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Anales de Pediatria (Barcelona, Spain :... Jul 2012Kabuki syndrome (OMIM: #147 920) presents as large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows,...
INTRODUCTION
Kabuki syndrome (OMIM: #147 920) presents as large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows, dysplastic ears and in most cases, with mental retardation. Patients have minor and major abnormalities in different systems. Its genetic basis is heterogeneous, but recently has been associated with mutations in gen MLL2.
CASE REPORTS
We present two patients with clinical features compatibles with the syndrome, mainly: large palpebral fissures with eversion of the lateral third of the lower eyelids, depressed nasal bridge, arched eyebrows, flat nose, persistent fingertip pads, cardiopathies and renal anomalies.
COMMENTARY
The diagnosis of this condition is clinical. The characteristics in the cases are compared with the patients reported in the literature. The importance of early diagnosis is to provide preventive management and an appropriate genetic counseling for the family.
Topics: Abnormalities, Multiple; Child; Face; Hematologic Diseases; Humans; Male; Phenotype; Vestibular Diseases
PubMed: 22387331
DOI: 10.1016/j.anpedi.2012.01.016 -
Clinical Oral Investigations Apr 2024To identify the characteristics of the oral microbiota and the relationship of the dental caries and periodontal status in patients aged 0 to 18 years with non-syndromic... (Meta-Analysis)
Meta-Analysis
Characterization of the oral microbiota and the relationship of the oral microbiota with the dental and periodontal status in children and adolescents with nonsyndromic cleft lip and palate. Systematic literature review and meta-analysis.
OBJECTIVE
To identify the characteristics of the oral microbiota and the relationship of the dental caries and periodontal status in patients aged 0 to 18 years with non-syndromic cleft lip and palate (CLP).
MATERIALS AND METHODS
A systematic review of the literature was carried out. Five databases were consulted, including publications in English, Spanish and Portuguese. The evaluations of the quality of the observational studies and the experimental studies were carried out with the Newcastle-Ottawa scale and CONSORT guidelines, respectively. The risk of bias of the studies was determined using Rev Manager 5.4, and 5 publications were meta-analyzed.
RESULTS
The cariogenic microbiota of children and adolescents with cleft lip and palate was similar to that of children without clefts, although with higher counts of Streptococcus mutans and Lactobacillus spp. The periodontopathogenic microbiota was related to the presence of Campylobacter spp, Fusobacterium spp, Fusobacterium nucleatum, Prevotella intermedia/nigrescens, Parvimonas micra and Porphyromonas gingivalis, considered microorganisms with high pathogenic capacity. Heterogeneity was shown in relation to the microbiota and the type of fissure, presenting numerous microorganisms associated with the pre- and post-surgical condition (cheilorrhaphy and palatorrhaphy) such as Staphylococcus aureus, Streptococcus beta hemolyticus, Klebsiella pneumoniae and Klebsiella oxytoca, Moraxella catarrhalis, Candida spp, Candida albicans, Candida krusei and Candida tropicalis. The meta-analysis revealed that patients with cleft lip and palate were 2.03 times more likely to have caries than the control group (p<0.005).
CONCLUSION
In the microbiota, there was a great diversity of microorganisms that can vary according to the type of fissure and surgical interventions predisposing patients to a greater probability of dental caries, it is important to take into account the technique used to describe the oral microbiota in order to be able to compare the different studies.
CLINICAL RELEVANCE
Studying the microbiota and the relationship of dental caries and periodontal status in children and adolescents with cleft lip and palate can facilitate the comprehensive care of patients with these conditions.
Topics: Child; Humans; Adolescent; Cleft Lip; Cleft Palate; Dental Caries; Microbiota
PubMed: 38587683
DOI: 10.1007/s00784-024-05624-3 -
Revista Paulista de Pediatria : Orgao... 2024To understand the experience of young people with orofacial clefts regarding life as an adolescent.
OBJECTIVE
To understand the experience of young people with orofacial clefts regarding life as an adolescent.
METHODS
Descriptive, qualitative study, developed in a Brazilian public and tertiary hospital, a reference center in the care of patients with craniofacial anomalies and related syndromes, between February and April 2019. The sample was defined by theoretical saturation. The following inclusion criteria were established: age between ten and 19 years old and having previously operated on orofacial cleft (lip and/or palate). Individuals with fissure associated with syndromes or other malformations were excluded. Data collection was performed through semi-structured interviews, which were audio recorded and transcribed in full. The trigger element was: how has it been for you to experience your adolescence? For the construction of the results, content analysis was used in the thematic modality.
RESULTS
Seventeen adolescents participated. From the speeches, three categories were revealed: interacting socially, feeling supported, and experiencing and facing prejudice.
CONCLUSIONS
The biopsychosocial and conflicting complexity that adolescents with orofacial clefts experience was noticed, as well as the importance of receiving support and establishing modalities of situational coping.
Topics: Humans; Cleft Palate; Cleft Lip; Adolescent; Female; Male; Qualitative Research; Child; Young Adult; Adaptation, Psychological; Brazil; Interviews as Topic
PubMed: 38716994
DOI: 10.1590/1984-0462/2024/42/2023131 -
Dermatology Online Journal Aug 2009A 21-year-old man presented with a life-long history of diffusely thickened skin with a grainy-to-ridged surface, verrucous perioral plaques with radial fissures, and...
A 21-year-old man presented with a life-long history of diffusely thickened skin with a grainy-to-ridged surface, verrucous perioral plaques with radial fissures, and diffuse palmoplantar keratoderma with a stippled appearance. These skin findings were accompanied by sensorineural hearing loss and keratoconjunctivitis, a clinical triad diagnostic of keratitis-ichthyosis-deafness (KID) syndrome. The patient also had a history of recurrent infections and cysts on the scalp. This report draws attention to inflammatory nodules (representing ruptured folliculitis), cysts, and recurrent infections on the scalp as manifestations of KID syndrome and reviews the increasingly recognized risk of follicular tumors and squamous-cell carcinomas in patients with this conditions.
Topics: Deafness; Humans; Ichthyosis; Keratitis; Male; Syndrome; Young Adult
PubMed: 19891919
DOI: No ID Found -
Clinical & Experimental Optometry May 2022
Topics: Choroid; Coloboma; Humans; Iris; Lens, Crystalline
PubMed: 34227911
DOI: 10.1080/08164622.2021.1945413 -
Communications Biology Sep 2023A molecular and functional link between neurotrophin signaling and cerebellar foliation is lacking. Here we show that constitutive knockout of two homologous genes...
A molecular and functional link between neurotrophin signaling and cerebellar foliation is lacking. Here we show that constitutive knockout of two homologous genes encoding the RNA binding protein RBM4 results in foliation defects at cerebellar lobules VI-VII and delayed motor learning in mice. Moreover, the features of Rbm4 double knockout (dKO), including impaired differentiation of cerebellar granule cells and dendritic arborization of Purkinje cells, are reminiscent of neurotrophin deficiency. Loss of RBM4 indeed reduced brain-derived neurotrophic factor (BDNF). RBM4 promoted the expression of BDNF and full-length TrkB, implicating RBM4 in efficient BDNF-TrkB signaling. Finally, prenatal supplementation with 7,8-dihydroxyflavone, a TrkB agonist, restored granule cell differentiation, Purkinje cell dendritic complexity and foliation-the intercrural fissure in particular-in the neonatal cerebellum of Rbm4dKO mice, which also showed improved motor learning in adulthood. This study provides evidence that prenatal activation of TrkB signaling ameliorates cerebellar malformation caused by BDNF deficiency.
Topics: Animals; Female; Mice; Pregnancy; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cerebellum; Cytoplasmic Granules; Nervous System Malformations
PubMed: 37670183
DOI: 10.1038/s42003-023-05294-z -
European Journal of Medical Genetics Feb 2022The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to...
The ARID1A gene is an infrequent cause of Coffin-Siris syndrome (CSS) and has been associated with severe to profound developmental delays and hypotonia in addition to characteristic craniofacial and digital findings. We present three fetuses and a male neonate with ventriculomegaly/hydrocephalus, absence of the corpus callosum (ACC), cerebellar hypoplasia, retinal dysplasia, lung lobulation defects, renal dysplasia, imperforate or anteriorly placed anus, thymus hypoplasia and a single umbilical artery. Facial anomalies included downslanting palpebral fissures, wide-spaced eyes, low-set and posteriorly rotated ears, a small jaw, widely spaced nipples and hypoplastic nails. All fetuses had heterozygous variants predicting premature protein truncation in ARID1A (c.4886dup:p.Val1630Cysfs*18; c.4860dup:p.Pro1621Thrfs*27; and c.175G>T:p.Glu59*) and the baby's microarray demonstrated mosaicism for a deletion at chromosome 1p36.11 (arr[GRCh37] 1p36.11(26,797,508_27,052,080)×1∼2), that contained the first exon of ARID1A. Although malformations, in particular ACC, have been described with CSS caused by pathogenic variants in ARID1A, prenatal presentations associated with this gene are rare. Retinal dysplasia, lung lobulation defects and absent thymus were novel findings in association with ARID1A variants. Studies in cancer have demonstrated that pathogenic ARID1A variants hamper nuclear import of the protein and/or affect interaction with the subunits of SWI/SNF complex, resulting in dysregulation of the PI3K/AKT pathway and perturbed PTEN and PIKC3A signaling. As haploinsufficiency for PTEN and PIKC3A can be associated with ventriculomegaly/hydrocephalus, aberrant expression of these genes is a putative mechanism for the brain malformations demonstrated in patients with ARID1A variants.
Topics: Abnormalities, Multiple; Aborted Fetus; Adult; DNA-Binding Proteins; Face; Female; Hand Deformities, Congenital; Humans; Intellectual Disability; Micrognathism; Mutation; Neck; Phenotype; Pregnancy; Prenatal Diagnosis; Transcription Factors
PubMed: 34942405
DOI: 10.1016/j.ejmg.2021.104407 -
Open Biology Mar 2018The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major...
The optic fissure is a transient gap in the developing vertebrate eye, which must be closed as development proceeds. A persisting optic fissure, coloboma, is a major cause for blindness in children. Although many genes have been linked to coloboma, the process of optic fissure fusion is still little appreciated, especially on a molecular level. We identified a coloboma in mice with a targeted inactivation of transforming growth factor β2 (TGFβ2). Notably, here the optic fissure margins must have touched, however failed to fuse. Transcriptomic analyses indicated an effect on remodelling of the extracellular matrix (ECM) as an underlying mechanism. TGFβ signalling is well known for its effect on ECM remodelling, but it is at the same time often inhibited by bone morphogenetic protein (BMP) signalling. Notably, we also identified two BMP antagonists among the downregulated genes. For further functional analyses we made use of zebrafish, in which we found TGFβ ligands expressed in the developing eye, and the ligand binding receptor in the optic fissure margins where we also found active TGFβ signalling and, notably, also gremlin 2b () and follistatin a (), homologues of the regulated BMP antagonists. We hypothesized that TGFβ is locally inducing expression of BMP antagonists within the margins to relieve the inhibition from its regulatory capacity regarding ECM remodelling. We tested our hypothesis and found that induced BMP expression is sufficient to inhibit optic fissure fusion, resulting in coloboma. Our findings can likely be applied also to other fusion processes, especially when TGFβ signalling or BMP antagonism is involved, as in fusion processes during orofacial development.
Topics: Animals; Bone Morphogenetic Proteins; Coloboma; Disease Models, Animal; Extracellular Matrix; Follistatin; Gene Expression Profiling; Intercellular Signaling Peptides and Proteins; Mice; Signal Transduction; Transforming Growth Factor beta2; Zebrafish; Zebrafish Proteins
PubMed: 29593116
DOI: 10.1098/rsob.170134 -
Italian Journal of Pediatrics May 2022Wolf-Hirschhorn syndrome (WHS) is a well-defined disorder, whose core phenotype encompasses growth restriction, facial gestalt, intellectual disability and seizures.... (Review)
Review
BACKGROUND
Wolf-Hirschhorn syndrome (WHS) is a well-defined disorder, whose core phenotype encompasses growth restriction, facial gestalt, intellectual disability and seizures. Nevertheless, great phenotypic variability exists due to the variable extent of the responsible 4p deletion. In addition, exome sequencing analyses, recently identified two genes, namely NSD2 and NELFA, whose loss-of-function variants contribute to a clinical spectrum consistent with atypical or partial WHS. The observation of patients exhibiting clinical features resembling WHS, with only mild developmental delay and without the typical dysmorphic features, carrying microdeletions sparing NSD2, has lead to the hypothesis that NSD2 is responsible for the intellectual disability and the facial gestalt of WHS. While presenting some of the typical findings of WHS (intellectual disability, facial gestalt, microcephaly, growth restriction and congenital heart defects), NSD2-deleted children tend to display a milder spectrum of skeletal abnormalities, usually consisting of clinodactyly, and do not exhibit seizures. We describe the clinical picture of a child with WHS due to a de novo mutation of NSD2 and discuss the clinical and diagnostic implications.
CASE PRESENTATION
A 6-year-old boy was evaluated for a history of intrauterine growth restriction, low birth weight, neonatal hypotonia, and psychomotor delay. No episodes of seizure were reported. At physical examination, he displayed marphanoid habitus, muscle hypotrophy and facial dysmorphisms consisting in high frontal hairline, upslanting palpebral fissures and full lips with bifid ugula. Cryptorchidism, shawl scrotum, mild clinodactyly of the right little finger and bilateral syndactyly of the II and III toes with sandal gap were also noted. The radiographic essay demonstrated delayed bone age and echocardiography showed mild mitral prolapse. Whole genome sequencing analysis revealed a heterozygous de novo variant of NSD2 (c.2523delG).
CONCLUSIONS
Full WHS phenotype likely arises from the cumulative effect of the combined haploinsufficiency of several causative genes mapping within the 4p16.3 region, as a contiguous genes syndrome, with slightly different phenotypes depending on the specific genes involved in the deletion. When evaluating children with pictures resembling WHS, in absence of seizures, clinicians should consider this differential diagnosis.
Topics: Chromosome Deletion; Chromosomes, Human, Pair 4; Haploinsufficiency; Humans; Intellectual Disability; Male; Phenotype; Seizures; Wolf-Hirschhorn Syndrome
PubMed: 35550183
DOI: 10.1186/s13052-022-01267-w -
Developmental Cell Jul 2007Here we identify the humpty dumpty (humdy) mouse mutant with failure to close the neural tube and optic fissure, causing exencephaly and retinal coloboma, common birth...
Here we identify the humpty dumpty (humdy) mouse mutant with failure to close the neural tube and optic fissure, causing exencephaly and retinal coloboma, common birth defects. The humdy mutation disrupts Phactr4, an uncharacterized protein phosphatase 1 (PP1) and actin regulator family member, and the missense mutation specifically disrupts binding to PP1. Phactr4 is initially expressed in the ventral cranial neural tube, a region of regulated proliferation, and after neural closure throughout the dorsoventral axis. humdy embryos display elevated proliferation and abnormally phosphorylated, inactive PP1, resulting in Rb hyperphosphorylation, derepression of E2F targets, and abnormal cell-cycle progression. Exencephaly, coloboma, and abnormal proliferation in humdy embryos are rescued by loss of E2f1, demonstrating the cell cycle is the key target controlled by Phactr4. Thus, Phactr4 is critical for the spatially and temporally regulated transition in proliferation through differential regulation of PP1 and the cell cycle during neurulation and eye development.
Topics: Actins; Animals; Cell Differentiation; Cell Division; Coloboma; Cytoskeletal Proteins; E2F1 Transcription Factor; Gene Expression Regulation, Developmental; Mice; Mice, Inbred C3H; Mice, Mutant Strains; Neural Tube Defects; Nuclear Proteins; Phenotype; Phosphoprotein Phosphatases; Phosphorylation; Protein Phosphatase 1; Retina; Retinoblastoma Protein
PubMed: 17609112
DOI: 10.1016/j.devcel.2007.04.018