilateral choanal atresia. The child also had dysmorphic features including a broad nasal bridge, telecanthus, downward slanting palpebral fissures, prominent ears, mild bilateral clinodactyly of the 5th fingers and bilateral hypoplasia of the 2nd-5th toenails. There was also a slightly dilated renal collecting system. At the age of 2.5 years, he had moderate global developmental delay, short, wide and tapering fingers, and short toes with hypoplastic toenails. To our knowledge, this is the second report of choanal atresia in a patient with trisomy 4q involving this region.

Adolescent↗

PubMed2004

Joubert syndrome: review and report of seven new cases.

Joubert syndrome (JS) is an autosomal-recessive disorder, characterized by hypotonia, ataxia, global developmental delay and molar tooth sign on magnetic resonance imaging. A variety of other abnormalities have been described in children with JS, including abnormal breathing, abnormal eye movements, a characteristic facial appearance, delayed language, hypersensitivity to noise, autism, ocular and oculomotor abnormalities, meningoencephaloceles, microcephaly, low-set ears, polydactyly, retinal dysplasia, kidney abnormalities (renal cysts), soft tissue tumor of the tongue, liver disease and duodenal atresia. Even within siblings the phenotype may vary, making it difficult to establish the exact clinical diagnostic boundaries of JS. We review the clinical characteristics of seven cases that fulfill the criteria of JS.

Abnormalities, Multiple↗

PubMed1984

Joubert's syndrome with retinal dysplasia: neonatal tachypnoea as the clue to a genetic brain-eye malformation.

Five children with features of Joubert's syndrome and Leber's amaurosis are described. The presenting symptoms were panting tachypnoea in the newborn, prolonged apnoeic attacks in the neonatal period (in both of identical twins), global developmental delay, and failure to develop vision. Three children had multiple hemifacial spasms, such as have been seen in Joubert's syndrome, and the same three had cystic dysplasia of the kidneys. Necropsy confirmed the retinal and renal pathology, together with agenesis of the vermis and brainstem dysgenesis in the identical twins. It is concluded that a gene for Leber's amaurosis may commonly manifest itself as the specific hind brain malformation underlying Joubert's syndrome. In infants with respiratory irregularities (especially rapid panting), hemifacial spasms, or developmental delay, absence of the cerebellar vermis should be specifically sought by ultrasound and computed tomography, and the electroretinogram measured, whether or not impaired vision is clinically evident.

Blindness↗

PubMed1989

The 'happy puppet' syndrome of Angelman: review of the clinical features.

Thirty six children with typical features of Angelman's syndrome, including global developmental delay, ataxia, episodes of paroxysmal laughter, seizures, and microcephaly were studied. The series included three sibships of three affected sisters, two affected brothers, and two affected sisters, respectively. The facial appearance is characterised by a prominent jaw, a wide mouth, and a pointed chin. Tongue thrusting is common. The movement disorder consists of a wide based, ataxic gait with frequent jerky limb movements and flapping of the hands. Tone is variable in the limbs with normal reflexes, and the plantar responses are usually flexor. The syndrome is being diagnosed more often, and attention is drawn to its diagnostic aspects.

Adolescent↗

PubMed2000

Long term outcome of twin-twin transfusion syndrome.

AIMS: To compare the perinatal mortality and morbidity of infants with twin-twin transfusion syndrome (TTTS) with those of gestation matched twin controls and to assess the neurodevelopmental outcome of surviving twins with TTTS. METHODS: A cohort of 17 consecutive pregnancies with TTTS was enrolled over three years together with gestation matched twin pregnancies unaffected by TTTS. Serial amnioreduction for the TTTS pregnancies was performed as appropriate. Perinatal death and neonatal morbidities were recorded for both the TTTS cohort and controls. The TTTS survivors had neurodevelopmental follow up to at least 2 years of age. RESULTS: In 12 of the pregnancies, serial amniocenteses were performed, but, in five, the infants were born before intervention. The mean gestational age at delivery was 29.1 weeks (range 23-36). There were five intrauterine deaths in the TTTS cohort and six neonatal deaths (survival 68%). In the control group, there was one intrauterine death and five neonatal deaths (survival 82%). Infants in the TTTS group had a greater requirement for inotropes (p = 0.04) and a higher incidence of renal failure (p = 0.005). Periventricular leucomalacia and cerebral atrophy were seen in 17% of the TTTS group, but none of the controls (p = 0.03). The 23 surviving TTTS infants were all followed up, with 22% having significant neurological morbidity: cerebral palsy and global developmental delay. CONCLUSIONS: Twins with TTTS have high perinatal mortality and neonatal morbidity, and long term neurodevelopmental morbidity in survivors is high. Further investigation into the pathogenesis and management of TTTS is required.

Acute Kidney Injury↗

PubMed1997

Dominantly inherited cerebral dysplasia: arachnoid cyst associated with mild mental handicap in a mother and her son.

We report a mother and son who each presented in infancy with hypotonia and global developmental delay. Subsequently, in both subjects, mild mental handicap was diagnosed in association with temporal lobe arachnoid cysts. Mendelian inheritance of this phenotype seems likely and macroscopic cerebral dysplasia in general may be underdiagnosed in people with familial, mild mental handicap.

Adult↗

PubMed2000

5p14 deletion associated with microcephaly and seizures.

We report on a father and son who have an interstitial deletion of 5p14. The father is clinically and mentally normal while the son has significant clinical involvement including microcephaly, seizures, and global developmental delay. The extent of the 5p14 deletion was determined using fluorescence in situ hybridisation (FISH). The deletion in this present family is smaller than a deletion previously described in a multigenerational family that lacks any clinical phenotype. This report shows that a 5p14 deletion does not always lead to a normal phenotype.

Child, Preschool↗

PubMed2006

Cognition and the sex chromosomes: studies in Turner syndrome.

Turner syndrome (TS) is a human genetic disorder involving females who lack all or part of one X chromosome. The complex phenotype includes ovarian failure, a characteristic neurocognitive profile and typical physical features. TS features are associated not only with complete monosomy X but also with partial deletions of either the short (Xp) or long (Xq) arm (partial monosomy X). Impaired visual-spatial/perceptual abilities are characteristic of TS children and adults of varying races and socioeconomic status, but global developmental delay is uncommon. The cognitive phenotype generally includes normal verbal function with relatively impaired visual-spatial ability, attention, working memory, and spatially dependent executive function. The constellation of neurocognitive deficits observed in TS is most likely multifactorial and related to a complex interaction between genetic abnormalities and hormonal deficiencies. Furthermore, other determinants, including an additional genetic mechanism, imprinting, may also contribute to cognitive deficits associated with monosomy X. As a relatively common genetic disorder with well-defined manifestations, TS presents an opportunity to investigate genetic and hormonal factors that influence female cognitive development. TS is an excellent model for such studies because of its prevalence, the well-characterized phenotype, and the wealth of molecular resources available for the X chromosome. In the current review, we summarize the hormonal and genetic factors that may contribute to the TS neurocognitive phenotype. The hormonal determinants of cognition in TS are related to estrogen and androgen deficiency. Our genetic hypothesis is that haploinsufficiency for gene/genes on the short arm of the X chromosome (Xp) is responsible for the hallmark features of the TS cognitive phenotype. Careful clinical and molecular characterization of adult subjects missing part of Xp links the TS phenotype of impaired visual spatial/perceptual ability to specific distal Xp chromosome regions. We demonstrate that small, nonmosaic deletion of the distal short arm of the X chromosome in adult women is associated with the same hallmark cognitive profile seen in adult women with TS. Future studies will elucidate the cognitive deficits and the underlying etiology. These results should allow us to begin to design cognitive interventions that might lessen those deficits in the TS population.

Adult↗

PubMed2003

Mental retardation and early onset of weakness in a girl with a dystrophinopathy and a large Xp21-23 deletion.

A 2-year-old girl presented with severe global developmental delay weakness, and an elevated serum creatine kinase level. Her muscle biopsy was consistent with an active dystrophy with absence of dystrophin in about half of the muscle fibers. Fluorescent in situ hybridization analysis showed her karyotype to be 46, X, delX p23.1-p21.1. This large deletion includes the dystrophin gene as well as the region involved in X-linked mental retardation. The genetic mechanism for the manifestation of both diseases is likely non-random inactivation of the X chromosome. To our knowledge, the combination of this dystrophinopathy in association with severe mental retardation has not been described in a girl.

Child, Preschool↗