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JA Clinical Reports Jul 2020Schwartz-Jampel syndrome (SJS) is a very rare inherited disorder characterized by multiple skeletal deformities, limited joint mobility, micrognathia, blepharophimosis,...
BACKGROUND
Schwartz-Jampel syndrome (SJS) is a very rare inherited disorder characterized by multiple skeletal deformities, limited joint mobility, micrognathia, blepharophimosis, myotonia, and growth retardation. SJS is caused by mutations in the gene encoding perlecan (heparan sulfate proteoglycan). Anesthetic management of these patients is challenging. The use of spinal anesthesia in these patients has not been reported.
CASE PRESENTATION
A 14-year-old boy was scheduled for inguinal hernia and hydrocele repair. The diagnosis of SJS was based on his dysmorphic features, electromyographic (EMG) pattern and genetic testing. General anesthesia may encounter difficult airway management, resistance to muscle relaxants, or possibility of malignant hyperthermia. Regional anesthesia may be difficult or even harmful due to skeletal deformities. We report successful management of spinal anesthesia and surgery was done. The patient had an uneventful recovery and was discharged home. We describe the special precautions against pitfalls for using this technique in patients with SJS.
CONCLUSION
Spinal anesthesia may be an effective and safe technique for patients with SJS and it may.
PubMed: 32648012
DOI: 10.1186/s40981-020-00357-0 -
Indian Journal of Ophthalmology 2012The purpose of this study was to report the functional and cosmetic outcome of single stage surgical procedure for correction of the classic components of... (Comparative Study)
Comparative Study
PURPOSE
The purpose of this study was to report the functional and cosmetic outcome of single stage surgical procedure for correction of the classic components of Blepharophimosis syndrome.
MATERIALS AND METHODS
We report a retrospective case file review of 11 patients with Blepharophimosis syndrome operated between July 2004 and April 2008. Each patient had undergone the correction of epicanthus inversus, telecanthus, palpebral phimosis, and bilateral ptosis as a single-stage surgical procedure. Patients were examined and photographed before and after surgery. The mean follow-up was 3 years (range 2-6 years).
RESULTS
A total of 11 patients (8 males, 3 females) with a mean age of 9 years (range 6--22 years) were reviewed. The surgical outcome was assessed both functionally and cosmetically. The mean preoperative visual acuity was 0.729 ± 0.316 SD and the mean postoperative visual acuity was 0.856 ± 0.277 SD (P <0.0428). There was a statistically significant decrease of astigmatism following ptosis correction (P<0.05), improvement of telecanthus (P<0.0001) in terms of IICD (inner intercanthal distance), and HPFL (horizontal palpebral fissure length) (P=0.019) along with improvement of the superior visual field. The mean preoperative and postoperative IICD was 3±0.33 SD and 2.418 ± 0.189 SD, respectively. There was also a significant postoperative improvement of ptosis (P< 0.01), as measured by IPFH (vertical interpalpebral fissure height). All the patients had a stable functional and cosmetic result after a mean follow-up period of 3 years.
CONCLUSION
Single-stage surgical correction of the classic anomalies of Blepharophimosis syndrome provides stable and successful long-term results.
Topics: Adolescent; Blepharophimosis; Blepharoplasty; Child; Eyelids; Female; Follow-Up Studies; Humans; Male; Postoperative Period; Retrospective Studies; Syndrome; Time Factors; Treatment Outcome; Visual Acuity; Young Adult
PubMed: 22569380
DOI: 10.4103/0301-4738.95870 -
Indian Journal of Dermatology 2021
PubMed: 33911305
DOI: 10.4103/ijd.IJD_184_19 -
Molecular Genetics & Genomic Medicine Dec 2023Say-Barber-Biesecker-Young-Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in...
BACKGROUND
Say-Barber-Biesecker-Young-Simpson (SBBYSS) variant of Ohdo syndrome is a rare, autosomal dominant and clinically heterogenous disorder, caused by pathogenic variants in the KAT6B gene located on chromosome 10q22.2. KAT6B encodes a highly conserved histone acetyltransferase belonging to the MYST family. Currently, diseases caused by pathogenic variants in KAT6B (KAT6B-related disorders) comprise two allelic entities: SBBYSS variant of Ohdo syndrome and genitopatellar syndrome (GPS). Increase in the number of cases with overlapping GPS/SBBYSS phenotype which makes it necessary to redefine this group of phenotypes as KAT6B-related disorders or KAT6B spectrum disorders. Individuals with SBBYSS usually present with facial abnormalities, hypotonia, joint laxity, feeding problems, and long thumbs/great toes. This syndrome also typically involves skeletal problems including patellar hypoplasia/agenesis.
METHODS
Here we report six SBBYS syndrome patients with the same dysmorphic features but a different course of the disease. One known and five novel KATB6 pathogenic variants were identified by molecular diagnostics using Next Generation Sequencing (NGS).
RESULTS
We present a detailed phenotypic analysis of six individuals with KAT6B-related disorders, in whom a heterozygous pathogenic variant in KAT6B gene was found. In all of our patients facial dysmorphism as well as developmental and speech delay were present. Additionally, all but one patients presented with hypotonia, ocular abnormalities and long thumbs. Most of our probands showed blepharophimosis and skeletal (mainly knee) defects. Contrary to previously reported severe patellar defects (hypoplasia/agenesis) anomalies presented by our patients were less severe (dysplasia, habitual dislocation, subluxation) referring to KAT6B-related disorders.
CONCLUSION
While most of the anomalies found in our patients comply with SBBYSS criteria, phenotypic differences in our probands support a broader spectrum of the disease phenotype. To establish the range of this spectrum, a detailed analysis of clinical variability among patients with SBBYSS requires further investigation.
Topics: Male; Humans; Mutation; Muscle Hypotonia; Poland; Intellectual Disability; Histone Acetyltransferases
PubMed: 37658610
DOI: 10.1002/mgg3.2265 -
Ceska a Slovenska Oftalmologie :... 2016Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to... (Review)
Review
OBJECTIVE
Preimplantation genetic diagnosis (PGD) is an established application of genetic testing in the context of in vitro fertilization. PGD is an alternative method to prenatal diagnosis which aims to prevent the transmission of an inherited disorder to the progeny by implanting only embryos that do not carry genetic predisposition for a particular disease. The aim of this study is to provide an overview of eye disorders for which PGD has been carried out.
METHODS
The European literature search focused on best practices, ethical issues, risks and results of PGD for inherited eye disorders.
RESULTS
PGD is performed for a number of ocular disorders; a prerequisite for its application is however, the knowledge of a disease-causing mutation(s). The main advantage of this method is that the couple is not exposed to a decision of whether or not to undergo an abortion. Qualified counselling must be provided prior to the PGD in order to completely understand the risk of disability in any child conceived, consequences of disease manifestation, and advantages as well as limitations of this method. In the group of non-syndromic eye diseases and diseases in which ocular findings dominate, PGD has been performed in European countries for aniridia, choroideremia, congenital fibrosis of extraocular muscles, Leber congenital amaurosis, ocular albinism, retinitis pigmentosa, X-linked retinoschisis, Stargardt disease, blepharophimosis-ptosis-inverse epicanthus syndrome and retinoblastoma. Sexing for X-linked or mitochondrial diseases has been carried out for blue cone monochromatism, choroideremia, familial exudative vitreoretinopathy, Leber hereditary optic neuropathy, macular dystrophy (not further specified), Norrie disease, X-linked congenital stationary night blindness, X-linked retinoschisis and nystagmus (not further specified).
CONCLUSION
In recent years, there has been an increase in potential to use PGD. The spectrum of diseases for this method has widened to include severe inherited eye diseases.Key words: preimplantation genetic diagnosis; monogenic eye diseases; in vitro fertilization.
Topics: Eye Diseases, Hereditary; Eye Neoplasms; Female; Fertilization in Vitro; Genetic Predisposition to Disease; Genetic Testing; Humans; Male; Pregnancy; Preimplantation Diagnosis; Prenatal Diagnosis
PubMed: 28224801
DOI: No ID Found -
International Journal of Molecular... 2023Turner-type X-linked syndromic intellectual developmental disorder (MRXST) is a rare neurodevelopmental disorder. MRXST is caused by pathogenic variants in the gene on... (Review)
Review
Turner-type X-linked syndromic intellectual developmental disorder (MRXST) is a rare neurodevelopmental disorder. MRXST is caused by pathogenic variants in the gene on chromosome Xp11.22. The gene encodes a ubiquitin ligase, which has downstream effects on the n-MYC protein and DLL3 Notch ligand, ultimately affecting neuronal differentiation. In addition to intellectual disability and developmental delay, other clinical features such as absent or delayed speech, skeletal abnormalities, abnormalities in hands or feet, seizures, and hypotonia have been described in case reports. Facial dysmorphic features and eye manifestations have been reported in patients with MRXST, but have not been identified as distinctive to this condition. We report two cases of individuals affected by -Related Intellectual Developmental Disorder and present a review of literature of male patients affected by this disorder. Based on the literature review and findings in our two patients, it is our observation that patients with MRXST present with distinctive features, which include broad nasal tip, root, or prominent nose (39%), blepharophimosis (27%), epicanthic folds (25%), ear abnormalities (25%), thin upper lip (23%), and deep set eyes (23%). Furthermore, we note that oculofacial abnormalities are seen more frequently in patients with missense variants than patients with duplications in the gene. The findings noted in this paper may help clinicians suspect a diagnosis of MRXST when presented with these distinctive ocular and facial features.
PubMed: 38021253
DOI: No ID Found -
BMJ Case Reports Jul 2017Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS), also known as Ohdo syndrome SBBYS type, is a rare genetic disorder characterised by dysmorphic facial features and...
Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS), also known as Ohdo syndrome SBBYS type, is a rare genetic disorder characterised by dysmorphic facial features and severe intellectual disability, as well as cardiac, dental and hearing abnormalities. There has been little psychiatric or psychological description of children with SBBYSS, although previous reports noted repetitive self-injurious behaviours, sensitivity to light and noise and severe deficits in communication. In this report, a 4-year-old male with SBBYSS is described with a focus on psychiatric and psychological assessment, including formal testing for autism spectrum disorder (ASD). Results of multiple behavioural assessment scales are reported. Testing revealed characteristic ASD features, and the patient met criteria for ASD diagnosis in the context of SBBYSS. His behaviours improved with Applied Behavioural Analysis therapy and communication skills training. This is the first documented case of ASD reported alongside SBBYSS. These results suggest ASD may be a clinical feature of SBBYSS.
Topics: Autism Spectrum Disorder; Blepharophimosis; Child, Preschool; Congenital Hypothyroidism; Diagnosis, Differential; Facies; Heart Defects, Congenital; Humans; Intellectual Disability; Joint Instability; Male; Self-Injurious Behavior
PubMed: 28710305
DOI: 10.1136/bcr-2017-219930 -
Human Mutation Nov 2012Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) have both recently been shown to be caused by distinct mutations... (Comparative Study)
Comparative Study Review
Genitopatellar syndrome (GPS) and Say-Barber-Biesecker-Young-Simpson syndrome (SBBYSS or Ohdo syndrome) have both recently been shown to be caused by distinct mutations in the histone acetyltransferase KAT6B (a.k.a. MYST4/MORF). All variants are de novo dominant mutations that lead to protein truncation. Mutations leading to GPS occur in the proximal portion of the last exon and lead to the expression of a protein without a C-terminal domain. Mutations leading to SBBYSS occur either throughout the gene, leading to nonsense-mediated decay, or more distally in the last exon. Features present only in GPS are contractures, anomalies of the spine, ribs and pelvis, renal cysts, hydronephrosis, and agenesis of the corpus callosum. Features present only in SBBYSS include long thumbs and long great toes and lacrimal duct abnormalities. Several features occur in both, such as intellectual disability, congenital heart defects, and genital and patellar anomalies. We propose that haploinsufficiency or loss of a function mediated by the C-terminal domain causes the common features, whereas gain-of-function activities would explain the features unique to GPS. Further molecular studies and the compilation of mutations in a database for genotype-phenotype correlations (www.LOVD.nl/KAT6B) might help tease out answers to these questions and understand the developmental programs dysregulated by the different truncations.
Topics: Abnormalities, Multiple; Base Sequence; Blepharophimosis; Blepharoptosis; Craniofacial Abnormalities; DNA; Databases, Nucleic Acid; Female; Genetic Association Studies; Haploinsufficiency; Heart Defects, Congenital; Histone Acetyltransferases; Humans; Intellectual Disability; Kidney; Male; Molecular Sequence Data; Mutation; Patella; Psychomotor Disorders; Scrotum; Sequence Deletion; Urogenital Abnormalities
PubMed: 22715153
DOI: 10.1002/humu.22141 -
Journal of Clinical and Diagnostic... Mar 2017Blepharophimosis Syndrome (BPES) is a complex and rare disease characterized by epicanthus inversus, telecanthus, lateral ectropion, narrowed or shortened...
INTRODUCTION
Blepharophimosis Syndrome (BPES) is a complex and rare disease characterized by epicanthus inversus, telecanthus, lateral ectropion, narrowed or shortened inter-palpebral fissure distance and ptosis. It is mostly bilateral and may or may not be symmetrical. It is typically inherited as an autosomal dominant trait. In sporadic cases, the disease may occur without a prior family history as a genetic mutation from a deletion or translocation of the gene, which maps to chromosome 3q23. Surgical treatment of this disease poses an oculoplastic challenge due to multiple complex eyelid deformities.
AIM
To evaluate the functional and cosmetic outcome of telecanthus and epicanthus correction by a Mustarde's rectangular double Z-Plasty and trans-nasal fixation using 1-0 prolene suture in BPES.
MATERIALS AND METHODS
This was prospective, interventional study of 16 patients over a period of three years. In this study, all patients had BPES with prominent epicanthus and telecanthus. Mustarde's double Z-plasty and trans-nasal fixation with 1-0 prolene suture was performed in the first of a two-stage operation. If ectropion was present, the lateral ectropion was corrected by a base-out flap transfer from the upper eyelid to the lower eyelid. After three months, a 2 stage was undertaken, involving a lateral canthoplasty for horizontal widening of a short palpebral fissure and a tarso frontalis sling with silicone rod for correction of moderate to severe ptosis. Patients were followed up for six months to one year with postoperative ophthalmologic examinations and photographs.
RESULTS
Out of 16 patients, 10 were females and six were males. All the patients had bilateral involvement. In this study preoperative Inner Intercanthal Distance (IICD) ranged from 38 mm to 42 mm and the mean IICD was 41.2±0.57 mm. Postoperative IICD ranged from 31 mm to 34 mm. Horizontal Palpebral Fissure Length (HPFL) ranged from 20 mm to 23 mm and the mean value of HPFL was 21.50 mm preoperatively. Postoperative HPFL ranged from 26 mm to 29 mm and had a mean value of 28.50 mm, which was much improved after a combined correction of telecanthus and lateral canthoplasty. The mean preoperative IICD and HPFL ratio was 1.77 and was reduced to a postoperative value of 1.2. The Marginal Reflex Distance1 (MRD-1) test value improved from +1.25 mm to +3.50 mm postoperatively after placement of a tarsofrontalis sling with silicone rod using the Fox's Pentagon technique. In this study, two eyes had minimal unequal correction but were cosmetically and functionally acceptable. Correction of IICD is possible up to 6 mm. No major complication e.g., CSF rhinorrhea was noted in this series and preoperative prominent epicanthal folds were abolished.
CONCLUSION
Here we propose a two-staged procedure involving a combined Mustarde's double Z-plasty with transnasal fixation using a 1-0 prolene suture with a flap transfer from the upper lid to the lower lid in the first stage and a lateral canthoplasty with a tarsofrontalis sling and silicone rod in the second stage. This technique is effective to correct epicanthus, telecanthus, ptosis and lateral ectropion in BPES with good cosmetic and functional outcome.
PubMed: 28511421
DOI: 10.7860/JCDR/2017/25651.9496 -
Journal of Ovarian Research Oct 2021FOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES... (Review)
Review
BACKGROUND
FOXL2 mutations in human cause Blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). While type II BPES solely features eyelid abnormality, type I BPES involves not only eyelid but also ovary, leading to primary ovarian insufficiency (POI) and female infertility. Current mainstream reproductive option for type I BPES is embryo or oocyte donation. Attempts on assisted reproductive technology (ART) aiming biological parenthood in this population were sparse and mostly unsuccessful.
CASE PRESENTATION
Two Chinese type I BPES patients with low anti-müllerian hormone (AMH) and elevated follicle stimulating hormone (FSH) presented with primary infertility in their early 30s. Genetic studies confirmed two heterozygous duplication mutations that were never reported previously in East Asian populations. They received in vitro fertilization (IVF) treatment and both exhibited resistance to gonadotropin and difficulty in retrieving oocytes in repeated cycles. Doubled to quadrupled total gonadotropin doses were required to awaken follicular response. Patient 1 delivered a baby girl with the same eyelid phenotype and patient 2 had ongoing live intrauterine pregnancy at the time of manuscript submission.
CONCLUSIONS
This is the second reported live birth of biological offspring in type I BPES patients, and first success using IVF techniques. It confirmed that ART is difficult but feasible in type I BPES. It further alerts clinicians and genetic counsellors to type female BPES patients with caution in view of the precious and potentially narrowed reproductive window.
Topics: Adult; Female; Fertilization in Vitro; Gonadotropins; Humans; Oocyte Retrieval
PubMed: 34711234
DOI: 10.1186/s13048-021-00900-2