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Results for “developmental disorders”

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At least 19 recordsLinked to original sources

PubMed2026

Expansion of the allelic and phenotypic spectrum of MED25-related developmental disorder: novel compound heterozygous variants with structural domain implications.

MED25-related developmental disorder (Basel-Vanagaite-Smirin-Yosef syndrome) is a rare autosomal recessive disorder, defined by severe neurodevelopmental delay, corpus callosum abnormalities, ocular involvement, epilepsy, and marked facial appearance. MED25 pathogenic variants interfere with the functioning of the Mediator complex, which is responsible for RNA polymerase II transcription. We report a 9-year-old girl who presents with significant global developmental delay, agenesis of the corpus callosum, congenital cataracts, epilepsy, hypotonia, musculoskeletal abnormalities, and typical craniofacial features. Trio-based whole-exome sequencing revealed compound heterozygous variants in MED25: a maternally transmitted truncating variant (c.1366 C > T; p.Gln456*) and a paternally inherited missense variant (c.430 C > T; p.Leu144Phe). The new classification of the missense variant as potentially pathogenic is supported by a systematic ACMG re-evaluation supported by segregation analysis, phenotypic specificity, computational prediction, and structural localization in the MED25 Activator Interaction Domain (ACID). Comparative phenotypic analyses show strong agreement with reported cases but add more data to fine-tune clinical spectrum. This article broadens the allelic and phenotypic spectrum of MED25-related developmental disorder and highlights the need for comprehensive evaluation across molecular, structural, and phenotypic pathways to elucidate variant signature in rare genetic disease models correctly.

Humans↗

PubMed2026

Mutation timing, accumulation, and selection in the male germline shape inheritance risk for developmental disorders.

De novo mutations (DNMs) in the paternal germline are a major cause of developmental disorders, but how mutation timing, paternal age, and spermatogonial selection jointly shape transmissible risk within individual fathers is unclear. We combined trio whole-genome sequencing from 167 families with deep targeted NanoSeq profiling of sperm from 127 fathers of children with confirmed pathogenic DNMs. Transmitted DNM burden and paternal sperm mutation burden, spectra, and selection landscape were indistinguishable from population reference cohorts. Six fathers carried pathogenic early mosaic variants detectable in sperm at variant allele fractions (VAFs) of 0.7%-14.8%, creating individual recurrence-risk outliers. However, early mosaics accounted for ∼8% of the cohort-aggregated pathogenic burden exome-wide, compared with ∼18% from known positively selected drivers and ∼74% from other rare variants accumulating with paternal age. Thus, paternal de novo disease risk is shaped primarily by universal age-associated mutation and selection, while early mosaicism creates uncommon but clinically important high-risk individuals.

DNMs↗

PubMed1976

Negotiating educational programs for children with developmental disorders: assessment, interpretation, demonstration, support (AIDS).

An approach to negotiating educational programs for children with multiple developmental problems is presented using two case examples from an interdisciplianry setting, the University Affiliated Cincinnati Center for Developmental Disorders. The use of the AIDS (Assessment, Intervention, Demonstration, Support) approach offers the schools evidence that the professional educator and psychologist are working in good faith and will not abandon them prematurely. Proper school placement through mediation also allows the school personnel to receive credit from the family for making the necessary changes, therefore not losing face with the parents. This approach seems particularly applicable to children with multiple and chronic problems who do not fit single special educational/diagnostic categories or labels.

Child Psychiatry↗

PubMed2025

Investigating the interplay between prematurity and genetic variation in the context of rare developmental disorders.

BACKGROUND: Rare damaging genetic variation accounts for a substantial proportion of the risk of rare developmental disorders (DDs), but common genetic variants as well as environmental factors, including prematurity, also contribute. Little is known about the interplay between prematurity and genetic variation in influencing phenotypic outcomes in DDs, nor about how genetic factors may contribute to risk of preterm birth in DDs. METHODS: We leveraged phenotypic and genetic data from 21,712 patients with DDs recruited for clinical sequencing, 16% of whom were born prematurely. Using multivariable regression models, we compared phenotypic features and the prevalence of diagnostic genetic variation in specific genes between preterm and term individuals with DDs. We tested whether the fraction of cases attributable to de novo mutations differed between term and preterm probands. Additionally, we assessed whether associations between common variant contributions to education-related traits and prematurity are explained by direct genetic effects. RESULTS: Prematurity was associated with more severe clinical phenotypes among these DD patients, including more affected organ systems and more delayed developmental milestones. Prematurity and the presence of a monogenic diagnosis contributed additively to severity. We found that genes associated with fetal anomalies were enriched for diagnostic mutations among preterm individuals (p = 7.83 × 10-5). We also demonstrated an exome-wide enrichment of de novo mutations (DNMs) in both term and preterm probands; the fraction of cases explained by DNMs in known DD-associated genes was higher in term than preterm cases (25% versus 20%) but DNMs in as-yet-undiscovered genes likely contribute approximately equally to both groups (14% versus 13%). Finally, we showed that the positive association between polygenic predisposition to education-related traits and gestational duration is likely to be the result of genetically influenced parental traits or confounders, rather than direct genetic effects in the child, and that a monogenic diagnosis modifies this association. CONCLUSIONS: Our findings emphasise the importance of considering environmental factors like prematurity in understanding outcomes in DDs suspected to have a genetic component, and motivate further exploration of the role that genetic variation plays in influencing prematurity.

Humans↗

PubMed1978

Vestibular hyporeactivity in infants at risk for schizophrenia. Association with critical developmental disorders.

Vestibular responses to caloric stimulation were measured from birth to age 2 years in ten infants born to schizophrenic mothers. This is part of a study of evolving neurointegrative disorders that may be associated with a genetic risk for schizophrenia. Transiently decreased vestibular responses coincided with several developmental disorders that were related to psychopathology at 10 years. Absent to decreased responses were associated with (1) a "pandevelopmental retardation" involving physical growth as well as postural-motor and visual-motor development, (2) an "abnormally quiet" state in the first month, and (3) failures of bimanual integration between 4 and 6 months. The transitory nature of the decreased nystagmus rules out the possibility of an organic lesion of the vestibular system. Rather, it suggests that some covert decrease in arousal accompanied those periods when central nervous system integration was disrupted.

Arousal↗

PubMed2026

Cohesin variants associated with human reproductive and developmental disorders.

The cohesin complex is an evolutionarily conserved multi-subunit protein assembly essential for sister chromatid cohesion, meiotic recombination, DNA double-strand break repair, and transcriptional regulation. Pathogenic variants in its subunits are implicated in a spectrum of reproductive and developmental disorders, including non-obstructive azoospermia, premature ovarian insufficiency, reproductive aging, aneuploidy, Cornelia de Lange syndrome, Roberts syndrome, cancer, and neuropsychiatric disease. Consequently, identifying cohesin mutations is a priority for precision diagnostics and personalized medicine. This review systematically summarizes the cohesin variants linked to these pathologies, exploring their molecular mechanisms and clinical manifestations. A deeper understanding of these variants is crucial not only for deciphering disease etiology but also for guiding the development of targeted diagnostic strategies and therapeutic interventions, ultimately improving patient management and outcomes.

Humans↗

PubMed1978

[Attitude of mothers towards physical punishment as a counseling problem in small children with developmental disorders].

Using the questionnaire that has been specifically developed to obtain data on parental educational behavior, 294 mothers of 2-year-old children were studied and their attitudes towards corporal punishment correlated with characteristics and symptoms of children as well as with psychosocial factors. Low level of education and lack of domestic happiness proved to be essential conditions for acceptance of corporal punishment. Children with developmental disorders are especially endangered only because of their particular liability to disorders, but on account of the fact that they do not receive the same amount of clemency as do children who are liable to infections. Problems of maleducation should receive greater attention in the elimination of environmental dangers to healthy development of children as well as in counseling.

Attitude↗

PubMed1976

[Several developmental disorders in children with schizophrenia].

The authors discusses some unclear and insufficiently studied problems related to early infantile autism, regress of development and underdevelopment of schizophrenic children. The basis of early infantile autism is most likely a peculiar disturbance of development due to constitutional, organic and psychogenic factors. In most of the cases this syndrome is connected with the schizophrenic process. The majority of psychiatrists in the Soviet Union consider lowering to a more early level of development as a regress of development in child schizophrenia symptoms. The clinical picture of retarded development in childhood schizophrenia depends upon the age of the onset of the disease and the degree of progressiveness of the process. Depending upon these criteria it is possible to distinguish retarded development, resembling oligophrenia and phenomena of psychophysical infantilism.

Autistic Disorder↗

PubMed1979