Wolf-Hirschhorn Syndrome Research Articles

Features of translation of pathoanatomical terms-metaphors

The article examines the peculiarities of the Ukrainian-English-Latin translation of pathoanatomical terms-metaphors with a modifier - an adjective formed from the name of the animal, based on the material of the publication "Dorland's English-Ukrainian Illustrated Medical Dictionary" (2002). Many studies by domestic linguists have been devoted to the problem of medical terminological vocabulary. Among the topics that attract the attention of scientists are the historical aspect of the formation and development of medical vocabulary, the vocabulary of individual subsystems, Greek-Latin medical terms, translation transformations in Latin-English and Ukrainian-English translation. Pathological-anatomical terminology remains outside the attention of researchers due to the presence and use in medical practice of "unofficial" terms, or those that have just entered circulation, which is why the research is relevant. The scientific novelty of the work is due to the lack of a comprehensive study of patho-anatomical metaphorical binary terms that would explain the emergence of metaphorical meaning in the Ukrainian language. Research methods. At the analytical stage, the method of purposeful sampling was used to select metaphorical binary terms and create their index. At the stage of analysis of the translation, as well as at other stages, the comparative method was applied, which served as the basis for an adequate translation. Conclusions. The translation of such terminological compounds as wolf's mouth, cobbler's chest, horse's foot, cherry eye, hare's eye, etc. has been studied. The theoretical foundations of the study of terminological metaphor in modern linguistics have been specified, as a result of which classification features of metaphorical binaries included in the layer of pathoanatomical terminology have been singled out. It is noted that a typical variant for the emergence of a metaphor is external similarity and acoustic similarity (cat cry syndrome)

Abstract P3192: Prdm16 Regulates Cardiac Metabolic Genes Through Perm1

The heart is a metabolically demanding organ that requires significant amounts of energy to function properly, and even minor metabolic deficiencies during development can lead to heart failure. Cardiomyopathies are a group of conditions that affect the heart's contractile function, and PRDM16 deficiency is a primary cause of cardiomyopathies associated with 1p36 deletion syndrome in humans. Conditional deletion of Prmd16 in the heart causes a spectrum of cardiac phenotypes including left ventricular non-compaction, late-onset heart failure, and dilated cardiomyopathy. Still, the mechanisms underlying these cardiac phenotypes with loss of Prdm16 are not fully understood. We and others demonstrated that lack of Prdm16 in the heart causes alterations in fatty acid (FA) oxidation and oxidative phosphorylation (OXPHOS) gene expression. Further, we now show that Prdm16 cardiac deletion reduces the expression of key regulators of FA oxidation and OXPHOS genes including Perm1. Loss and gain of Prdm16 function in vitro confirmed a cell-autonomous regulation of Perm1 by Prdm16 in H9c2 rat cardiomyoblasts and neonatal rat ventricular myocytes (NRVMs). Prdm16 ChIP-sequencing analysis of embryonic hearts revealed direct binding of Prdm16 to the promoter of Perm1. Prdm16 binding to Perm1 promoter was further confirmed by ChIP-qPCR in H9c2 cells. Knockdown of Prdm16 in NRVMs reduced maximal mitochondrial respiration, which was rescued by over-expressing Perm1. Further, PERM1 mRNA was diminished in human induced pluripotent stem cells-derived cardiomyocytes (iPSC-CMs) derived from a patient with a PRDM16 mutation (Q187X). These results are evidence that PRDM16 is an upstream regulator of PERM1 in the heart.

Evaluation of noninvasive prenatal screening for copy number variations among screening laboratories

ObjectiveTo evaluate the current situation of expanded noninvasive prenatal screening (NIPS) for copy number variations (CNVs) in laboratories in China, the National Center of Clinical Laboratories conducted an externalqualityassessment (EQA) program. MethodsThe EQA panel consisted of 12 artificial samples associated with different syndromes, which were mixed with maternal plasma collected from pregnant women and enzyme-digested cell-free DNA (cfDNA) from cell lines with different fetal fractions (FFs) ranging from 5% to 15%. The panel was validated by next-generation sequencing and distributed to laboratories, along with questionnaires and case scenarios. ResultsSixty-nine laboratories participated in the EQA program, and 91.30% (63/69) of laboratories correctly identified all samples. A total of 7.25% (5/69) of the laboratories reported false-negative results, and 2.90% (2/69) of the laboratories reported unexpected CNVs. The correct rates of the 22q11.2 deletion syndrome, Cri-du-chat syndrome, 1p36 deletion syndrome and Angelman/Prader-Willi syndrome samples were 97.46%, 98.55%, 100%, and 100%, respectively. With the increase in the FF, deletion size, and read depth, the detection rate increased. For results reports, only five laboratories reported FF values, one laboratory reported the CNV classification type, and none reported sensitivity, specificity, positive predictive values, and negative predictive values. ConclusionThe detection capabilities of NIPS for CNVs still need to be improved and standardized, and FF, deletion size, and read depth are factors that affect the detection rate.

Identification of an 85-kb Heterozygous 4p Microdeletion With Full Genome Analysis in Autosomal Dominant Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMT) is a syndrome of a hereditary neurodegenerative condition affecting the peripheral nervous system and is a single gene disorder. Deep phenotyping coupled with advanced genetic techniques is critical in discovering new genetic defects of rare genetic disorders such as CMT. We applied multidisciplinary investigations to examine the neurophysiology and nerve pathology in a family that fulfilled the diagnosis of CMT2. When phenotype-guided first-tier genetic tests and whole-exome sequencing did not yield a molecular diagnosis, we conducted full genome analysis by examining phased whole-genome sequencing and whole-genome optical mapping data to search for the causal variation. We then performed a systematic review to compare the reported patients with interstitial microdeletion in the short arm of chromosome 4. In this family with CMT2, we reported the discovery of a heterozygous 85-kb microdeletion in the short arm of chromosome 4 (4p16.3)[NC_000004.12:g.1733926_1819031del] spanning 3 genes [TACC3 (intron 6-exon 16), FGFR3 (total deletion), and LETM1 (intron 10-exon14)] that cosegregated with disease phenotypes in family members. The clinical features of peripheral nerve degeneration in our family are distinct from the well-known 4p microdeletion syndrome of Wolf-Hirschhorn syndrome, in which brain involvement is the major phenotype. In summary, we used the full genome analysis approach to discover a new microdeletion in a family with CMT2. The deleted segment contains 3 genes (TACC3, FGFR3, and LETM1) that likely play a role in the pathogenesis of nerve degeneration.

Efficacy of antiseizure medications in Wolf-Hirschhorn syndrome.

Wolf-Hirschhorn syndrome (WHS) is caused by deletion of the terminal region of chromosome 4 short arm and is frequently associated with intractable epilepsy. To evaluate the clinical features of epileptic seizures in WHS and the therapeutic efficacy of oral antiseizure medications (ASMs) Methods: Patients with WHS who were treated for epilepsy at the Saitama Children's Medical Center under 5 years of age were included. WHS was diagnosed based on genetic tests and clinical symptoms. Medical records regarding the age of onset of epilepsy, seizure type, treatment of status epilepticus (SE), and effectiveness of ASMs were retrospectively reviewed. Oral ASMs were considered effective when seizures were reduced by at least 50% compared to the pre-medication level. Eleven patients were included in the study. The median age at the onset of epilepsy was 9 months (range: 5-32 months). Unknown-onset bilateral tonic-clonic seizure was the most common type of seizure, occurring in ten patients. Focal clonic seizures occurred in four patients. Ten patients exhibited recurrent episodes of SE, and its frequency during infancy was monthly in eight patients and yearly in two. SE occurrence peaked at 1 year of age and decreased after 3 years of age. The most effective ASM was levetiracetam. Although WHS-associated epilepsy is intractable with frequent SE occurrence during infancy, improvement in seizure control is expected with age. Levetiracetam may be a novel ASM for WHS.

Ayurvedic Approach Towards Wolf-Hirschhorn Syndrome: A Case Report

Wolf-Hirschhorn Syndrome is a rare chromosomal disorder caused by the partial deletion (structural aberration) of the short arm of chromosome 4. It is also known as 4P syndrome. The disease was first reported by Cooper, Hirschhorn and Wolf. The characteristic features of the patient depend on the extent of deletion of the genetic materials. The patient has craniofacial dysmorphism and the dysmorphic features are collectively known as Greek Warrior Helmet Facies. There is no direct correlation available for Wolf-Hirschhorn Syndrome in Ayurveda. Since it is a congenital pathology occurring due to chromosomal aberration it may be understood as a Sahaja vyadhi caused due to Beeja dosha. Here in this case the micro/partial deletion of genetic materials from short arm of chromosome 4 is due to the Beeja dosha that has occurred during the formation of Garbha (zygote). This Beeja dosha is responsible for the manifestation of different presentation in Wolf-Hirschhorn Syndrome which can be understood as a Vyadhi Sankara i.e., syndrome. The patient was presented with the features of facial dysmorphism, hypospadias, developmental delay and seizures. Hence the case was diagnosed as Vyadhija Phakka with Vataja Apasmara. In the present case the focus was mainly in the correction of developmental delay and to prevent the relapse of seizures. An integrated treatment protocol comprising Phakka chikitsa and Vataja Apasmara chikitsa were administered. Though there was no change in the facial dysmorphisms, but significant improvements were observed in the gross motor, language and communication milestones after the treatment.

WHSC1 is involved in DNA damage, cellular senescence and immune response in hepatocellular carcinoma progression

Wolf-Hirschhorn syndrome candidate 1 (WHSC1) is a transcriptional regulatory protein that encodes a histone methyltransferase to control H3K36me2 modification. WHSC1 was upregulated and associated with poor prognosis in HCC. The elevated WHSC1 likely due to the alterations of DNA methylation or RNA modification. WHSC1 perhaps form a chromatin cross talk with H3K27me3 and DNA methylation to regulate transcription factors expression in HCC. Functional analysis indicated that WHSC1 was involved in DNA damage repair, cell cycle, cellular senescence and immune regulations. Furthermore, WHSC1 was associated with the infiltrating levels of B cell, CD4+, Tregs and macrophage cells. Therefore, our findings suggested that WHSC1 might function as a promotor regulator to affect the development and progression of HCC. Thus, WHSC1 could be a potential biomarker in predicting the prognosis and therapeutic target for patients with HCC.

NSD3, a member of nuclear receptor-binding SET domain family, is a potential prognostic biomarker for pancreatic cancer.

Members of the nuclear receptor-binding SET domain (NSD) family of histone H3 lysine 36 methyltransferases comprise NSD1, NSD2 (MMSET/WHSC1), and NSD3 (Wolf-Hirschhorn syndrome candidate 1-like 1, WHSC1L1). While the expression of NSD genes is essential to normal biological processes and cancer, knowledge of their expression levels to prognosticate in cancer remains unclear. We analyzed the expression patterns for NSD family genes across multiple cancer types and examined their association with clinical features and patient survival profiles. Next, we explored the association between NSD3 expression and described features of the tumor microenvironment (TME) in PAAD, a severe type of pancreatic cancer. In particular, we correlated promoter methylation levels for NSD3 with patient outcomes in PAAD. Finally, we explored the putative oncogenic roles for NSD3 using a series of experiments with pancreatic cancer cells. We report that the expression of NSD family members is correlated with clinical prognosis across multiple types of cancers. Also, we demonstrate that NSD3 variants are most prevalent among NSD genes across cancers we analyzed. Notably, when compared with NSD1 and NSD2, we find that NSD3 is prominently expressed, and its expression is significantly linked with clinical outcome in pancreatic cancer. Furthermore, NSD3 is frequently amplified, exhibits low promoter methylation, and is correlated with immune cell infiltration and enhanced proliferation of pancreatic cancer. Finally, we demonstrate that knockdown of NSD3 alters H3K36me2 methylation, downstream gene expression and EGFR/ERK signaling in pancreatic cancer cells. We find that expression levels, the presence of genetic variants of NSD family genes, as well as their promoter methylation are correlated with clinical outcomes in cancer, including pancreatic cancer. Our in vitro experiments suggest that NSD3 may be relevant to gene expression regulation and growth factor signaling in pancreatic cancer.

Estimation on risk of spontaneous abortions by genomic disorders from a meta-analysis of microarray results on large case series of pregnancy losses.

A meta-analysis on seven large case series (>1000 cases) of chromosome microarray analysis (CMA) on products of conceptions (POC) evaluated the diagnostic yields of genomic disorders and syndromic pathogenic copy number variants (pCNVs) from a collection of 35,130 POC cases. CMA detected chromosomal abnormalities and pCNVs in approximately 50% and 2.5% of cases, respectively. The genomic disorders and syndromic pCNVs accounted for 31% of the detected pCNVs, and their incidences in POC ranged from 1/750 to 1/12,000. The newborn incidences of these genomic disorders and syndromic pCNVs were estimated in a range of 1/4000 to 1/50,000 live births from population genetic studies and diagnostic yields of a large case series of 32,587 pediatric patients. The risk of spontaneous abortion (SAB) for DiGeorge syndrome (DGS), Wolf-Hirschhorn syndrome (WHS), and William-Beuren syndrome (WBS) was 42%, 33%, and 21%, respectively. The estimated overall risk of SAB for major genomic disorders and syndromic pCNVs was approximately 38%, which was significantly lower than the 94% overall risk of SAB for chromosomal abnormalities. Further classification on levels of risk of SAB to high (>75%), intermediate (51%-75%), and low (26%-50%) for known chromosomal abnormalities, genomic disorders, and syndromic pCNVs could provide evidence-based interpretation in prenatal diagnosis and genetic counseling.

18p Deletion Syndrome With Concurrent Frizzled-4 Mutation: Surgical Management of Bilateral Stage 5 Traction Retinal Detachment.

We report a case of a patient with 18p deletion syndrome and concurrent FZD4 (frizzled-4) mutation. A 6-month-old boy with known 18p deletion syndrome presented with abnormal eye movements in both eyes and an inability to track objects. The patient had a history of laryngomalacia, hypotonia, and developmental delay. Examination showed bilateral total exudative and traction retinal detachment with anomalous retinal vascular development noted on widefield fluorescein angiography. Genetic analysis identified a concurrent FZD4 mutation (c.205C>T [p.H69Y]). Both eyes underwent 25-gauge limbal vitrectomy, lensectomy, and membrane peeling, and the posterior pole successfully reattached with improvement in visual function. The 18p region contains the LAMA1, TGIF1, and APCDD1 genes, which are involved in the vascular basement membrane and Wnt/β-catenin signaling, which may have potentiated the particularly severe familial exudative vitreoretinopathy phenotype. We present the clinical findings, imaging analyses, and surgical management of concurrent 18p deletion syndrome and FDZ4 mutation. The overlap in molecular mechanisms of the multiple gene products may potentiate the severe phenotype. [Ophthalmic Surg Lasers Imaging Retina 2023;54:284-290.].

Hirschsprung's disease in a genetically diagnosed Cri-du-chat syndrome baby

Hirschsprung's disease (HSD) is a congenital disease characterized by the absence of ganglion cells in the myenteric and submucosal plexuses of the gastrointestinal tract. Many genetic causes of HSD have been investigated, although the most common and widely accepted is the RET gene located on chromosome 10q11.2. The presence of other coinciding genetic abnormalities with HSD, such as Cri-du-chat (CDC) syndrome, might provide a better understanding of the genetic bases of the disease. We present a case of a term baby boy who had features of Cri-du-chat syndrome at birth that were confirmed genetically. Later, the patient developed features of lower GI obstruction and was diagnosed with HSD by suction rectal biopsy. He underwent surgery and recovered well. We conclude that physicians involved in the care of babies with CDC and lower GI obstruction should consider the possibility of HSD and investigate accordingly. Additionally, when CDC and HSD coexist in a patient, the CDC genotype should be determined by whole exome sequencing and examined to identify mutations associated with HSD.

Phenotypic and cytogenetic features of an Iranian child with tetrasomy 18p syndrome: A case report

Phenotypic and cytogenetic features of an Iranian child with tetrasomy 18p syndrome: A case report

Familial 4p Interstitial Deletion Provides New Insights and Candidate Genes Underlying This Rare Condition

Chromosome 4p deletions can lead to two distinct phenotypic outcomes: Wolf--Hirschhorn syndrome (a terminal deletion at 4p16.3) and less frequently reported proximal interstitial deletions (4p11-p16). Proximal 4p interstitial deletions can result in mild to moderate intellectual disability, facial dysmorphisms, and a tall thin body habitus. To date, only 35 cases of proximal 4p interstitial deletions have been reported, and only two of these cases have been familial. The critical region for this syndrome has been narrowed down to 4p15.33-15.2, but the underlying causative genes remain unclear. In this study, we report the case of a 3-year-old female with failure to thrive, developmental and motor delays, and morphological features. The mother also had a 4p15.2-p14 deletion, and the proband was found to have a 13.4-Mb 4p15.2-p14 deletion by chromosome microarray analysis. The deleted region encompasses 16 genes, five of which have a high likelihood of contributing to the phenotype: PPARGC1A, DHX15, RBPJ, STIM2, and PCDH7. These findings suggest that multiple genes are involved in this rare proximal 4p interstitial deletion syndrome. This case highlights the need for healthcare providers to be aware of proximal 4p interstitial deletions and the potential phenotypic manifestations.

The leucine zipper EF-hand containing transmembrane protein-1 EF-handis an atypical tripartite calcium, temperature, and pH sensor.

Mitochondrial calcium (mtCa2+) is integral to ATP production; however, excessive Ca2+ leads to cell death. Both these processes are crucial to cellular function, and thus mtCa2+ homeostasis is tightly regulated. Leucine zipper EF-hand containing transmembrane protein-1 (LETM1) is an essential inner-mitochondrial membrane protein that regulates mtCa2+ through exchange of Ca2+ for protons (H+). LETM1 haploinsufficiency is associated with Wolf-Hirschhorn syndrome, characterized by microcephaly, growth retardation, and epileptic seizures, indicating a fundamental function for LETM1 in humans. LETM1 contains a conserved Ca2+ binding EF-hand motif (EF1). Deletion of EF1 abrogates LETM1 mediated mtCa2+ flux, but the precise mechanism by which EF1 regulates exchanger function remains unknown. To begin understanding the role of EF1 in LETM1 function, we biophysical and structurally characterized isolated EF1. Our data show that EF1 exhibits augmented α-helical secondary structure, solvent exposed hydrophobicity and oligomerization in the presence of Ca2+ due to a weak but specific, Ca2+-binding affinity. The low affinity is, in part, due to a terminal Asp within the binding loop, where mutation to Glu increases the affinity ∼4-fold. EF1 is structurally sensitive to pH changes within the physiological range for mitochondria, and remarkably, unfolds at high and low temperatures. Using solution NMR spectroscopy, we reveal that EF1 adopts an atypical EF-hand arrangement by pairing with an upstream loop-helix motif. Collectively, our data suggest that EF1 functions as a divergent multipartite environmental sensor within the EF-hand protein family by adopting an inimitable three-helix EF-hand domain arrangement in LETM1.

Wolf-Hirschhorn syndrome revealed by status epilepticus: A case report

A Wolf-Hirschhorn syndrome is a rare chromosomal anomaly, which results from a deletion of the distal portion of the short arm of chromosome 4 (4p-), the diagnosis is based on a clinical picture, easily recognizable in children, confirmed by molecular cytogenetics. We report the case of baby with wolf-Hirschhorn syndrome revealed by status epilepticus.

Wolf-Hirschhorn syndrome revealed by status epilepticus: A case report

Wolf-Hirschhorn syndrome revealed by status epilepticus: A case report

Profiles of autism characteristics in thirteen genetic syndromes: a machine learning approach

BackgroundPhenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes.MethodsProfiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader–Willi n = 278, Lowe n = 89, Smith–Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein–Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan–McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor.ResultsGenetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader–Willi, Rubinstein–Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith–Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy.LimitationsThe key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups.ConclusionsThese findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.

Prenatal diagnosis for a fetus with 5p deletion syndrome

To explore the genetic basis for a fetus with club foot detected upon mid-pregnancy ultrasonography. Amniotic fluid of the fetus and peripheral blood samples of its parents were collected and subjected to G-banding karyotype analysis and copy number variation sequencing (CNV-seq). The result was verified by fluorescence in situ hybridization (FISH). The fetus and its parents all had a normal karyotype. CNV-seq analysis revealed that the fetus has harbored a 23.12 Mb on chromosome 5 and a 21.46 Mb duplication on chromosome 7. FISH assay has verified that its mother has carried a cryptic t(5;7)(p14.3;q33) translocation. CNV-seq combined with FISH can effectively detect cryptic chromosome aberrations, and can help to reduce severe birth defects and provide a basis for prenatal genetic counseling.

Síndrome de Cri Du Chat (síndrome do miado de gato) e a inclusão escolar

This study offers reflections on the inclusion of children with Cri Du Chat Syndrome (CCS), a rare condition of genetic origin. OBJECTIVES: To discuss the inclusion of children with CCS in schools and describe the characteristics, diagnosis, treatment, and main symptoms of the condition, along with the main difficulties students with CCS might face; to assess the knowledge teachers have about CCS and potential teaching resources they may use. METHOD: A digital survey questionnaire was used in this qualitative exploratory descriptive study. RESULTS: Only 14.8% of the 27 teachers who responded the questionnaire had knowledge about CCS and had worked in a classroom with adapted pedagogical practices. CONCLUSION: A very small portion of teachers had knowledge about CCS and most had never been in contact with individuals with the syndrome, either in a classroom or during training. A path has to be developed for the inclusion of children with CCS, through a process based on knowledge, affection, love, and respect for differences.

Anaesthetic Considerations for General Anaesthesia in an Adult Patient with Wolf-Hirschhorn Syndrome and Kyphoscoliosis: A Case Report

Wolf-Hirschhorn Syndrome (WHS), also known as Chromosome 4 deletion syndrome, is a rare hereditary disease with a prevalence of 1 in 50,000. It occurs due to the microdeletion of the short arm of chromosome 4, specifically the 4p16.3 domain. Patients with WHS exhibit diverse phenotypes, including growth retardation, developmental delay, congenital heart disease, and convulsions, depending on the amount of deleted genetic material. This case report focuses on a 25-year-old male who was admitted for cataract extraction and posterior chamber intraocular lens implantation. Through gene analysis, the patient was diagnosed with WHS. He exhibited micrognathia, a short neck, kyphoscoliosis, seizure disorder, and mental retardation. Additionally, he had severe kyphoscoliosis, which resulted in restrictive lung disease. These abnormalities posed significant challenges for anaesthetic management. To ensure a successful general anaesthesia, adequate preparedness for difficult airway management was crucial. A thorough cardiovascular and neuromuscular examination was conducted preoperatively to rule out associated anomalies and minimise complications. The patient’s perioperative antiepileptic cover was continued. Extubation proved challenging due to the patient’s mental retardation and restrictive lung disease. This case underscores the importance of effective anaesthetic management for patients with this rare condition undergoing cataract surgery under general anaesthesia.