Successful percutaneous stenting of coarctation of the aorta in Turner syndrome – a case report and literature review

Turner syndrome (TS) is the most common chromosomal abnormality affecting females and cardiac abnormalities have been described in up to 50% of patients. Although coarctation represents one of the most frequent cardiac malformation, treatment options in these patients represent an area of debate, due to associated aortopathy and risk for aortic dissection. In addition to the contradictory data found in the literature, regarding the safety profile and utility of stenting of coarctation of the aorta in TS patients, we present the case of a patient of pediatric age, who successfully underwent the procedure, being free from periprocedural and short-term complications. Beside the presentation itself, we aimed to review and summarize the data available in the literature regarding this topic. As a conclusion, we emphasize the role of minimally invasive interventional therapy and wish to underline the need of further, larger scale studies and guidelines in this patient group. Given the related aortopathy, all preventive measures should be undertaken to avoid aortic dissection during stent implantation in this vulnerable population. Although the evolution of our patient was favorable, data found in the literature is somewhat contradictory and a close follow-up is indicated to help evaluate the risk of long-term complications.

Sindroame autoinflamatorii granulomatoase asociate cu NOD2 – o scurtă actualizare pentru clinicieni

NOD2 (nucleotide-binding oligomerization domain-2), un receptor de recunoaștere a tiparelor moleculare, este implicat în apărarea imună înnăscută împotriva agenților patogeni, în integritatea mucoasei intestinale, compoziția microbiomului intestinal, autofagie, homeostazia imună și inflamație. Mutațiile NOD2 au fost asociate în primul rând cu boli ale copilului (sindromul Blau și sarcoidoza cu debut precoce, boala Crohn monogenică), dar și cu boli ale adultului (sindromul autoinflamator asociat NOD2 – NAID, denumit și sindrom Yao, etc.). S-au descris și forme intermediare între sindromul Blau și NAID. Sindromul Blau și sarcoidoza cu debut precoce sunt formele familială și, respectiv, sporadică ale unei boli rare autoinflamatorii monogenice, cu transmitere autozomal dominantă. Sindromul Blau debutează în copilăria mică, evoluând cu artrită granulomatoasă fără cazeificare, cu tenosinovită proeminentă, cu o erupție maculo-papulară sau ihtioziformă cu tentă bronzată, uveită și febră intermitentă. Pot să fie prezente și o febră periodică, limfadenopatie generalizată, precum și afectare viscerală granulomatoasă. Terapia constă din corticosteroizi, terapii imunosupresoare „de fond“ și eventual terapii biologice. La adulți, sindromul NAID sau Yao evoluează cu pusee de inflamație sistemică, cu tumefierea membrelor inferioare, tenosinovită și artrită neerozivă, febră și dermatită. Discutăm și diagnosticul diferențial cu alte boli rare granulomatoase. Creșterea informării privind aceste patologii rare autoinflamatorii, care pot să altereze calitatea vieții și să determine dizabilitate, este necesară cu scopul de a le ameliora prognosticul.

NOD2-associated granulomatous autoinflammatory syndromes – a short update for clinicians

NOD2 (nucleotide-binding oligomerization domain-2), a pattern recognition receptor, is involved in innate immune defense against pathogens, intestinal mucosal barrier integrity, gut microbiota composition, autophagy, immune homeostasis and inflammation. NOD2 mutations have been associated primarily with childhood diseases (Blau syndrome and sarcoidosis with early-onset, monogenic Crohn’s disease), but also with adult diseases (NOD2-associated autoinflammatory syndrome – NAID, also called Yao syndrome etc.). Intermediate forms between Blau syndrome and NAID have also been described. Blau’s disease and early-onset sarcoidosis are the familial and the sporadic forms respectively of a dominantly inherited rare monogenic autoinflammatory disease. Blau’s syndrome starts in early childhood, evolving with non-caseating granulomatous arthritis with prominent tenosynovitis, dermatitis with a “bronzed”, maculo-papular or scaly skin rash, and intermittent fever. Periodic fever, generalized lymphadenopathy, and granulomatous visceral involvement may be present. Therapy consists in systemic steroids, immunosuppressants and biologic drugs. In adults the NAID or Yao’s syndrome evolves with bouts of systemic inflammation with lower limbs swelling, tenosynovitis and non-erosive arthritis, fever and dermatitis. We discuss the differential diagnosis with other granulomatous diseases. Increased awareness is necessary regarding these rare diseases which may alter the quality of life or lead to disability, in order to improve their prognosis.

Bioethical aspects in type I neurofibromatosis

Type I neurofibromatosis is one of the most common monogenic disorders, being caused by abnormalities of the neurofibromin gene on chromosome 17. About half of the cases are inherited, respecting the autosomal dominant inheritance criteria, the rest are de novo cases. The clinical manifestations are multisystemic and are progressively installed, presenting inter- and intra-familial variability of clinical expression. The hereditary nature, impaired quality of life and lethal potential identify numerous and various ethical dilemmas in the diagnosis, monitoring and treatment of neurofibromatosis type 1. Variable expressiveness and multisystemic clinical manifestations determine the unpredictable evolutionary character, associating bio-ethical dilemmas necessary to be managed in the clinical context of the disease. As a clinical applicability, we conclude that some of these problems could be avoided by informing and educating affected families about the disease, by increasing confidence in specialized services and by using molecular techniques in order to know as accurately as possible the genotype-phenotype correlation.

Update in the prenatal management of sacrococcygeal teratomas and the outcome of the newborn – case report

Sacrococcygeal teratomas complicate approximatively 1 in 27,000 pregnancies, being the most common congenital germ cell tumors in infants. The diagnosis is suspected using ultrasonographic examination and confirmed after a pathology report is performed. The main issue complicating fetuses with sacrococcygeal teratomas is represented by the rapid growth and the great need of blood supply captured by the tumor that interferes with the fetal growth and fetal wellbeing, generating heart failure and, unfortunately, increasing neonatal mortality. Thus, ultrasonographic monitoring is fundamental, to diagnose, closely monitor the growth and vascularization of the tumor and to ameliorate the neonatal prognosis by establishing the proper time of birth. There are specialized healthcare centers that could perform in utero surgery with the aim to aid the normal growth and development of the fetus until term, when a curative surgery is performed to the newborn. In cases complicated with heart failure leading to fetal hydrops, pregnancy termination could be a valuable option for the mothers, as soon as the etiology and the stage of heart decompensation are known. We present a case of a fetal sacrococcygeal teratoma in a 36-year-old pregnant woman, an uninvestigated pregnancy that had a dreadful outcome with neonatal death.

A rare but treatable inborn error of metabolism: Arginine glycine amidinotransferase (AGAT) deficiency

AGAT deficiency is a rare and treatable autosomal recessive disorder. The symptoms are early-onset developmental mild to moderate intellectual disability, delayed speech acquisition, behavioral problems or proximal muscle weakness. Biochemical screening for creatine, creatinine and urinary guanidinoacetate and genetic tests are used for diagnosis. Electromyography may be normal or may have a myopathic pattern with low amplitude polyphasic waves. Muscle biopsy may show abnormalities including small myocytes. Creatine supplementation can fully prevent the neurological disability, if the treatment is started early in life; the muscular function improves irrespective of the supplementation moment.

DOWN SYNDROME – LONGITUDINAL STUDY OF CLINICAL EVOLUTION AND PSYCHO-SOCIAL IMPLICATIONS

Introduction. Down syndrome is the most common chromosomal disorder, with a worldwide frequency of 1 case in 700 live births. Objectives. Starting from the hypothesis that with the increased life expectancy of the patients with Down syndrome, new phenotypic changes and new dysfunctions are expected to appear, we proposed a longitudinal study to analyze their evolution over a long period of time. Material and method. This is a longitudinal study, based on retrospective research and descriptive evaluation, performed on a group of 81 patients from the case series of the Bihor Regional Center for Medical Genetics from Oradea. Results. We have identified 4 types of evolutionary trends of the clinical signs: stationary, involutive, progressive and with late onset. Conclusions. Knowledge of the natural evolution of the signs and symptoms of the disease is indispensable in the long-term monitoring of patients with Down syndrome. The birth of a child with Down syndrome is a real drama for the family with a strong emotional impact that can be prevented or mitigated by facilitating prenatal diagnosis, psychological counselling, social support and specialized genetic advice.

INNOVATIVE THERAPIES IN GENETIC DISEASES: SPINAL MUSCULAR ATROPHY

Spinal muscular atrophy is a congenital neuromuscular disease characterized by the deterioration of the motor neurons located mainly in the anterior horns of the spinal cord, leading to progressive muscle weakness and atrophy. Globally, SMA is, after cystic fibrosis, the second cause of death due to a a genetic disease in the pediatric population. Over 95% of the total cases of SMA are represented by 5q SMA, caused by biallelic mutations in the SMN1 gene (5q13.2), the rest of the SMA types being called, generically, non-5q SMA. Currently, a few genetic targeted therapies are available for 5q SMA, while other innovative therapies are still in clinical trials. Early diagnosis and treatment of 5q SMA have an essential role in preventing the onset and evolution of symptoms and can save the life of the patient and prevent debilitating sequelae. This article aims to briefly describe the cause and symptomatology of 5q SMA as well as to make a short review of the genetic therapies available for this disease.

STRESS IN CHILDREN PATHOLOGY: FROM PSYCHOSOMATICS TO MOLECULAR BIOLOGY

During childhood, 3 levels of stress were proposed: positive, tolerable and toxic. The toxic stress produced by the strong, frequent and prolonged activation of the body’s response systems is a generator of behavioral and somatic sequelae. Child abuse is present in all social media in different countries. The absence of basic care has devastating effects on social and cognitive development, as found in institutionalized children. Attachment behavior and fear memory are considered stress-related biological systems. The response to stress is driven by the dynamics of cortisol secretion and its interaction with its cellular receptor. It plays a central role in the response to aggression through the process of methylation, decreased gene expression in the hippocampus and increased response to stress. Stress treatment is variable in efficiency and involves preventive measures (family and community), at school, bullying, psychological counseling, trauma-focused psychotherapy, cognitive therapy, through music.