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The Journal of Craniofacial SurgeryBlepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the...
Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) is a relatively uncommon autosomal-dominant genetic disorder, primarily attributed to mutations in the forkhead box L2 (FOXL2) gene. Albeit the involvement of protein-coding regions of FOXL2 has been observed in the majority of BPES cases, whether deficiencies in regulatory elements lead to the pathogenesis remains poorly understood. Herein, an autosomal-dominant BPES type II family was included. Peripheral venous blood has been collected, and genomic DNA has been extracted from leukocytes. A whole exome sequencing analysis has been performed and analyzed (Deposited in NODE database: OER422653). The promoter region of FOXL2 was amplified using polymerase chain reaction (PCR). The luciferase reporter assay was performed to identify the activity of this region. In this study, we present a Chinese family diagnosed with type II BPES, characterized by the presence of small palpebral fissures, ptosis, telecanthus, and epicanthus inversus. Notably, all male individuals within the family display polydactyly. A 225-bp deletion in the 556-bp 5'-upstream to transcription start site of FOXL2 , decorated by multiple histone modifications, was identified in affected members of the family. This deletion significantly decreased FOXL2 promoter activity, as measured by the luciferase assay. Conclusively, a novel 255-bp-deletion of the FOXL2 promoter was identified in Chinese families with BPES. Our results expand the spectrum of known FOXL2 mutations and provide additional insight into the genotype-phenotype relationships of the BPES pathogenesis. In addition, this study indicates the important role of genetic screening of cis-regulatory elements in testing heritable diseases.
Topics: Humans; Male; Forkhead Box Protein L2; Blepharophimosis; Pedigree; Blepharoptosis; Mutation; Promoter Regions, Genetic; China; Luciferases; Skin Abnormalities; Urogenital Abnormalities
PubMed: 37938073
DOI: 10.1097/SCS.0000000000009801 -
Neurology India 2023
Topics: Child; Humans; Polydactyly; Seizures
PubMed: 37929493
DOI: 10.4103/0028-3886.388066 -
Cureus Oct 2023Trisomy 13 (T13), frequently referred to as Patau syndrome, is a rare autosomal aneuploidy most commonly due to nondisjunction in meiosis. Frequently seen...
Trisomy 13 (T13), frequently referred to as Patau syndrome, is a rare autosomal aneuploidy most commonly due to nondisjunction in meiosis. Frequently seen characteristics include cleft lip, cleft palate, cerebral defects, anophthalmia, and polydactyly among many more. We report a rare case of a newborn female with T13, demonstrating several known anomalies associated with the syndrome and an associated large congenital hepatic cyst, exhibiting a significant mass effect on vital organs. Based on a literature review conducted in August 2023, we found no previous documentation of a congenital hepatic cyst reported with T13.
PubMed: 37927679
DOI: 10.7759/cureus.46377 -
Children (Basel, Switzerland) Oct 2023The diagnostic process for children and adults manifesting a constellation of ectodermal abnormalities requires a conscientious and highly structured process.
BACKGROUND
The diagnostic process for children and adults manifesting a constellation of ectodermal abnormalities requires a conscientious and highly structured process.
MATERIAL AND METHODS
Six girls (aged 6-month-8 years) and two older girls (aged 13 and 16 years) were born with variable skin lesions of varying intensities associated with noticeable cranial and skeletal malformation complexes. Cleft palate, abnormal dentition, and multiple papillomas were evident around the mouth, mostly bilateral but asymmetrical in the upper and lower limbs. Exaggerated frontal bossing (macrocephaly) and in some patients' microcephaly with variable skeletal defects of the craniocervical junction and diverse forms of lower limb deformities of syndactyly, polydactyly, and split-hand/foot (ectrodactyly).
RESULTS
All patients manifested the constellation of abnormalities with variable intensities ranging between alopecia, papillomas, striated skin pigmentations split-hand/foot (ectrodactyly), and major bone defects. A 3D reconstruction CT scan was directed mainly to further scrutinize children with pseudo cleft lip, submucus cleft, and cleft palate. Interstingly, they manifested massive demineralization of the cranium associated with severely defective dentition. A spine 3D reconstruction CT scan in two girls showed marked cystic cavitation of the upper jaw associated with excessive cavitation of the mastoid, causing tremendous frailty of the mastoid bone. A 3D sagittal CT scan showed odontoid hypoplasia and C1-2 instability associated with the rudimentary atlas and the persistence of extensive synchondrosis of the cervico-thoracic spine. The overall clinical and radiological phenotypic characterizations were consistent with the diagnosis of focal dermal hypoplasia (Goltz syndrome). Two children manifested heterozygous mutations in the PORCN gene, chromosome Xp11.
CONCLUSIONS
In this study, we believe it's a good opportunity to share our novel scientific findings, which are intriguing and can be inspiring to readers, and to further aid the current scientific literature with exceptionally new unveiling results. This is the first comprehensive study of the cranio-skeletal malformation complex in children with GS.
PubMed: 37892378
DOI: 10.3390/children10101715 -
Frontiers in Endocrinology 2023Primary cilia are microtubule-based organelles that are widespread on the cell surface and play a key role in tissue development and homeostasis by sensing and... (Review)
Review
Primary cilia are microtubule-based organelles that are widespread on the cell surface and play a key role in tissue development and homeostasis by sensing and transducing various signaling pathways. The process of intraflagellar transport (IFT), which is propelled by kinesin and dynein motors, plays a crucial role in the formation and functionality of cilia. Abnormalities in the cilia or ciliary transport system often cause a range of clinical conditions collectively known as ciliopathies, which include polydactyly, short ribs, scoliosis, thoracic stenosis and many abnormalities in the bones and cartilage. In this review, we summarize recent findings on the role of primary cilia and ciliary transport systems in bone development, we describe the role of cilia in bone formation, cartilage development and bone resorption, and we summarize advances in the study of primary cilia in fracture healing. In addition, the recent discovery of crosstalk between integrins and primary cilia provides new insights into how primary cilia affect bone.
Topics: Cilia; Flagella; Biological Transport; Kinesins; Dyneins
PubMed: 37886641
DOI: 10.3389/fendo.2023.1259650 -
Case Reports in Genetics 2023There is evidence that neurodevelopmental disorders are associated with chromosomal abnormalities. Current genetic testing can clinch an exact diagnosis in 20-25% of...
INTRODUCTION
There is evidence that neurodevelopmental disorders are associated with chromosomal abnormalities. Current genetic testing can clinch an exact diagnosis in 20-25% of such cases. A 3 years and 11 months old boy with global developmental delay had repetitive behaviors and hyperkinetic movements. He was stunted and underweight. He had ataxia, limb dyskinesia, triangular face, microcephaly, upward slanting palpebral fissure, hypertelorism, retrognathia, posteriorly rotated ears, long philtrum, thin lips, broad nasal tip, polydactyly, tappering fingers, and decreased tone in the upper and lower limbs with normal deep tendon reflexes. Magnetic resonance imaging of the brain, ultrasound of the abdomen, and ophthalmological evaluation were normal. Brain evoked response auditory revealed bilateral moderate hearing loss. He fulfilled the Diagnostic Statistical Manual 5 criteria for autism. In the Vineland Social Maturity Scale, his score indicated a severe delay in social functioning. His genetic evaluation included karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA). The karyotype report from high-resolution lymphocyte cultures was mos 46, XY, der(3)t(3; 5)(p26; p15.3)[50]/46, XY,der(5) t(3;5) (p26;p15.3)[50].ish. His karyotype report showed a very rare and abnormal mosaic pattern with two cell lines (50% each). Cell-line#1: 3pter deletion with 5pter duplication (3pter-/5pter+) and cell-line#2: 3pter duplication with 5pter deletion (3pter+/5pter-) derived from a reciprocal translocation t(3; 5)(p26; p15.3) which was confirmed by FISH. The chromosomal microarray analysis report was normal. The two cell lines (50% each) seem to have balanced out at the whole genome level. Occupational, sensory integration, and behavior modification therapy were initiated for his autistic features, and anticholinergic trihexiphenidyl was prescribed for hyperkinetic movements.
CONCLUSION
This case highlights a rare genetic finding and the need for timely genetic testing in a child with dysmorphism and autism with movement disorder to enable appropriate management and genetic counselling.
PubMed: 37876589
DOI: 10.1155/2023/7974886 -
Journal of Anatomy Feb 2024The primary cilium is an essential organelle that is important for normal cell signalling during development and homeostasis but its role in pituitary development has...
The primary cilium is an essential organelle that is important for normal cell signalling during development and homeostasis but its role in pituitary development has not been reported. The primary cilium facilitates signal transduction for multiple pathways, the best-characterised being the SHH pathway, which is known to be necessary for correct pituitary gland development. FUZ is a planar cell polarity (PCP) effector that is essential for normal ciliogenesis, where the primary cilia of Fuz mutants are shorter or non-functional. FUZ is part of a group of proteins required for recruiting retrograde intraflagellar transport proteins to the base of the organelle. Previous work has reported ciliopathy phenotypes in Fuz homozygous null mouse mutants, including neural tube defects, craniofacial abnormalities, and polydactyly, alongside PCP defects including kinked/curly tails and heart defects. Interestingly, the pituitary gland was reported to be missing in Fuz mutants at 14.5 dpc but the mechanisms underlying this phenotype were not investigated. Here, we have analysed the pituitary development of Fuz mutants. Histological analyses reveal that Rathke's pouch (RP) is initially induced normally but is not specified and fails to express LHX3, resulting in hypoplasia and apoptosis. Characterisation of SHH signalling reveals reduced pathway activation in Fuz mutant relative to control embryos, leading to deficient specification of anterior pituitary fate. Analyses of the key developmental signals FGF8 and BMP4, which are influenced by SHH, reveal abnormal patterning in the ventral diencephalon, contributing further to abnormal RP development. Taken together, our analyses suggest that primary cilia are required for normal pituitary specification through SHH signalling.
Topics: Animals; Mice; Cell Polarity; Cilia; Hedgehog Proteins; Mice, Knockout; Pituitary Gland; Proteins
PubMed: 37794731
DOI: 10.1111/joa.13961 -
International Journal of Surgery Case... Oct 2023We present a case of Congenital fibular dimelia or fibula duplication with tibial hypoplasia, talar duplication and diplopodia with two complete pre-axial rays. This...
INTRODUCTION AND IMPORTANCE
We present a case of Congenital fibular dimelia or fibula duplication with tibial hypoplasia, talar duplication and diplopodia with two complete pre-axial rays. This association has not been published in the literature to our knowledge. We discuss the unique features and surgical management of this rare condition.
CASE PRESENTATION
The patient is a 3 year old child with congenital unilateral fibular dimelia, tibial hypoplasia, talar duplication and diplopodia who presented to us with leg length discrepancy and progressive equinovarus deformation of the right foot and ankle. She was surgically treated by excision of the medial two rays, cuneiforms, navicular, duplicate talus, os calcis and medial accessory fibula with reconstruction of the ankle joint capsule and foot reconstruction.
DISCUSSION
Due to the rarity of the condition there is no described treatment protocol. It was decided to do resection taking in consideration of the disabling and unsightly progressive deformity.
CONCLUSION
The case presented is a very rare of type of duplication deformity which we believe to be unique. The surgical treatment has been performed due to progressive deformity based on principles of management. Future follow up to observe growth and development of the lower limb joints, especially the ankle, as well as treatment for leg length equalization will be required.
PubMed: 37776687
DOI: 10.1016/j.ijscr.2023.108834