Deep-set Eyes Research Articles

Features of Ugly but Capable Women of Ancient China.

The aim of this study was to analyze the appearance of women viewed as "ugly but capable" in ancient China. A Google search was conducted for the "Four Great Ugly Women." Information on 3 women was collected from Lienüzhuana, a collection of biographies of eminent women compiled by the Former Han period. With the addition of 1 (Huang Yueying), 7 "ugly but capable" women were analyzed. The manifestations of their ugliness in the texts were recorded. Among the 7 women, 5 exhibited physical manifestations, whereas the remaining 2 were simply described as "ugly" without specific characteristics. Among the discernible body characteristics of the 5 women deemed unattractive, the most common feature was dark skin (80%), followed by body shape (60%). Other frequently observed traits included sparse or yellow hair, an upturned or overly large nose, a convex forehead, and an unattractive neck (each at 40%), with the latter potentially exhibiting a protruding Adam's apple, a thick neck, or a neck mass. Less common features were sunken eyes, a large head, and a masculine skeleton, each occurring in 20% of cases. Based on the depiction of women considered unattractive, the authors can infer that dark skin, a fat body, a large or upturned nose, sparse hair, a protruding forehead, a thick neck, deep-set eyes, and a large head were elements associated with ugliness. Through the description of the ugly woman, authors can infer the standards of ugliness in ancient China.

A Rare Consanguineous Case of Alazami Syndrome in a Jordanian Family: Clinical Presentation, Genetic Analysis, and Therapeutic Approaches - A Case Report

Objective: Alazami syndrome (AS) is an infrequent genetic disorder inherited in an autosomal recessive pattern, characterized by the presence of multiple congenital abnormalities. This study explores a case of a 4-year-old girl with AS, examining symptoms, genetic factors, and treatment efficacy. Case report: A 4-year-old girl, born to consanguineous Jordanian parents, displayed dysmorphic features including low birth weight, microcephaly, hyperthyroidism, short stature, blue sclera, triangular-shaped face, deep-set eyes, narrow palpebral fissures, and a prominent forehead. Examination revealed height (92 cm) and weight (7.7 kg) below the 5th and 3rd percentiles respectively. Blood tests and renal ultrasound were normal. Whole exome sequencing (WES) identified a homozygous eight-base pair deletion within exon 5 of the LARP7 gene on chromosome 4q25, confirming the diagnosis of AS, an autosomal recessive disorder. This variant induces frameshift mutations leading to premature stop codons, suggesting a probable mechanism of illness via loss of function. Treatment involving growth monitoring and therapy led to significant improvements in height, weight, and communication skills within three months. Conclusion: We describe a rare autosomal recessive AS case due to consanguinity, with a frameshift mutation in the LARP7 gene found via WES. Our AS treatment program effectively alleviates symptoms and enhances developmental progress.

NKX2-1-conditioned disorder — «brain–lung–thyroid» syndrome: results of a multicenter study

Introduction. Brain–lung–thyroid syndrome (BLTS, choreoathetosis and congenital hypothyroidism with or without pulmonary dysfunction) is an autosomal dominant disorder associated with mutations of the NKX2-1 gene. A triad of symptoms from three organs (brain, lungs, thyroid gland) is manifested in 50% of patients, in other cases there is an incomplete phenotype of the disease. The most common manifestations are neurological. The aim of the study was to provide genetic, clinical, laboratory, and instrumental characteristics in BLTS patients with a clinical and morphological assessment of the phenotype.
 Materials and methods. Ten children from 9 families with identified mutations in the NKX2-1 gene were observed. Methods used: genealogical, Sanger sequencing, clinical and morphological assessment of the phenotype, examination of thyroid hormone levels, CT, MRI of the brain, CT of the chest, lung biopsy.
 Results. The article presents the results of molecular genetic analysis, family history, age of manifestation and diagnosis. 9 out of 10 children had damage to the central nervous system, thyroid gland, lungs, and one child had a combination of neurological pathology and hypothyroidism. Neurological pathology was represented by benign hereditary chorea (2 children), delayed motor development (8), muscular hypotension (7), ataxia (5), choreoathetosis (1), clonuses (1), seizures (1), hyperkinesis (3); respiratory — respiratory distress syndrome (RDS) of newborns (6), chronic respiratory failure (5), interstitial lung disease (6), bronchial asthma (1), chronic pneumonitis of infants (1), bronchiectasis (1). There are presented changes in computed tomograms of the lungs and during preforming CT, MRI of the brain. Typical developmental microanomalia included a protruding forehead, a wide tip of the nose, elongated narrow palpebral fissure, deep-set eyes, hypertelorism of the eyes, large rotated low-lying auricles, conical fingers.
 Conclusion. A combination of congenital hypothyroidism, neonatal RDS, heart disease, neurological disorders (hypotension, ataxia, delayed motor development, chorea), craniofacial dysmorphia is the basis for a molecular genetic examination to exclude BLTS.

Lamb-Shaffer syndrome: 20 Spanish patients and literature review expands the view of neurodevelopmental disorders caused by SOX5 haploinsufficiency.

Lamb-Shaffer Syndrome (LSS; OMIM #616803; ORPHA #313892; ORPHA #313884) is an infrequent genetic disorder that affects multiple aspects of human development especially those related to the development of the nervous system. LSS is caused by variants in the SOX5 gene. At the molecular level, SOX5 gene encodes for a transcription factor containing a High Mobility Group (HMG) DNA-Binding domain with relevant functions in brain development in different vertebrate species. Clinical features of Lamb-Shaffer syndrome may include intellectual disability, delayed speech and language development, attention deficits, hyperactivity, autism spectrum disorder, visual problems and seizures. Additionally, patients with the syndrome may present distinct facial dimorphism such as a wide mouth with full lips, small chin, broad nasal bridge, and deep-set eyes. Other physical features that have been reported in some patients include short stature, scoliosis, and joint hypermobility. Here, we report the clinical and molecular characterization of a Spanish LSS cohort of new 20 patients and review all the patients published so far which amount for 111 patients. The most frequent features included developmental delay, intellectual disability, visual problems, poor speech development and facial dysmorphic features. Strikingly, pain insensitivity and hypermetropia seems to be more frequent than previously reported, based on the frequency seen in the Spanish cohort. Eighty-three variants have been reported so far, single nucleotide variants (SNV) and copy number variants represent 47% and 53%, respectively, from the total of variants reported. Similarly to previous reports, the majority of the SNVs variants of the novel patients reported herein fall in the HMG domain of the protein. However, new variants, affecting other functional domains, were also detected. In conclusion, LLS is a rare genetic disorder mostly characterized by a wide range of developmental and neurological symptoms. Early diagnosis would allow to start of care programs, clinical follow up, prospective studies and appropriate genetic counseling, to promote clinical and social improvement to have profound lifelong benefits for patients and their families. Further research is needed to better understand the underlying mechanisms of the syndrome related to SOX5 haploinsufficiency.

Chinese visions of self and Other: the international politics of noses

Abstract How does China view the world? While much has been written about how China's international relations are best seen as intercultural relations that do not exclude the Other, this article examines how self/Other relations are visualized in terms of the human face in China, in particular through iconic images that construct the Chinese self with and against foreigners with large noses. It employs interpretivist methods to consider the interplay of social relations and international relations in order to see how ‘external appearance’ and ‘external relations’ inform each other in Chinese theory and practice. It mobilizes the classical Chinese concept ‘deep-set eyes and high-bridged nose’ to compare iconic Chinese images of noses from the Tang dynasty, the Korean War, and twenty-first century China and Taiwan. This critical juxtaposition shows how foreigners are visualized as both friends and enemies in a hierarchical social system. The article's use of visual International Relations (IR) methods enables us to re-examine foreign affairs as a site of affective politics, and thus appreciate how China's ideological world-view resonates with how its artists, scholars and officials aesthetically view the world. This is a concern for IR scholars because world-views shape how foreign policy-makers frame foreign policy problems—and thus foreign policy solutions.

Novel Pathogenic Variant in PIEZO2 in a Korean Patient with Distal Arthrogryposis

Alterations in <i>PIEZO2</i> can result in distal arthrogryposis, which is characterized by non-progressive contracture in two or more areas of the body prior to birth. Here, we present a 29-year-old man born with multiple joint contractures and cleft palate. He showed short stature, low-set ears, macrotia, hearing impairment, micrognathia, a triangular face, blepharophimosis, deep-set eyes, high arched eyebrows, decreased facial expressions, retrognathia, arachnodactyly, absent phalangeal crease, shortening of the first and fifth toes, short stature, pectus excavatum, epicanthus, bilateral ptosis, and ophthalmoplegia. He also complained of dyspnea and severe kyphoscoliosis. Pulmonary function tests showed a severe restrictive pattern. An electrodiagnostic study did not reveal any neurogenic or myogenic features. Next-generation sequencing revealed a novel de novo heterozygous pathogenic variant in <i>PIEZO2</i> (c.7251G>T; p.Trp2417Cys). Our study is the first report of a pathogenic variant in <i>PIEZO2</i> in a Korean patient with distal arthrogryposis.

Hyper‐IgE syndrome presenting with early life craniosynostosis in monozygotic twin sisters

<scp>Hyper‐IgE</scp> syndrome presenting with early life craniosynostosis in monozygotic twin sisters

The neurodevelopmental and facial phenotype in individuals with a TRIP12 variant.

Haploinsufficiency of TRIP12 causes a neurodevelopmental disorder characterized by intellectual disability associated with epilepsy, autism spectrum disorder and dysmorphic features, also named Clark-Baraitser syndrome. Only a limited number of cases have been reported to date. We aimed to further delineate the TRIP12-associated phenotype and objectify characteristic facial traits through GestaltMatcher image analysis based on deep-learning algorithms in order to establish a TRIP12 gestalt. 38 individuals between 3 and 66 years (F = 20, M = 18) - 1 previously published and 37 novel individuals - were recruited through an ERN ITHACA call for collaboration. 35 TRIP12 variants were identified, including frameshift (n = 15) and nonsense (n = 6) variants, as well as missense (n = 5) and splice (n = 3) variants, intragenic deletions (n = 4) and two multigene deletions disrupting TRIP12. Though variable in severity, global developmental delay was noted in all individuals, with language deficit most pronounced. About half showed autistic features and susceptibility to obesity seemed inherent to this disorder. A more severe expression was noted in individuals with a missense variant. Facial analysis showed a clear gestalt including deep-set eyes with narrow palpebral fissures and fullness of the upper eyelids, downturned corners of the mouth and large, often low-set ears with prominent earlobes. We report the largest cohort to date of individuals with TRIP12 variants, further delineating the associated phenotype and introducing a facial gestalt. These findings will improve future counseling and patient guidance.

Interstitial Duplication on Chromosome 3p14.3p13 in an Adolescent with Dysmorphic Features and Autism, Case Report

Abstract Introduction/Objective The genetic etiology of autism spectrum disorders is only partially understood. Here we describe a 16-year-old male diagnosed with autism at two years of age. He has dysmorphic features, severe cognitive disability, and history of cryptorchidism. A review of systems was significant for slightly coarse features overall, with deep-set eyes, pinched nasal bridge with wide nasal tip, and widely spaced teeth. A large pectus excavatum deformity was also noted. Although the parent’s genetic testing concluded that this likely represents de novo mutation, it is worth mentioning that our patient has a 13-year-old female maternal first cousin with learning difficulties that were said to be less severe. There is no other family history of autism. Methods/Case Report Chromosome analysis showed an abnormal karyotype identifying a duplication of the short arm of chromosome 3 from p13 to p14.3, 46,XY,dup(3)(p13p14.3). Additional microarray testing confirmed this duplication and defined the size as 14.9 Mb. Regions of homozygosity of 29.8 Mb were also identified, representing about 1% of the autosomal genome. The duplicated area includes over 70 genes, thirteen of which are known Mendelian disease genes (IL17RD, HESX1, APPL1, FLNB, DNASEIL3, PDHB, ACOX2, ATXN7, SLC25A26, EOGT, LMOD3, MITF, and FOXP1). Duplications of 3p are extremely rare and can be de novo or inherited from a parent with a balanced translocation. Individuals with these better-described chromosome 3p duplications typically present with intellectual and developmental disabilities, such as autism, as 3p duplications typically present with intellectual and developmental disabilities, such as autism and distinctive dysmorphic features. This duplication has never been reported as a known syndrome and has minimal overlap with copy number variants (CNVs) among healthy individuals. Results (if a Case Study enter NA) NA Conclusion Autism spectrum disorders are largely characterized by speech, communication, and social impairment of varying degrees. Diagnosis is typically made on clinical grounds, but in 14-35% of cases, a genetic basis for the disorder, typically either due to a single gene disorder or a chromosomal deletion/duplication, may be found. This case report describes a rare finding of a 14.9 Mb interstitial duplication on chromosome 3p.

Cover Art Concept

The patterns that adorn the carpets carry within them people’s memory. In Kurdish lands also, carpets are an important means of expression.The women get together and, while singing, tell their stories on their looms, thread after thread, with their fingertips. . . . Mardin, a city in southeastern Turkey, stands on part of the Kurdish lands, which were divided like a pie in four, a hundred years ago, between Iraq, Iran, Syria, and Turkey. I was born there.Stories lurk on each of the historical streets that crisscross Mardin and turn it into a labyrinth—my town with the ocher atmosphere. Armenians, Arabs, Syriacs, Chaldeans, Mahallamis, Kurds: in this town we have all lived together for centuries. At times the history of the powerful led us to kill one another: the Syriac genocide in 1914–20, the Armenian genocide that began in 1915, then the policies of genocide and assimilation targeting the Kurdish people. . . . By itself, Mardin is like a prototype of Kurdistan: centuries-old peoples, each with their own painful history, holding on to a profound dignity without ever giving it up.In this town, at every turn, you come across women with black, deep-set eyes that say everything. Women who go on living without forgetting their bitter history, who move on, not with sickly hatred in their hearts but with the determination to surmount everything by deeply inhaling the air of the alleyways.

Is facial structure an honest cue to real-world dominance and fighting ability in men? A pre-registered direct replication of

Masculine facial morphology (e.g., larger jaw, prominent cheekbones) have been linked to a suite of social outcomes—including greater wealth, career progress, romantic desirability, and even greater political success. A leading explanation for these links is that dominant facial structures represent honest cues of physical dominance and fighting ability. Třebický et al. (2013) published the first study to demonstrate that masculine facial cues (e.g., large nose, deep-set eyes) similarly predict both dominance judgments and real-world fighting success, but no studies have replicated these popular findings that a large and specific assortment of masculine facial structures are implicated in both fighting ability and dominance perception. Thus, we conducted a pre-registered direct replication and extension of Třebický et al. (2013). Two separate samples of United States MTurk participants rated 516 UFC fighters' facial photographs on perceived aggressiveness (N = 500) and fighting ability (N = 500). Results showed that perceived aggressiveness was associated with masculine facial morphology (e.g., large nose, deep-set eyes) independent of bodily size. There was also some evidence that perceived fighting ability was associated with masculine facial morphology, which disappeared after controlling for bodily size. There was no support for the relation between facial structure and fighting success, and there were often negative relations between perceived aggressiveness and fighting ability on fighting success (i.e., more successful fighters were perceived as less successful and aggressive). We argue that our evolved psychology differentially processes the distinct avenues to victory that constitute overall fighting success (e.g., knockout versus submission wins).

Clinical characteristics and genetic analysis of a neonate with Smith-Magenis syndrome

To explore the clinical features and genetic etiology for a neonate with Smith-Magenis syndrome (SMS). Copy number variation sequencing (CNV-seq) was applied to the neonate and his parents, and the genotype-phenotype correlation was analyzed. On the second day after birth, the neonate had presented with pathological jaundice and immunodeficiency. Cranial MRI revealed ventricular enlargement and enlargement of cisterna magna. At 3 months, the infant has presented with square face, prominent forehead, deep-set eyes, hypertelorism, palpebral fissure upward and button noses. Genetic testing showed that he had carried a 2.9 Mb deletion in 17p11.2 region, seq[GRCh37] del(17)(p11.2)(chr17:16 836 379-19 880 992). The same deletion was not found in either parent. SMS is mostly diagnosed in child and adulthood, but rarely in neonates. For neonates with SMS, the neurological and behavioral abnormalities have not been shown, but pathological jaundice, CNS abnormalities and immune deficiency may be the characteristics, which require attention of neonatal physicians.

Oral Facial Manifestations of Sanjad-Sakati Syndrome: A Literature Review.

Aim: To perform a comprehensive review of orofacial manifestations of Sanjad–Sakati syndrome (SSS). Methods: A comprehensive electronic literature search was performed using PubMed, Scopus and Cochrane library databases. The search keywords included were “Sanjad–Sakati syndrome (SSS)”, “dental manifestations”, “dental management”, “oral health”, “dental care for patients with SSS”, “dental health of people with SSS”, “caries”, and “oral hygiene”. The inclusion criteria were papers published only in English, papers published by August 2021, and papers discussing orofacial manifestations of SSS and language. Results: The search of the databases retrieved eleven case reports and three case series studies. Overall, 56 cases (11 case reports and 3 case series studies) were reported on Sanjad–Sakati syndrome in the published literature. The majority of the reports are from the Middle Eastern region. Conclusions: The reported orofacial manifestations of SSS include beaked nose, depressed nasal bridge, enamel hypoplasia, hypodontia, low-set ears, posteriorly rotated ears, deep-set eyes, microcephaly, microdontia, micrognathia, prominent forehead, retrognathia, and thin lips. The review paper also establishes the importance of the dental under general anesthesia in SSS individuals.

EP455: Fetal ultrasound presentation and neonatal diagnosis of Freeman-Sheldon syndrome in son of previously undiagnosed adult male

eP455: Fetal ultrasound presentation and neonatal diagnosis of Freeman-Sheldon syndrome in son of previously undiagnosed adult male

Phenotypic spectrum of the recurrent TRPM3 p.(Val837Met) substitution in seven individuals with global developmental delay and hypotonia.

TRPM3 encodes a transient receptor potential cation channel of the melastatin family, expressed in the central nervous system and in peripheral sensory neurons of the dorsal root ganglia. The recurrent substitution in TRPM3: c.2509G>A, p.(Val837Met) has been associated with syndromic intellectual disability and seizures. In this report, we present the clinical and molecular features of seven previously unreported individuals, identified by exome sequencing, with the recurrent p.(Val837Met) variant and global developmental delay. Other shared clinical features included congenital hypotonia, dysmorphic facial features (broad forehead, deep-set eyes, and down turned mouth), exotropia, and musculoskeletal issues (hip dysplasia, hip dislocation, scoliosis). Seizures were observed in two of seven individuals (febrile seizure in one and generalized tonic-clonic seizures with atonic drops in another), and epileptiform activity was observed in an additional two individuals. This report extends the number of affected individuals to 16 who are heterozygous for the de novo recurrent substitution p.(Val837Met). In contrast with the initial report, epilepsy was not a mandatory feature observed in this series. TRPM3 pathogenic variation should be considered in individuals with global developmental delays, moderate-severe intellectual disability with, or without, childhood-onset epilepsy.

The Women West of Here: Reckoning Their Place in the Western, Pop Culture, and History

The Women West of HereReckoning Their Place in the Western, Pop Culture, and History Robert James Russell (bio) A woman on the prairie is an unwanted thing … Nothing but a burden and a tie-down, keeping the ones she loves from doing what they want to do. —Alan Le May, The Siege at Dancing Bird1 Here it is, imagine it: Blue-gray thunderclouds roil overhead, promising rain soon. The outdoor sporting pavilion is flanked on both sides by high school football game–style bleachers glinting in what's left of the Sunday afternoon sun thrusting yet through the overcast. And they are packed, the stands, filled with families and veterans and children carrying massive corndogs and Bavarian-style pretzels and sticky elephant ears trailing powdered sugar and syrupy strawberry jam behind. On either end of the pavilion, rodeo crew get things ready: calves wedged in double-digits in blue-metal holding pens, ears tagged with bright plastic, lowing frequently but with so little energy it amounts to only a subtle bowing of their head. On the other end of the pavilion, trailers sit backed up against more pens, these filled with bucks poised, touring cowboys in slim jeans and boots, sitting cross-legged on the posts and surveying the thin-yet-boisterous Click for larger view View full resolution Fig 1. Lobby card for the film The White Outlaw (1925) (Wikimedia Commons). Look how Vivian Bay needs three big ol' men to protect her from the Western wilds! With men in the lead, the whole world's ripe for the taking! crowd still taking their seats. They have uneven facial hair, deep-set eyes, jagged cheekbones, all of them. They're anemic, and in unison they spit along the ground, chew the tobacco folded under the tongues, spit again. Behind them, leading to the parking lot, are trailers, an ambulance with its EMT professionals sitting side by side along the front bumper, talking quietly, waiting. Thunder in the distance, but only the audience gasps, looks over. The cowboys ready themselves, chew and [End Page 127] spit again. One laughs, one stretches his shoulders. Piles of men in denim and leather wearing numbered tags. Carbon copy dynamos. There are no women here. Thunder again, closer this time. The announcer rides out on his sorrel. He tests the microphone, taps it with the butt of his palm, but there's no sound. Fairground rides sparkle and flare behind him, along the horizon. You can just make out the food stands: hamburgers and Philly cheesesteaks and bubble tea and BBQ of every variety. A hissing pop, static, and then the man's voice comes through the speakers, burping a jovial thanks, a welcome. Things are set in motion. A rodeo clown comes out, and he—wearing oversized pantaloons, the bare basics of a cowboy's silhouette, a tiny hat atop his bulbous red wig—shares banter with the announcer. They make jokes about Southern women, Hoosier women, women in general. How they have hardly any teeth. No teeth. How Southern men—and Hoosier men, too, he adds—are lazy. And then there's leering comments about women in the stands, about making them their wives. Almost no one laughs, and yet they double down—this is, we know, scripted anyway. Up first's the bareback bronc event. The first horse, tired from the midday heat, won't stand up in the pen, won't start. Its cowboy, frustrated, tries to get situated, to rile the horse to stand. It won't, and the announcer, impotent, struggles to improvise. But he finds a target: a group of teenage girls who've already had enough and have started to mosey out toward the parking lot—girls who, during the opening prayer and the jingoist salute to America were laughing, already plotting their escape. The announcer rides along the inside fence of the pavilion, following them. "Hey, y'all," he shouts, smiling. The teens don't pay attention, don't know he's talking at them. "Where y'all going? We're just getting started." Finally, one teen turns toward him. They've nearly made their escape, at the end of the bleachers, near...

SHORT Syndrome : An End to the Diagnostic Odyssey

SHORT Syndrome is a rare genetic condition with less than 50 cases reported worldwide. Its name is an acronym, represented by Short stature, Hyperextensibility of joints, Ocular depression, Rieger anomaly and Teething delay. Other associated features include intrauterine growth restriction, lipodystrophy, delayed bone age and progeroid appearance. Cognitive function is usually preserved. Our patient was a 7-year-old-boy, referred at 9 months old forsex chromosome mosaicism detected on his karyotype analysis. He was born term via normal vaginal delivery with a birth weight of 2.05 kg and good Apgar score. Antenatally, mother was diagnosed with diabetes mellitus not requiring insulin. From 7 months gestation, serial scans showed symmetrical intrauterine growth restriction (IUGR). Examination at birth revealed a baby small for age, with prominent ears and micrognathia. During his subsequent clinic visits, he manifested Russell-Silver-like phenotype; failure to thrive, broad forehead and triangular facies, although additional features of wrinkled skin over his hands and feet, deep set eyes, groove over his chin and large ears were also seen. Genetic studies for Russell-Silver Syndrome (RSS) and chromosomal microarray testing which was done subsequently, were both normal. His genetic condition remained elusive for many years. A clinical diagnosis of SHORT Syndrome was finally considered. Polymerase Chain Reaction (PCR) and direct sequencing method was used to analyse the targeted gene at Institute for Medical Research (IMR), Kuala Lumpur. A heterozygous mutation was detected at c.1945C&gt;T in exon 15 of PIK3R1 gene; which impairs cellular growth and proliferation. This case report discusses the differential diagnosis of a dysmorphic child with short stature with RSS -like phenotype.

Anterior Subconjunctival Anesthesia for Manual Small Incision Cataract Surgery: A Randomized Controlled Trial.

Purpose:To compare the effectiveness of anterior subconjunctival anesthesia (ASCA) with sub-tenon's anesthesia (STA) for manual small incision cataract surgery (MSICS), regarding pain, akinesia, surgeon comfort, and complications.Methods:This trial randomized 164 patients into two groups. Group 1 received ASCA, and Group 2 received STA. MSICS was performed on all patients. Any complications of anesthesia were noted before starting surgery. Patient ocular motility during surgery was scored between 0 and 4 based on the number of directions of gaze in which movement persisted. Following surgery, patients scored pain felt during surgery on a visual pain-score analog, and the surgeon graded for “discomfort” felt during surgery from 0 (Nil) to 4 (additional anesthesia needed).Results:Chemosis due to anesthesia and persistence of ocular motility in all four gaze directions were seen in all 82 patients of Group 1, but these did not prevent the surgeon from performing MSICS. Seventy-seven patients (94%) in Group 1 and 79 (96.4%) in Group 2 had no or mild pain during surgery. The surgeon had moderate-to-severe discomfort in 14 (17.2%) Group 1 patients and 3 (3.6%) Group 2 patients, most of whom had deep-set eyes or exhibited excessive eye movements. Two patients in Group 1 and one patient in Group 2 were converted to peribulbar block.Conclusion:ASCA is a safe and effective alternative for performing MSICS. It does not induce akinesia but provides adequate anesthesia for the surgery in most patients, except those with deep-set eyes, especially if displaying increased anxiety.

A DNA repair disorder caused by de novo monoallelic DDB1 variants is associated with a neurodevelopmental syndrome

The DNA damage-binding protein 1 (DDB1) is part of the CUL4-DDB1 ubiquitin E3 ligase complex (CRL4), which is essential for DNA repair, chromatin remodeling, DNA replication, and signal transduction. Loss-of-function variants in genes encoding the complex components CUL4 and PHIP have been reported to cause syndromic intellectual disability with hypotonia and obesity, but no phenotype has been reported in association with DDB1 variants. Here, we report eight unrelated individuals, identified through Matchmaker Exchange, with de novo monoallelic variants in DDB1, including one recurrent variant in four individuals. The affected individuals have a consistent phenotype of hypotonia, mild to moderate intellectual disability, and similar facies, including horizontal or slightly bowed eyebrows, deep-set eyes, full cheeks, a short nose, and large, fleshy and forward-facing earlobes, demonstrated in the composite face generated from the cohort. Digital anomalies, including brachydactyly and syndactyly, were common. Three older individuals have obesity. We show that cells derived from affected individuals have altered DDB1 function resulting in abnormal DNA damage signatures and histone methylation following UV-induced DNA damage. Overall, our study adds to the growing family of neurodevelopmental phenotypes mediated by disruption of the CRL4 ubiquitin ligase pathway and begins to delineate the phenotypic and molecular effects of DDB1 misregulation.

Phenotypic and Molecular Cytogenetic Analysis of a Case of Monosomy 1p36 Syndrome due to Unbalanced Translocation

Monosomy 1p36 syndrome is one of the most common submicroscopic deletion syndromes, which is characterized by the presence of delayed developmental milestones, intellectual disability, and clinically recognizable dysmorphic craniofacial features. The syndrome comprises 4 cytogenetic groups including pure terminal deletions, interstitial deletions, complex rearrangements, and derivative chromosomes 1 due to unbalanced translocations, where unbalanced translocations represent the least percentage of all cases of monosomy 1p36 (7%). Most patients with monosomy 1p36 due to an unbalanced translocation can be cytogenetically diagnosed using conventional techniques. However, chromosomal microarray analysis is mandatory in these cases to detect copy number variance and size of the deletion and allows for setting a phenotype-genotype correlation. Here, we studied a 1.5-year-old female patient who showed intellectual disability, delayed milestones, hypotonia, seizures, and characteristic dysmorphic features including brachycephaly, straight eyebrows, deep-set eyes, downslanting palpebral fissures, midface hypoplasia, depressed nasal bridge, long philtrum, and pointed chin. Conventional cytogenetic analysis (CCA), microarray study, and fluorescence in situ hybridization (FISH) analysis were performed. CCA showed a translocation involving chromosomes 1 and 21, 45,XX,der(1)t(1;21)(p36.32;q21.1)dn. Microarray analysis revealed copy number losses at both 1p36 and proximal 21q. FISH confirmed the presence of the 1p36 deletion, but was not performed for 21q. We have concluded that phenotype-genotype correlation for monosomy 1p36 syndrome can be performed for the fundamental clinical manifestations; however, the final aspect of the syndrome depends on composite factors. Monosomy 1p36 due to unbalanced translocation may present either classically or with additional altered features of various severity based on the copy number variations involving different chromosomes.