PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “global developmental delay”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 163 records · Page 9Linked to original sources
PubMed2026

[A case of bilateral open-lip schizencephaly with West syndrome due to variant of PAFAH1B1 gene and literature review].

OBJECTIVE: To report the clinical manifestations, genetic features, diagnosis, treatment, and prognosis of a child with bilateral open-lip schizencephaly complicated by West syndrome due to a variant of PAFAH1B1 gene, and review the relevant literature. METHODS: Clinical data of a 4-month-old boy were retrospectively analyzed, and 35 previously reported cases were systematically reviewed. This study was approved by the Medical Ethics Committee of Gansu Provincial People's Hospital (Ethics No.: 2025-871). RESULTS: The 4-month-old boy presented with clustered flexor spasms, hypsarrhythmia on electroencephalography, and developmental regression. Brain magnetic resonance imaging revealed bilateral pachygyria, schizencephaly, and dysgenesis of the corpus callosum. Trio whole-exome sequencing identified a de novo heterozygous NM_000430.4: c.703_704delAG (p.Glu235Metfs*20) frameshift variant in the PAFAH1B1 gene. Sanger sequencing confirmed that neither parent carried this variant. Based on the guidelines from American College of Medical Genetics and Genomics (ACMG), the variant has met the criteria for PVS1+PS2_Moderate+PM2_Supporting, and was classified as pathogenic. After treatment with adrenocorticotropic hormone combined with vigabatrin and other antiseizure medications, the epileptic spasms were controlled and the electroencephalographic abnormalities had improved. However, global developmental delay persisted at the 12-month follow-up. Analysis of the present case and 35 previously reported cases showed that PAFAH1B1-related phenotypes were highly consistent, mainly including infantile spasms (28/36), developmental delay/intellectual disability (29/36), and abnormal brain MRI findings (30/36), predominantly cortical malformations. The reported variant types included deletions, frameshift variants, nonsense variants, missense variants, and splice-site variants. CONCLUSION: PAFAH1B1 gene variants are an important cause for cortical malformations, including schizencephaly, and may lead to secondary West syndrome. This study has systematically summarized the genotypic and phenotypic features of bilateral open-lip schizencephaly complicated by West syndrome associated with a frameshift variant of the PAFAH1B1 gene. For infants with epileptic spasms or early-onset epilepsy accompanied by structural brain abnormalities, early genetic evaluation should be performed, and antiseizure treatment should be integrated with neurodevelopmental rehabilitation to facilitate long-term management.

Humans↗
PubMed2026

Whole-exome Sequencing Identifies Novel Candidate PCNT Variants in a Child With Overlapping MOPD II Features: A Case Report.

A 7-year-old Chinese boy presented with severe postnatal growth failure (height <3rd percentile at age 7 years), global developmental delay, moderate intellectual disability, and characteristic dysmorphic features including hypertelorism, short palpebral fissures, low-set ears, and a broad nasal bridge. A single electrocardiogram demonstrated a borderline corrected QT interval (QTc = 450 ms). No arrhythmias, QT-prolonging medications, electrolyte abnormalities, or relevant family cardiac history were identified. This finding warrants longitudinal cardiology follow-up and should not be interpreted as definitive Long QT syndrome. Whole-exome sequencing identified two novel missense variants in the PCNT gene (NM_006031.5): c.5675A>G (p.Glu1892Gly) in exon 28 and c.9734G>T (p.Arg3245Ile) in exon 45. Both variants were absent from gnomAD, ExAC, the 1000 Genomes Project database, and Chinese population databases, fulfilling ACMG criterion PM2. Although classified as variants of uncertain significance (VUS) because of limited functional evidence and conflicting in silico predictions, the variants occur in a gene associated with primordial dwarfism and are accompanied by partial phenotypic overlap with Microcephalic Osteodysplastic Primordial Dwarfism Type II (MOPD II). However, parental segregation analysis was unavailable; therefore, the variant phase could not be confirmed, and a recessive disease mechanism could not be established. These findings support the presence of candidate PCNT variants in an atypical primordial dwarfism phenotype and illustrate the utility of whole-exome sequencing for generating testable molecular hypotheses in genetically heterogeneous growth disorders. A definitive molecular diagnosis cannot be established at present, and the isolated borderline QTc finding requires further clinical evaluation.

Humans↗
PubMedDate not supplied

Deletion 3q in two patients with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES).

BACKGROUND: Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is an autosomal dominant condition mapped to chromosome 3q23. There are several reports of chromosomal abnormalities involving this region with a resultant phenotype that includes BPES. METHOD: We reassessed two unrelated boys ages 3 and 5 with BPES and associated nonocular abnormalities. Karyotype, which had been previously reported as normal, was repeated using high-resolution banding techniques, to look specifically at 3q23. Clinical findings were tabulated and compared with previously reported cases. RESULTS: Both patients proved to have interstitial deletions of chromosome 3, the first involving bands q22.2q25.1 and the second q22.2q24. The first patient exhibited prenatal and postnatal growth retardation, with global developmental delay, while the second patient had normal growth and development except for speech delay. Both had dysmorphic facies with BPES, flat philtrum, a thin upper lip, and small chin. In addition, the first boy had an inguinal hernia and hypospadius; the second boy had abnormal auricles and metatarsus adductus. The eight cases of interstitial deletions of 3q2 and six rearrangements involving this region have a remarkably similar phenotype. CONCLUSIONS: Deletion of 3q23 is a recognizable contiguous gene syndrome. Microdeletions of 3q23 should be ruled out in any sporadic case of BPES especially if there are associated nonocular abnormalities.

Blepharophimosis↗
PubMed1999

Anterior chamber eye anomalies, redundant skin and syndactyly--a new syndrome associated with breakpoints at 2q37.2 and 7q36.3.

We report a 34-year-old female with a de novo balanced reciprocal translocation involving 2q37.2 and 7q36.3. She has a unique combination of multiple congenital malformations that include redundant skin, complete tissue syndactyly of the hands and feet, hirsutism, polycystic ovaries and bilateral anterior chamber eye anomalies. Her son has inherited the unbalanced product (46,XY,der(2) t(2;7)(q37.2;q36.3). He has a similar clinical picture with additional features including complex congenital heart disease, post axial polydactyly, hypotonia and global developmental delay. The breakpoints may indicate the location of the gene(s) responsible for this unique combination of features.

Abnormalities, Multiple↗
PubMed2000

Ring chromosome 22 and autism: report and review.

Ring chromosome 22 has been described in over 50 cases. A characteristic phenotype has not been fully delineated; however, long face, thick eyebrows, 2-3 toe syndactyly, mental retardation, adequate somatic growth and the absence of major malformations are noted in many cases. An 11-year-old boy with ring chromosome 22 and 46,XY,r(22)(p11.31-q13.31 approximately q13.33) karyotype presented with global developmental delay, autistic disorder, and dolichocephaly, apparently low-set and large ears, midface hypoplasia, and 2-3 toe syndactyly. This is the second report of a ring chromosome 22 with autistic disorder. There appears to be an association between abnormalities of chromosome 22, including r(22), and autistic disorder; however, this occurrence may be a result of the association of autistic disorder with mental retardation rather than specifically due to r(22). The physical findings in this case also suggest that ring chromosome 22 causes a subtle but distinct phenotype which has previously been proposed.

Abnormalities, Multiple↗
PubMed2000

Deletion (9) (p13.1 p21.1).

We report on a 22-month-old girl with minor facial anomalies, global developmental delay, growth retardation, seizures, and leukoencephalopathy. Initial clinical assessment suggested the diagnosis of Williams syndrome. Results of fluorescence in situ hybridization testing for elastin were normal. However, chromosome analysis showed a 46,XX,del(9)(p13.1p21.1) karyotype in peripheral lymphocytes. Parental chromosomes were normal, indicating a de novo deletion. This patient's manifestations are compared with those of two other cases with overlapping deletions of the proximal short arm of chromosome 9.

Chromosome Banding↗
PubMed2000

A new association of congenital hydrocephalus, albinism, megalocornea, and retinal coloboma in a syndromic child: a clinical and genetic study.

We describe a child with global developmental delay, prominent metopic suture, trigonocephaly, and cryptorchidism whose symptoms resemble the well-known 9p deletion syndrome or 9p monosomy. We also noted congenital hydrocephalus, oculocutaneous albinism, retinal coloboma, and megalocornea, which are not typical features of 9p monosomy. When a new albinism gene was localized to 9p (Chintamaneni et al., Biochem Biophys Res Commun 1991;178:227-235; Murty et al., Genomics 1992;13:227-229), we hypothesized that our patient had the 9p deletion syndrome plus albinism, with the deletion involving the albinism gene. We used FISH probes to test this hypothesis and found that the 9p region was normal, therefore excluding the 9p deletion syndrome. To our knowledge, the association of congenital hydrocephalus, albinism, megalocornea, and retinal coloboma has not been described in the literature. The purpose of this report is to describe this new association of congenital ocular and cerebral anomalies in a syndromic child.

Abnormalities, Multiple↗
PubMed2003

A case of partial trisomy 13 presenting with hyperinsulinaemic hypoglycaemia.

We report on a newborn baby with partial trisomy 13 who presented with multiple dysmorphic features and hyperinsulinaemic hypoglycaemia. Cytogenetic study on peripheral blood lymphocytes showed 47,XY,+mar in all cells analysed; fluorescent in situ hybridisation showed that the marker was solely derived from chromosome 13. The final karyotype was 47,XY,+del(13)(q14q32). Milk formula through a nasogastric drip and intravenous glucose infusion were given to prevent further hypoglycaemia. However, the baby developed occasional episodes of hypoglycaemia during bolus feeding. Hence, diazoxide was given, at a dosage of 10 mg/kg per day from day 24. Thereafter, no hypoglycaemic episodes were detected. Subsequent follow-up revealed satisfactory growth, global developmental delay, and left divergent squint.

Abnormalities, Multiple↗
PubMedDate not supplied

Trisomy of 8q22.3 approximately q23-qter following an unbalanced 1;8 translocation in a boy with multiple anomalies.

An 11-month-old boy was first referred with global developmental delay, pallor and heart defects (ASD, VSD, mitral and tricuspid valve insufficiency). He also had facial abnormalities. Standard karyotyping showed additional material on one chromosome 1p homolog, and fluorescence in situ hybridization (FISH) indicated an unbalanced translocation of 1pter approximately p36.33 and 8q22.3 approximately q23. The breakpoint on p was found to reside very close to the telomere, making this a rare case of "almost pure" trisomy of 8q22.3 approximately q23-qter, without a significant partial 1p36 monosomy by FISH technique. The patient's face resembled the peculiar face in previously reported cases of 8q23-qter duplication. This report supports that critical gene(s) for cardiac septum formation reside on distal chromosome 8q.

Abnormalities, Multiple↗
PubMedDate not supplied

Neurophysiologic features in glutaric aciduria type I.

Neurophysiologic abnormalities are frequently seen in organic acidemias, but knowledge of the specific changes in the different types of organic acidemias is lacking. We studied electroencephalogram (EEG), visual evoked potential (VEP) and brain-stem auditory evoked response (BAER) in seven children with glutaric aciduria type I (GA1) to assess the neurophysiologic features in this rare inborn error of metabolism. Age at the time of the diagnosis ranged between 3 months and 36 months. Age at the time of neurophysiologic evaluation ranged between 11 months and 36 months. At the time of neurophysiologic evaluation, severe global developmental delay was seen in four patients, dystonia in four patients, motor delay in two patients, and axial hypotonia in two patients; macrocephaly, spasticity, moderate mental retardation and borderline intelligence were each seen in one patient. One patient had autistic features characterized by lack of language and social skills, poor eye contact and stereotypical behavior. Three of seven patients showed abnormal EEG findings. Two patients showed asymmetry with intermittent occipital delta slowing in one hemisphere. This finding probably indicates underlying cerebral dysfunction, and is not a specific feature. However, it suggests that these patients may develop abnormal EEG features during the course of the disease, and thus a baseline EEG may be useful for comparison over time. One patient showed high amplitude bursts of beta in the occipital regions with left predominance while on clonazepam and baclofen. We believe this finding was due to medication effect, and that what we observed was an exaggarated response to benzodiazepine. The clinical significance of this finding is unclear. VEP and BAER were available in four patients, and we found abnormalities in three of them. Neurophysiologic evaluation may be helpful in patients with GA1 as in other types of organic acidemias to help detect subtle changes that are not reflected by neurological examination or neuroimaging studies, and it may guide future treatment plans. Detailed neurophysiologic analysis in a large series of GA1 may yield further information regarding the extent of cerebral dysfunction.

Amino Acid Metabolism, Inborn Errors↗
PubMedDate not supplied

[Congenital insensitivity to pain with anhidrosis associated with congenital myasthenic syndrome].

INTRODUCTION: Congenital insensitivity to pain with anhidrosis (CIPA) or hereditary sensory and autonomic neuropathy type IV (HSAN IV) is a rare autosomal recessive disorder featuring recurrent fever episodes, inability to sweat, absent response to noxious stimuli, self mutilating behavior and mental retardation. It has been associated with mutations in the NTRK1 gene, located in 1q21-22 and encoding a high-affinity NGF receptor. CASE REPORT: An 8-year-old boy, the first son of consanguineous parents, presented with hypotonia, episodic hyperpyrexia and global developmental delay since the neonatal period. In addition to these signs, typical of CIPA, he displayed some other not previously described in this disease, such as facial dysmorphism, a severe swallowing disorder and a myogenic EMG pattern, that led to the initial suspicion of a muscle disorder. Molecular genetics studies uncovered a mutation c.C2011T in exon 15 of the NTRK1 gene. Genetic counselling was possible in the following pregnancy of the couple, where the female fetus was found to harbour the mutation in heterozygosity. The subsequent diagnosis of a congenital myasthenic syndrome in this sister led to neurophysiological re-evaluation of the probandus, in whom a myasthenic pattern of muscle activation was also found. CONCLUSIONS: A patient with CIPA and congenital myasthenic syndrome is described. CIPA must be the first diagnostic hypothesis when assessing a patient with insensitivity to pain, anhidrosis and self-mutilation. Given the rather homogeneous presentation of CIPA, the occurrence of atypical myopathic manifestations should raise the suspicion of a concurrent disorder. The present consanguineous kindred illustrates a rare instance of transmission of two mutated alleles giving rise to two unrelated, infrequent neurological syndromes.

Alleles↗
PubMed2006

Dopa-responsive dystonia (Segawa syndrome).

A 12 year old boy with gradually worsening global developmental delay was diagnosed and managed as quadriplegic cerebral palsy since child-hood. Subsequent evaluation revealed marked dystonia over spasticity leading to suspicion of Segawa syndrome. Dramatic improvement in clinical condition followed after therapy with low dose L-Dopa.

Cerebral Palsy↗
PubMed1995

[Epidemiology of developmental disorders in children in Tel Aviv].

We assessed the prevalence of developmental disorders, the need for intervention, potential for rehabilitation, and also characterized the risk factors, from files of 1,944 children referred during 1981-1990. The study group consisted of 4.3% of the children born in Tel Aviv during this period. Referral was highest between the ages 3-4 years and the causes for referral were language, speech and communication disorders (38%), global developmental delay (20%), motor disorders (16%), and behavioral and emotional problems (15%). Developmental disorders were more prevalent in boys (M/F ratio 1.8:1). 84% had at least 1 risk factor, either pre/perinatal, social or genetic. 66% had a social risk factor requiring involvement of a community social worker, or a parent with a chronic disease. The principal genetic risk factors were a developmental problem in a sibling, and parental consanguinity. The most common perinatal risk factors were birth weight under 2500 grams, hyperbilirubinemia of the newborn and severe asphyxia. Prognosis was good: 83% had normal intelligence and only 10% had severe disability. Upon discharge from the development center at the age of 5 years only 18% required special schooling, but 63% were referred for continuation of rehabilitation services. This study provides multi-disciplinary information that allows planning of requirements for diagnostic, therapeutic and rehabilitation services in the human, logistic and economic fields.

Child↗
PubMedDate not supplied

A constellation of dental anomalies in a chromosomal deletion syndrome (7q32): case report.

A case is reported of a patient with deletion of the long arm of chromosome 7 at a highly specific locus (7q32). In addition to significant craniofacial stigmata and global developmental delay, the patient presented with numerous clinical and radiographic dental anomalies observed over a 10-year period. Hypodontia, accessory roots, dens invaginatus, hypoplastic enamel, and numerous pulpal anomalies all were noted. Some of these dental findings suggest trichodentoosseous syndrome (TDO), although the other stigmata do not. The wide variety of dental findings in this patient may help to define the role of chromosome 7q32 in dental development.

Abnormalities, Multiple↗
PubMed1993

Infants of less than 1250 grams birth weight at Groote Schuur Hospital: outcome at 1 and 2 years of age.

A prospective 2-year follow-up study of infants with birth weights of less than 1250 g was undertaken at Groote Schuur Hospital Neonatal Intensive Care Unit. For a 12-month period beginning July 1988, all live infants born at Groote Schuur Hospital or referred to the Neonatal Intensive Care Unit were included in the study cohort. The aim of the study was to document the morbidity, mortality, and neurodevelopmental outcome of these infants to 2 years of age. Of 235 liveborn infants, 143 (61%) survived to discharge. One hundred twenty-six infants were born weighing less than 1000 g; 42% survived to discharge. One hundred nine infants weighed 1000 g or more at birth, and 83% survived to discharge. Better survival was documented for infants whose mothers attended antenatal care, who weighed more than 900 g, and who were of greater than 30 weeks' gestation. Eleven infants died in the first 6 months after discharge. One hundred six infants (83% of survivors) underwent Griffiths developmental testing and clinical assessment at 1 year of age. Ninety-six (91%) of these survivors were seen and tested at 2 years of age. Of the 106 infants assessed at 1 year of age, 6 infants had cerebral palsy, 6 were globally developmentally delayed without signs of cerebral palsy, and 1 infant showed significant motor delay with a normal developmental quotient. At 2 years of age 1 additional infant had cerebral palsy and 9 more infants are likely to be mentally retarded. At 2 years of age the major handicap rate was, therefore, 22%. Sixty-nine percent of surviving infants, and all but 1 of the infants with cerebral palsy, were underweight for gestational age at birth. There was a tendency for these underweight-for-gestational-age infants to score less well at 2 years of age. Infants who received ventilation and infants with a birth weight of less than 1000 g were not found to score less well than other infants in the cohort.

Birth Weight↗
PubMed1996

[Findings in cerebral proton spin resonance spectroscopy in newborn infants with asphyxia, and psychomotor development].

OBJECTIVE: To determine the relationship between the results of cerebral proton magnetic resonance spectroscopy (1H-MRS) and neuromotor development in neonates with hypoxia. DESIGN: Descriptive. SETTING: Wilhelmina Childrens' Hospital and University Hospital, Utrecht, The Netherlands. METHODS: 32 infants with hypoxic-ischaemic encephalopathy (Sarnat grade I (mild; n = 5), grade II (moderate; 20), grade III (severe; 7)) were examined at a mean of 8 days following the hypoxic event (range 2-22). 1H-MRS of the periventricular white matter and part of the basal ganglia was performed in a 1.5 T field: TR/TE: 2000/272 ms. Peak-to-peak NAA/Cho ratios were calculated. The presence of a lactate resonance was considered abnormal. Assessment of neuromotor development of the survivors was performed at 6, 9 and 18 months of age. RESULTS: 6 patients died (all grade III), 10 survived with handicaps (I grade III, 9 grade II). Handicaps consisted of spastic quadriplegia (n = 7), hemiplegia and mental retardation (n = 1), and global developmental delay (n = 2). The other 16 survivors were normal at 18 months. 1H-MRS showed NAA/Cho ratios of 0.97 (SD:0.13) in the patients with a normal outcome and 0.74 (0.17) in the patients with an adverse outcome (handicaps or death); p < 0.0001 (t-test). Lactate was demonstrated in all 7 grade III neonates, but not in any of the other infants. CONCLUSION: Cerebral 1H-MRS was related to neurodevelopmental outcome of neonates with HIE. A low NAA/Cho ratio and presence of a lactate resonance predicted an adverse outcome.

Asphyxia Neonatorum↗
PubMed1996

[Pyruvate dehydrogenase deficiency and cerebral malformations].

Pyruvate dehydrogenase (PDH) deficiency is a major cause of primary lactic acidosis and severe global developmental delay. A deficiency of PDH E1 alpha, a subunit of the PDH complex is a prominent cause of congenital lactic acidosis. The E1 alpha cDNA and corresponding genomic DNA have been located in the short arm of the X-chromosome (Xp22-1). A isolated 'cerebral' lactic acidosis with cerebral dysgenesis is a recognized pattern of presentation of PDH deficiency. Here, we report clinical features, magnetic resonance, and biochemical studies of two females aged 6 months (case 1) and 26 months (case 2). Both had severe development delay, minor dysmorphic features, microcephaly, severe hypoplasia of the corpus callosum, cerebral atrophy, ventricular dilatation and increase in serum lactate levels without systemic acidosis. Urinary organic acid profile was compatible with PDH deficiency. Increased CSF lactate and pyruvate levels and reduced total PDH and PDH E1 activities in muscle and fibroblasts were observed in case 1. Otherwise, decreased total PDH activity in muscle but not in fibroblasts was seen in case 2. The PDH E1á gene was sequenced in the case 1 and a deletion in exon 7 was demonstrated. Dysmorphism with severe cerebral malformations in female patients merits a metabolic evaluation, including determination of lactate and pyruvate levels in CSF.

Brain↗