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Neurology India 2023We report a 24-year-old male with blepharophimosis, psychomotor retardation, brachycephaly, microstomia, immobile face, high arched palate, single palmar crease,...
We report a 24-year-old male with blepharophimosis, psychomotor retardation, brachycephaly, microstomia, immobile face, high arched palate, single palmar crease, kyphoscoliosis, talipes equinovarus, inguinal hernia, pyloric stenosis, recurrent infections, bilateral camptodactyly, wide-set eyes, decreased muscle mass, hypotonia, exotropia, and ptosis in the left eye, growth retardation, multiple congenital contractures, and hyporreflexia. Contractures improved with aging, but intellectual disability and blepharophimosis remained. He also presented epilepsy, outbursts of laughter, and predisposition to drug adverse effects (skin lesions with carbamazepine and secondary parkinsonism).
Topics: Male; Humans; Young Adult; Adult; Blepharophimosis; Syndrome; Abnormalities, Multiple; Contracture; Intellectual Disability
PubMed: 37635513
DOI: 10.4103/0028-3886.383870 -
Medicine Apr 2020Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we...
RATIONALE
Wiedemann-Steiner syndrome (WDSTS, online mendelian inheritance in man 605130) is a rare autosomal dominant disorder characterized by hypertrichosis cubiti. Here, we report a Chinese boy who do not show the characteristic of hypertrichosis cubiti, and was misdiagnosed as blepharophimosis-ptosis-epicanthus inversus syndrome at first. We found a de novo frameshift mutation (p.Glu390Lysfs*10) in the KMT2A gene, which was not reported before. Our study increases the cohort of Chinese WDSTS patients, and expand the WDSTS phenotypic and variation spectrum.
PATIENT CONCERNS
The patient demonstrated typical craniofacial features of blepharophimosis-ptosis-epicanthus inversus syndrome, including small palpebral fissures, ptosis, telecanthus, and epicanthus inversus, besides he had congenital heart disease (ventricular septal defects), strabismus, hypotonia, amblyopia, delayed speech and language development, delayed psychomotor development, and amblyopia (HP:0000646) which was not reported before.
DIAGNOSIS
FOXL2 gene was cloned and sequenced, however, there was no mutation detected in this patient. The result of Chromosomal microarray analysis was normal. The patient was diagnosed as WDSTS by whole exome sequencing.
INTERVENTIONS
The patient received cardiac surgery, frontalis suspension and regular speech and occupational therapy. He also treated with growth hormone (GH).
OUTCOMES
The patient's symptoms are improved after cardiac surgery and frontalis suspension, he can express himself well now and had a 10 cm gain in height.
LESSONS
As the relationship between genotype and phenotype becomes more and more clear, WES is incredibly powerful tool to diagnose the disease of WDSTS.
Topics: Abnormalities, Multiple; Asian People; Blepharophimosis; Child; Contracture; Diagnostic Errors; Facies; Genotype; Growth Disorders; Growth Hormone; Heart Defects, Congenital; Histone-Lysine N-Methyltransferase; Humans; Hypertrichosis; Intellectual Disability; Male; Microcephaly; Mutation; Myeloid-Lymphoid Leukemia Protein; Phenotype; Skin Abnormalities; Treatment Outcome; Urogenital Abnormalities; Exome Sequencing
PubMed: 32311999
DOI: 10.1097/MD.0000000000019813 -
European Journal of Human Genetics :... Oct 2022The pituitary gland, as a nodal component of the endocrine system, is responsible for the regulation of growth, reproduction, metabolism, and homeostasis. Although...
The pituitary gland, as a nodal component of the endocrine system, is responsible for the regulation of growth, reproduction, metabolism, and homeostasis. Although pituitary formation though the hierarchical action of different transcription factors is well studied in mouse models, there is little evidence of the analogous developmental processes in humans. Herein, we present a female patient with a phenotype that includes blepharoptosis-ptosis-epicanthus syndrome and premature ovarian failure. Clinical exome sequencing revealed two heterozygous variants in two genes, LHX4 (pathogenic) and NR5A1 (VUS) genes and no mutation in FOXL2 gene. We propose a model of genetic interaction between LHX4 and NR5A1 during pituitary and ovarian development that may lead to a similar phenotype mediated by reduced FOXL2 expression.
Topics: Animals; Blepharophimosis; Female; Forkhead Transcription Factors; Genes, Developmental; Humans; LIM-Homeodomain Proteins; Mice; Pituitary Gland; Primary Ovarian Insufficiency; Steroidogenic Factor 1; Transcription Factors
PubMed: 35277652
DOI: 10.1038/s41431-022-01076-z -
F&S Reports Sep 2021To describe the experiences of three women with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) who desired to pursue planned oocyte cryopreservation.
OBJECTIVE
To describe the experiences of three women with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) who desired to pursue planned oocyte cryopreservation.
DESIGN
Case series.
SETTING
An academic institution and a private clinic.
PATIENTS
Three nulligravid women aged 23, 25, and 34 years who desired to pursue planned oocyte cryopreservation. Two women had BPES diagnosed when they were infants and one had BPES diagnosed after presenting to discuss oocyte cryopreservation.
INTERVENTIONS
All three women underwent ovarian stimulation. One woman underwent three oocyte retrievals.
MAIN OUTCOMES MEASURES
Vitrification of metaphase II oocytes.
RESULTS
One woman had a total of eight metaphase II oocytes vitrified. In addition, she underwent genetic testing that confirmed type 1 BPES. The other two women, who had BPES diagnosed when they were newborns, each underwent two cycles of ovarian stimulation. Neither of these two women responded to ovarian stimulation and both cycles were cancelled before oocyte retrieval.
CONCLUSIONS
BPES is a rare condition that can lead to primary ovarian insufficiency. Early identification of this condition is important to allow for timely reproductive counseling so that oocyte cryopreservation can be offered at a young age before oocyte depletion. Careful counseling is critical for these patients, because this case series demonstrated that not all women with BPES will respond to stimulation. Further, outcomes with cryopreserved oocytes have not yet been described in women with BPES.
PubMed: 34553160
DOI: 10.1016/j.xfre.2021.05.006 -
International Journal of Clinical and... 2014FOXL2 is a transcription factor that is essential for ovarian function and maintenance, the germline mutations of which give rise to the blepharophimosis ptosis...
FOXL2 is a transcription factor that is essential for ovarian function and maintenance, the germline mutations of which give rise to the blepharophimosis ptosis epicanthus inversus syndrome (BPES), often associated with premature ovarian failure. Recently, its mutations have been found in ovarian granulosa cell tumors (OGCTs). In this study, we measured the expression of FOXL2 in cervical cancer by immunohistochemistry and its mRNA level in cervical cancer cell lines Hela and Siha by RT-PCR. Then we overexpressed FOXL2 in Hela cells and silenced it in Siha cells by plasmid transfection and verified using western blotting. When FOXL2 was overexpressed or silenced, cells proliferation and apoptosis were determined by Brdu assay and Annexin V/PI detection kit, respectively. In addition, we investigated the effects of FOXL2 on the adhesion and invasion of Hela and Siha cells. Finally, we analyzed the influences of FOXL2 on Ki67, PCNA and FasL by flow cytometry. The results showed that FOXL2 was highly expressed in cervical squamous cancer. Overexpressing FOXL2 suppressed Hela proliferation and facilitated its apoptosis. Silencing FOXL2 enhanced Siha proliferation and inhibited its apoptosis. Meanwhile, silencing FOXL2 promoted Siha invasion, but it had no effect on cells adhesion. In addition, overexpressing FOXL2 decreased the expression of Ki67 in Hela and Siha cells. Therefore, our results suggested that FOXL2 restrained cells proliferation and enhanced cells apoptosis mainly through decreasing Ki67 expression.
Topics: Adenocarcinoma; Adult; Apoptosis; Carcinoma, Squamous Cell; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cells, Cultured; Fas Ligand Protein; Female; Forkhead Box Protein L2; Forkhead Transcription Factors; Gene Expression Regulation, Neoplastic; Gene Silencing; HeLa Cells; Humans; Ki-67 Antigen; Middle Aged; Proliferating Cell Nuclear Antigen; Uterine Cervical Neoplasms
PubMed: 24817949
DOI: No ID Found -
Taiwanese Journal of Obstetrics &... May 2022To precision survey a fetal congenital primary aphakia molecular etiology.
OBJECTIVE
To precision survey a fetal congenital primary aphakia molecular etiology.
CASE REPORT
A case of 42 years old pregnancy woman prenatal diagnostic examination by amniocentesis conducted at 17 weeks' gestation and demonstrated a normal female karyotype. Trio studies based on chromosome microarray analysis (CMA) and Sanger's genetic analysis did not detect a pathologic variant of the FOXE3 gene. Fetal congenital primary aphakia accompanied with microphthalmia detected by sonography in the second trimester (22 weeks). MRI indicated bilateral absence of the lenses, consistent with primary congenital aphakia. Due to the poor prognosis of congenital aphakia, the parents decided to terminate the fetus and provided consent for an autopsy. Pathological analysis revealed dysplasia of the anterior segment of both eyes. However, post fetal mortem extended trio whole exon sequencing (WES) and Sanger's genetic analysis identified compound heterozygous variants in the chromosomal location 2p25.3 in the PXDN gene.
CONCLUSION
Extended whole exon sequencing is an important tool to study primary congenital aphakia.
Topics: Adult; Aphakia; Blepharophimosis; Deoxyribonucleosides; Eye Abnormalities; Female; Fetus; Humans; Pregnancy; Prenatal Diagnosis; Purine Nucleosides
PubMed: 35595447
DOI: 10.1016/j.tjog.2022.03.019 -
Taiwan Journal of Ophthalmology 2022The purpose of this study was to describe the single-triangle technique for congenital ptosis repair with a frontalis sling in blepharophimosis patients. The...
The purpose of this study was to describe the single-triangle technique for congenital ptosis repair with a frontalis sling in blepharophimosis patients. The single-triangle technique was used in 40 eyes of 20 patients of blepharophimosis syndrome. The center point of the lid is marked. The desired base length is calculated depending on the available horizontal fissure width. Two marks are inked 2 mm above the lid margin, equidistant from the central mark. A single brow mark is placed in such a way that it is directly above the center point of the lid. These are now joined to complete the triangle. In blepharophimosis patients, the mean preoperative margin reflex distance (MRD1) was 1.0 ± 1.1 mm which increased to 4.1 ± 1.6 mm after surgery. The MRD1 increased by 3.1 ± 1.7 mm. Cosmetic outcome was graded with a score of 0, 1, or 2 to indicate poor, good, and excellent results, respectively. Out of the 40 eyes that were operated, 33 eyes had a score of 2, 5 eyes had a score of 1, and 2 eyes were scored 0. The single-triangle technique has several advantages over both the Fox pentagon technique and modified Crawford technique in severe blepharophimosis patients. It is not only a much simpler procedure to perform but also has a better control over the curvature of the lid without any central focal notching, thus providing better cosmesis and esthetic results.
PubMed: 35399970
DOI: 10.4103/tjo.tjo_6_21 -
The Journal of Biological Chemistry Mar 2009Follistatin is a transcriptional target and a modulator of activin action. Through an autocrine/paracrine loop, activin controls follistatin levels and thus regulates...
Follistatin is a transcriptional target and a modulator of activin action. Through an autocrine/paracrine loop, activin controls follistatin levels and thus regulates its own bioavailability. In gonadotropic alphaT3-1 cells, activin induces follistatin transcription primarily through the action of Smad3 at an intronic Smad-binding element (SBE1). Using a proteomics approach, we searched for endogenous alphaT3-1 proteins that participate in SBE1-mediated transcription. We identified FoxL2, a member of the forkhead family, as a candidate modulator of SBE1 function. Mutations of FoxL2 are associated with the blepharophimosis/ptosis/epicanthus inversus syndrome characterized with craniofacial defects and premature ovarian failure. FoxL2 localizes to alpha-glycoprotein subunit- and follicle-stimulating hormone beta-positive cells of the adult mouse pituitary and is present in alphaT3-1 and LbetaT2 cells, but its pituitary actions remain largely unknown. We have determined that FoxL2 binds to a forkhead-binding element (FKHB) located just downstream of the SBE1 site of the follistatin gene and functions as a Smad3 partner to drive SBE1-mediated transcription in alphaT3-1 cells treated with activin. Chromatin immunoprecipitation assays confirm that endogenous FoxL2 and Smad3 are recruited to the intronic enhancer of the follistatin gene where the SBE1 and FKHB sites are located. Exogenous FoxL2 enhances SBE1-mediated transcription, and short hairpin RNA-mediated knockdown of endogenous FoxL2 protein compromises this effect in alphaT3-1 cells. FoxL2 directly associates with Smad3 but not Smad2 or Smad4. This association between Smad3 and FoxL2 is mediated by the MH2 domain of Smad3 and is dependent on an intact forkhead domain in FoxL2. Altogether, these observations highlight a novel role for FoxL2 and suggest that it may function as a transcriptional regulator and a coordinator of Smad3 targets.
Topics: Activins; Animals; Blepharoptosis; Cell Line; Follistatin; Forkhead Box Protein L2; Forkhead Transcription Factors; Humans; Introns; Mice; Mice, Knockout; Mutation; Pituitary Gland; Response Elements; Smad3 Protein; Transcription, Genetic
PubMed: 19106105
DOI: 10.1074/jbc.M806676200 -
Human Genome Variation 2015The mediator complex subunit 12 gene (MED12) is responsible for an X-linked recessive intellectual disability syndrome that is characterized by dysmorphic features such...
The mediator complex subunit 12 gene (MED12) is responsible for an X-linked recessive intellectual disability syndrome that is characterized by dysmorphic features such as a long, narrow face and blepharophimosis, which is now recognized as an MED12-related syndrome. We identified a novel non-synonymous single-nucleotide variant, p.Ile1023Val, in a male patient with non-specific X-linked intellectual disability (XLID). Our results, together with the existence of similar reports, suggest a relationship between MED12 variants and XLID.
PubMed: 27081531
DOI: 10.1038/hgv.2015.18 -
Indian Journal of Ophthalmology Sep 2014A 2-year 7-month-old girl born out of a consanguineous marriage, presented at our facility with clinical features characterized by the eyelid triad of blepharophimosis,... (Review)
Review
A 2-year 7-month-old girl born out of a consanguineous marriage, presented at our facility with clinical features characterized by the eyelid triad of blepharophimosis, blepharoptosis and epicanthus inversus in association with hypertelorism, cleft palate and craniosynostosis. This constellation of features is suggestive of Michels syndrome. At the time of writing this report, there were only ten reported cases worldwide and to the best of our knowledge, there have been no published reports from India.
Topics: Child, Preschool; Craniosynostoses; Esotropia; Eye Abnormalities; Eye Movements; Female; Humans; India; Visual Acuity
PubMed: 25370402
DOI: 10.4103/0301-4738.143946