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Costello syndrome is an autosomal dominant condition caused by variants in the HRAS gene. Cardiac presentation includes valvular disease (usually valvar pulmonary stenosis), arrhythmias, and hypertrophic cardiomyopathy. To our knowledge, this is the first such report of dysplastic mitral valve associated with Costello syndrome.

This article focuses on J. M. Coetzee’s exploration of character in Foe and Elizabeth Costello, employing the metaphor of a “shipwreck” to depict the breakdown of traditional realism in literature. It examines how characters “drift” in the expanse between material reality and symbolic representation. This exploration hinges on the dual interpretations of “character”—as both a literal mark or signifier and a figurative embodiment of personhood. The discussion commences with Robinson Crusoe, positing that “drift” has been an inherent characteristic of literary characters since the inception of the novelistic tradition. The article then delves into Coetzee's nuanced narrative style, demonstrating how his characters, adrift on a sea of language and symbolism, strive to maintain their authentic existence against the encroaching tide of linguistic abstraction. This metaphorical “drift” and “shipwreck” mirror broader philosophical and cultural shifts in literature, where characters constantly oscillate between their roles as tangible entities and constructs within narrative frameworks. Coetzee’s works are shown to exemplify this tension, presenting characters who are not only vital to the storyline but also serve as metaphors for the enduring human quest for meaning and reality amid the fluidity of language and fiction.

Costello syndrome (CS) is a rare disease with intellectual disability, characterized by failure to thrive, short stature, joint laxity, loose soft skin, and distinctive facial features. This disease is caused by heterozygous germline mutations in the HRAS proto-oncogene. Cardiac and neurological abnormalities are the most common. Cardiovascular manifestations include valvular pulmonary stenosis, arrhythmia and hypertrophic cardiomyopathy. Neurological manifestations are dominated by hydrocephalus, seizures, and tethered spinal cord. Respiratory system manifestations have been reported in people with CS, but a full description of the different lung involvement and respiratory symptoms in these patients is not available. We report the case of a 19-year-old non-smoking man, followed for a Costello syndrome since the age of 8 months, who complained of exertional dyspnea and chest pain for over 18 months. The chest CT scan showed bullous emphysema of the left lung with a giant bulla in the left upper lobe measured than 20 cm long axis responsible for passive atelectasis. Pulmonary function tests revealed a severe non-reversible obstructive ventilatory defect. Faced with the worsening of his dyspnea despite treatment with bronchodilators and recurrent respiratory infections, it was decided to surgically remove the the giant emphysematous bulla. After bullectomy, a clinical and functional respiratory improvement was noted.

Background: Costello syndrome (CS) is a rare genetic syndrome in which, due to the occurrence of a mutation in the HRAS gene on chromosome 11 that causes the manifestation, a set of features such as a characteristic appearance, many congenital defects, intellectual disability and a genetic predisposition to cancer, friendly personality, and others can be identified. CS is very rare, with an incidence of ~1/300,000, but it belongs to one of the largest groups of congenital syndromes, called RASopathies, occurring with an incidence of 1/1000 people. Scoliosis and kyphosis, as well as other spinal defects, are common, in 63% and 58% of patients, respectively, and a study conducted among adult patients showed the presence of scoliosis in 75% of patients; there may be excessive lordosis of the lumbar section and inverted curvatures of the spine (lordosis in the thoracic section and kyphosis in the lumbar section). The aim of our study is to present a case report of treatment of severe scoliosis of 130 degrees in a 14-year-old patient with Costello syndrome, with coexisting Chiari II syndrome and syrinx in the absence of skeletal maturity. This patient underwent foramen magnum decompression 3 months before planned surgical correction for severe scoliosis. The patient was qualified for surgical treatment using magnetically controlled growing rods (MCGR). After spine surgery using MCGR, we gradually performed MCGR distraction over the next 2 years; we performed the final surgery, conversion to posterior spinal fusion (PSF) with simultaneous multi-level Ponte osteotomy, which gave a very good and satisfactory surgical result. In the perioperative period, two serious complications occurred: pneumothorax caused by central catheter and gastrointestinal bleeding due to previously undiagnosed gastrointestinal varices. This case shows that the treatment of severe and neglected scoliosis is complicated and requires special preparation and a surgical plan with other cooperating specialists. The scoliosis was corrected from 130 degrees to approximately 48 degrees, sagittal balance was significantly improved, and the surgical outcome was very pleasing, significantly improving quality of life and function for the patient.

Patients with a complex problem set involving multiple levels of altered structure challenge the clinician to develop an individualized, appropriate treatment plan. Dentofacial deficiency, occlusal problems, and loss of tooth structure require intervention to establish stability and regain function, speech, esthetics, and masticatory muscle comfort. The comprehensive examination must quantify each problem to specify the diagnosis for realistic treatment planning. The clinical case of a patient with Costello syndrome is presented to illustrate essential concepts in diagnosis and treatment of complex cases, including (1) Global Diagnosis of anterior esthetic relationships, (2) occlusal analysis with diagnostic casts verified in centric relation, (3) comprehensive restoration previewed with a diagnostic wax-up and removable acrylic resin overlay, (4) adhesive monobody composite resin onlays that preserve tooth structure, and (5) programmed occlusion, quantified with digital occlusal analysis, to ensure stability and comfort. Costello syndrome is a neurodevelopmental syndrome causing multisystem effects, including a distinctive craniofacial phenotype, cardiovascular disease, intellectual disability, growth hormone deficiency, and dental abnormalities such as delayed dental development, bruxism, and demineralized enamel lesions. In the present case, quantification of the patient's problem set allowed precise treatment planning that resulted in predictable restoration. [ABSTRACT FROM AUTHOR]

BackgroundAbnormal hair growth is a defining feature of RASopathies, syndromes caused by germline mutations in the RAS pathway. However, detailed hair manifestations and the mechanisms of altered hair growth in RASopathies are poorly delineated.ObjectivesTo identify distinguishing clinical features and investigate how the RAS pathway influences hair growth by performing a systematic and detailed side-by-side comparison of hair manifestations in cardio-facio-cutaneous syndrome (CFCS) and Costello syndrome (CS), two RASopathies caused by mutations in the downstream and upstream elements of the RAS pathway, respectively.MethodsSixteen individuals with CFCS and 23 individuals with CS were enrolled. Mutation data were recorded. Scalp hair, eyebrows and eyelashes of individuals with CFCS or CS were examined for texture, colour, density and morphology. Scalp hairs were examined by light microscopy.ResultsWhile both syndromes displayed abnormal hair, striking differences were observed, including darker and thicker scalp hair and sparse eyebrows and eyelashes in CFCS. By contrast, synophrys, trichomegaly and abnormalities of the scalp hair shafts were observed in CS. Possible correlation with straight hair and genotype was observed in CS.ConclusionThe results emphasize the role of the RAS pathway in hair growth, improve accuracy of clinical diagnosis of CFCS and CS and provide a foundation for identification of therapeutic targets.

Costello syndrome (CS) is a RASopathy caused by activating germline mutations in HRAS. Due to ubiquitous HRAS gene expression, CS affects multiple organ systems and individuals are predisposed to cancer. Individuals with CS may have distinctive craniofacial features, cardiac anomalies, growth and developmental delays, as well as dermatological, orthopedic, ocular, and neurological issues; however, considerable overlap with other RASopathies exists. Medical evaluation requires an understanding of the multifaceted phenotype. Subspecialists may have limited experience in caring for these individuals because of the rarity of CS. Furthermore, the phenotypic presentation may vary with the underlying genotype. These guidelines were developed by an interdisciplinary team of experts in order to encourage timely health care practices and provide medical management guidelines for the primary and specialty care provider, as well as for the families and affected individuals across their lifespan. These guidelines are based on expert opinion and do not represent evidence-based guidelines due to the lack of data for this rare condition.

This article develops the ethico‐political figure of the "cry" as a way of attending to the suffering of those on the underside of humanism. The author begins from the diagnosis that humanism—a worldview centered on the irreducible dignity of the human being by virtue of their humanity—is at an "impasse," in the way that Lauren Berlant uses the term. That is, the fantasies of a fully realized liberal humanism seem increasingly costly, while alternatives feel out of reach. Turning to J. M. Coetzee's novel Elizabeth Costello, specifically its chapters on the lives of animals, the author revamps work on the ethics of vulnerability to offer one way of negotiating this impasse without necessarily resolving it. Beginning from the moment when the novel's protagonist describes the effects of a hen's cry as she is put to death, the article posits the cry as the irruption of vulnerability that is proper neither to animality or humanity. Irreducible to voice or speech, the cry is a quivering movement that threatens the coherency of vocal capacity. Attention to it creates the possibility of becoming undone, of reorienting maps of suffering, and of entering into new relationships with those on the underside of hegemonic humanism. [ABSTRACT FROM AUTHOR]

Chiara Leoni,1 Germana Viscogliosi,1 Marco Tartaglia,2 Yoko Aoki,3 Giuseppe Zampino1,4 1Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Rome, Italy; 2Genetics and Rare Diseases Research Division, Ospedale Pediatrico Bambino Gesù, IRCCS, Rome, Italy; 3Department of Medical Genetics, Tohoku University School of Medicine, Sendai, Japan; 4Università Cattolica del Sacro Cuore, Rome, ItalyCorrespondence: Chiara Leoni, Center for Rare Diseases and Birth Defects, Department of Woman and Child Health and Public Health, Fondazione Policlinico Universitario “A. Gemelli” IRCCS, Largo Gemelli 8, Rome, IT-00168, Italy, Tel +39-063381344, Fax +39-063383211, Email chiara.leoni@policlinicogemelli.itAbstract: Costello syndrome (CS) is a rare neurodevelopmental disorder caused by germline mutations in HRAS. It belongs among the RASopathies, a group of syndromes characterized by alterations in components of the RAS/MAPK signaling pathway and sharing overlapping phenotypes. Its typical features include a distinctive facial appearance, growth delay, intellectual disability, ectodermal, cardiac, and musculoskeletal abnormalities, and cancer predisposition. Due to the several comorbidities having a strong impact on the quality of life, a multidisciplinary team is essential in the management of such a condition from infancy to adult age, to promptly address any detected issue and to develop appropriate personalized follow-up protocols and treatment strategies. With the present paper we aim to highlight the core and ancillary medical disciplines involved in managing the health challenges characterizing CS from pediatric to adult age, according to literature and to our large clinical experience.Keywords: multidisciplinary team, personalized medicine, HRAS, Costello syndrome, RASopathies