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JPMA. the Journal of the Pakistan... Apr 2023Coffin-Siris syndrome (CSS) is a rare congenital genetic syndrome, a multisystem disease related to congenital abnormalities, that manifests with abnormal features,...
Coffin-Siris syndrome (CSS) is a rare congenital genetic syndrome, a multisystem disease related to congenital abnormalities, that manifests with abnormal features, causes repeated infections and is associated with developmental delays. Here, we report a newborn male with CSS from Baoding in the Hebei Province of China.
Topics: Infant, Newborn; Humans; Male; Intellectual Disability; Abnormalities, Multiple; Micrognathism; Hand Deformities, Congenital; Neck
PubMed: 37052010
DOI: 10.47391/JPMA.5157 -
Frontiers in Pediatrics 2023This study will list the most common comorbidities of congenital facial nerve palsy and how to detect and treat them, with special attention for ENT-problems such as...
OBJECTIVES
This study will list the most common comorbidities of congenital facial nerve palsy and how to detect and treat them, with special attention for ENT-problems such as hearing loss. Congenital facial nerve palsy is a very rare entity but in UZ Brussels hospital there was a follow-up of 16 children in the last 30 years.
METHODS
Literature review has been done, combined with thorough research of our own series of 16 children with congenital facial nerve palsy.
RESULTS
Congenital facial nerve palsy can be part of a known syndrome, most commonly Moebius syndrome, but can also appear solely. It appears often bilateral and with a severe gradation. In our series, hearing loss is frequently seen in association with congenital facial nerve palsy. Other abnormalities are dysfunction of the abducens nerve, ophthalmological problems, retro- or micrognathism and abnormalities of limbs or heart. The majority of the children in our series underwent radiological imaging (CT and/or MRI): the facial nerve but also the vestibulocochlear nerve and middle and inner ear can be evaluated.
CONCLUSION
A multidisciplinary approach of congenital facial nerve palsy is recommended as it can affect various bodily functions. Radiological imaging needs to be done to acquire additional information that can be useful for diagnostic and therapeutic purposes. Although congenital facial nerve palsy may not be treatable itself, its comorbidities can be treated and improve the quality of life of the affected child.
PubMed: 36891227
DOI: 10.3389/fped.2023.1077238 -
International Journal of Molecular... Feb 2023SOX4 is a transcription factor with pleiotropic functions required for different developmental processes, such as corticogenesis. As with all SOX proteins, it contains a...
SOX4 is a transcription factor with pleiotropic functions required for different developmental processes, such as corticogenesis. As with all SOX proteins, it contains a conserved high mobility group (HMG) and exerts its function via interaction with other transcription factors, such as POU3F2. Recently, pathogenic variants have been identified in several patients who had clinical features overlapping with Coffin-Siris syndrome. In this study, we identified three novel variants in unrelated patients with intellectual disability, two of which were de novo (c.79G>T, p.Glu27*; c.182G>A p.Arg61Gln) and one inherited (c.355C>T, p.His119Tyr). All three variants affected the HMG box and were suspected to influence SOX4 function. We investigated the effects of these variants on transcriptional activation by co-expressing either wildtype (wt) or mutant with its co-activator POU3F2 and measuring their activity in reporter assays. All variants abolished SOX4 activity. While our experiments provide further support for the pathogenicity of loss-of-function (LOF) variants as a cause of syndromic intellectual disability (ID), our results also indicate incomplete penetrance associated with one variant. These findings will improve classification of novel, putatively pathogenic variants.
Topics: Humans; Abnormalities, Multiple; Gene Expression Regulation; Intellectual Disability; Micrognathism; SOXC Transcription Factors; Transcription Factors
PubMed: 36834931
DOI: 10.3390/ijms24043519 -
Plastic and Reconstructive Surgery May 2023Craniofacial microsomia (CFM) is characterized by several malformations related to the first and second pharyngeal arch. Patients typically present with facial...
BACKGROUND
Craniofacial microsomia (CFM) is characterized by several malformations related to the first and second pharyngeal arch. Patients typically present with facial asymmetry, but extracraniofacial organ systems might be involved, including limb anomalies. The purpose of this study was to analyze the occurrence of upper and lower limb anomalies in CFM patients. Furthermore, the relation between limb anomalies and the OMENS+ (orbital distortion; mandibular hypoplasia; ear anomaly; nerve involvement; soft-tissue deficiency; and associated extracraniofacial anomalies) classification was examined.
METHODS
A retrospective study was conducted including patients with CFM from craniofacial units in three different countries. Patients were included when clinical and/or radiographic images were available. Demographic, radiographic, and clinical information was obtained.
RESULTS
A cohort of 688 patients was available and selected for analysis. In total, 18.2% of the patients were diagnosed with at least one upper and/or lower limb anomaly. Upper and lower limb anomalies were seen in, respectively, 13.4% and 7.8% of patients. Patients with other extracraniofacial anomalies had a significantly higher risk for limb anomalies (OR, 27.98; P = 0.005). Laterality of CFM and a higher OMENS score were not associated with limb anomalies.
CONCLUSIONS
More than one in six patients with craniofacial microsomia have limb anomalies. Therefore, clinical awareness for these anomalies is warranted. Examination and, if present, follow-up on limb abnormalities in patients with CFM should be implemented in the standard assessment of CFM patients.
CLINICAL QUESTION/LEVEL OF EVIDENCE
Risk, III.
Topics: Humans; Goldenhar Syndrome; Retrospective Studies; Facial Asymmetry; Micrognathism; Lower Extremity
PubMed: 36729069
DOI: 10.1097/PRS.0000000000010090 -
G3 (Bethesda, Md.) Aug 2023Loss-of-function mutations of FIG4 are responsible for neurological disorders in human and mouse that result from reduced abundance of the signaling lipid PI(3,5)P2. In...
Loss-of-function mutations of FIG4 are responsible for neurological disorders in human and mouse that result from reduced abundance of the signaling lipid PI(3,5)P2. In contrast, loss-of-function mutations of the phosphoinositide kinase PIP4K2C result in elevated abundance of PI(3,5)P2. These opposing effects on PI(3,5)P2 suggested that we might be able to compensate for deficiency of FIG4 by reducing expression of PIP4K2C. To test this hypothesis in a whole animal model, we generated triallelic mice with genotype Fig 4-/-, Pip4k2c+/-; these mice are null for Fig 4 and haploinsufficient for Pip4k2c. The neonatal lethality of Fig 4 null mice in the C57BL/6J strain background was rescued by reduced expression of Pip4k2c. The lysosome enlargement characteristic of Fig 4 null cells was also reduced by heterozygous loss of Pip4k2c. The data demonstrate interaction between these two genes, and suggest that inhibition of the kinase PIPK4C2 could be a target for treatment of FIG4 deficiency disorders such as Charcot-Marie-Tooth Type 4J and Yunis-Varón Syndrome.
Topics: Mice; Animals; Humans; Mice, Inbred C57BL; Phosphoric Monoester Hydrolases; Cleidocranial Dysplasia; Micrognathism; Phenotype; Phosphatidylinositols; Flavoproteins; Phosphoinositide Phosphatases; Phosphotransferases (Alcohol Group Acceptor)
PubMed: 36691351
DOI: 10.1093/g3journal/jkad007 -
Pediatrics and Neonatology Mar 2023
Topics: Humans; Sotos Syndrome; Abnormalities, Multiple; Intellectual Disability; Face; Micrognathism; Neck
PubMed: 36564311
DOI: 10.1016/j.pedneo.2022.10.005 -
Nature Communications Dec 2022The cohesin complex participates in many structural and functional aspects of genome organization. Cohesin recruitment onto chromosomes requires nucleosome-free DNA and...
The cohesin complex participates in many structural and functional aspects of genome organization. Cohesin recruitment onto chromosomes requires nucleosome-free DNA and the Scc2-Scc4 cohesin loader complex that catalyzes topological cohesin loading. Additionally, the cohesin loader facilitates promoter nucleosome clearance in a yet unknown way, and it recognizes chromatin receptors such as the RSC chromatin remodeler. Here, we explore the cohesin loader-RSC interaction. Amongst multi-pronged contacts by Scc2 and Scc4, we find that Scc4 contacts a conserved patch on the RSC ATPase motor module. The cohesin loader directly stimulates in vitro nucleosome sliding by RSC, providing an explanation how it facilitates promoter nucleosome clearance. Furthermore, we observe cohesin loader interactions with a wide range of chromatin remodelers. Our results provide mechanistic insight into how the cohesin loader recognizes, as well as influences, the chromatin landscape, with implications for our understanding of human developmental disorders including Cornelia de Lange and Coffin-Siris syndromes.
Topics: Humans; Chromatin; Saccharomyces cerevisiae Proteins; Cell Cycle Proteins; Nucleosomes; Chromosome Segregation; Micrognathism
PubMed: 36509793
DOI: 10.1038/s41467-022-35444-6 -
Head & Face Medicine Nov 2022Genetic and environmental factors especially climatic conditions are thought to influence the shape and size of the paranasal sinuses and anatomic variations may create...
BACKGROUND
Genetic and environmental factors especially climatic conditions are thought to influence the shape and size of the paranasal sinuses and anatomic variations may create both a diagnostic and therapeutic challenge. However, no study has been published about the climatic adaptation of the paranasal sinus region in different populations. This study aimed to compare the prevalence of anatomical variants in the paranasal sinus and nasal cavity using Cone-Beam Computed Tomography (CBCT) between Polish and Turkish Cypriot populations.
METHODS
The material consisted of volumes acquired utilizing Galileos (Sirona, Germany) as well as Newtom 3G (QR Verona, Newtom, Italy) CBCT units. There were examined 356 Polish and 359 Turkish Cypriot patients in whom paranasal sinuses were included in the field of view. Paranasal sinus anatomic variations were assessed in both populations.
RESULTS
In the Polish population, the most common anatomic variation was septum deviation followed by the Agger nasi cell and concha bullosa with a prevalence of 87.7%, 83.2%, and 54.8% respectively. For the Turkish Cypriot population, the most common anatomic variation was Agger nasi cell followed by concha bullosa and supraorbital ethmoid cells with a prevalence of 81.6%, 68%, and 57.8% respectively. Many anatomic variations were found to show substantial differences among both populations. Incidence rates of hyperpneumatization of the frontal sinus, septum pneumatization, supraorbital ethmoid cells, concha bullosa, uncinate bulla, and internal carotid artery protrusion into the sphenoid sinus were significantly higher in the Turkish Cypriot group, while the incidence of Haller cell, frontal sinus hypoplasia, maxillary sinus hypoplasia, ethmomaxillary sinus, sphenomaxillary plate, and septum deviation were significantly higher in Polish population.
CONCLUSION
According to the Köppen-Geiger world climatic map, the climate is warmer and drier in Turkish Cypriote populations than in the Polish population. These climatic differences influence the paranasal sinus variations between the Turkish Cypriot and Polish populations that must be taken into account by rhinologic surgeons especially when performing frontal and sphenoid sinus surgery.
Topics: Humans; Nasal Cavity; Poland; Spiral Cone-Beam Computed Tomography; Tomography, X-Ray Computed; Maxillary Sinus; Micrognathism
PubMed: 36435801
DOI: 10.1186/s13005-022-00340-3 -
American Journal of Medical Genetics.... Jan 2023Coffin-Siris syndrome (CSS, OMIM#135900) is a rare congenital disorder associated with neurodevelopmental and dysmorphic features. The primary cause of CSS is pathogenic...
Coffin-Siris syndrome (CSS, OMIM#135900) is a rare congenital disorder associated with neurodevelopmental and dysmorphic features. The primary cause of CSS is pathogenic variants in any of 9 BAF chromatin-remodeling complex encoding genes or the genes SOX11 and PHF6. Herein, we performed whole-exome sequencing (WES) and a series of analyses of growth-related, auditory, and radiological findings in two probands with syndromic sensorineural hearing loss and inner ear malformations who exhibited distinctive facial features, intellectual disability, growth retardation, and fifth finger malformation. Two de novo variants in the SOX11 gene (c.148A>C:p.Lys50Asn; c.811_814del:p.Asn271Serfs*10) were detected in these probands and were identified as pathogenic variants as per ACMG guidelines. These probands were diagnosed as having CSS based upon clinical and genetic findings. This is the first report of CSS caused by variants in SOX11 gene in Chinese individuals. Deleterious SOX11 variants can result in sensorineural hearing loss with inner ear malformation, potentially extending the array of phenotypes associated with these pathogenic variants. We suggest that both genetic and clinical findings be considered when diagnosing syndromic hearing loss.
Topics: Humans; Micrognathism; Hand Deformities, Congenital; Intellectual Disability; Neck; Hearing Loss, Sensorineural; SOXC Transcription Factors
PubMed: 36369738
DOI: 10.1002/ajmg.a.63011 -
Neurology India 2022Coffin-Siris syndrome (CSS) (OMIM #135900) involves multiple congenital malformations, including hypotonia, short stature, sparse scalp hair, a coarse face, prominent...
Coffin-Siris syndrome (CSS) (OMIM #135900) involves multiple congenital malformations, including hypotonia, short stature, sparse scalp hair, a coarse face, prominent eyebrows, a wide mouth, delayed bone age, and hypoplastic or absent fifth fingers/toes or nails, together with developmental delay. The cause of CSS is suggested to be related to alterations in the BRG- or HRBM-associated factor (BAF) pathway in humans. In this gene family, pathogenic variations in the AT-rich interactive domain-containing protein 1B (ARID1B) gene are revealed to be a significant element causing neurodevelopmental disability in patients with CSS. Herein, we describe the clinical features and gene variations in four Chinese patients with CSS. All the patients shared common features of short fifth fingers/toes or hypoplastic nails, coarse facial features, thick eyebrows, long cilia, a flat nasal bridge, a broad nose, a wide mouth, a high palate, and hypotonia. Besides, they had an intellectual disability, language, and motor developmental delay. Candidate genes were screened for variations using polymerase chain reaction (PCR) and sequencing. The variations were sequenced by next-generation sequencing and confirmed by first-generation sequencing. Exome sequencing suggested four de novo variations in the ARID1B gene in four unrelated patients. These included two frameshift variations (c.3581delC, c.6661_6662insG) and two nonsense variations (c.1936C>T, c.2248C>T). Of the four variations, three variations were novel. The results in our present study broaden the understanding of the disease and further interpret the molecular genetic mechanism of these rare variations in CSS.
Topics: Humans; DNA-Binding Proteins; Muscle Hypotonia; Micrognathism; Hand Deformities, Congenital; Intellectual Disability; Transcription Factors
PubMed: 36352633
DOI: 10.4103/0028-3886.359283