Project description:This case report presents a rare occurrence of 49,XXXXY syndrome in a 14-month-old male, the first documented case from Nepal, highlighting several distinctive clinical features. The patient had a height and weight below the third centile at birth and exhibited dysmorphic facial features, including a flat facial profile, flat nasal bridge, broad nose, low-set ears, and clinodactyly, along with genital anomalies like micropenis and small testes. Neurologically, he demonstrated generalized hypotonia and global developmental delay. Atrial septal defect (ASD), left to right shunt, and mild tricuspid regurgitation were identified via echocardiography, adding to the complexity of the clinical presentation. Cytogenetic analysis of peripheral blood confirmed the 49,XXXXY karyotype in all 30 cells analyzed. The child also presented with a seizure episode at 11 months, a relatively uncommon manifestation in 49,XXXXY syndrome, which required symptomatic management. Neuroimaging revealed multiple abnormalities: A contrast-enhanced computed tomography scan of the head showed mild hydrocephalus, while magnetic resonance imaging (MRI) findings included mild restricted diffusion in the bilateral frontal and parietal subcortical white matter, white matter volume loss around the lateral ventricles, and previously unreported anomalies, such as aplasia of the frontal and sphenoid paranasal sinuses and aplasia of the left transverse and sigmoid dural venous sinuses. These findings emphasize the need to recognize 49,XXXXY syndrome as a separate clinical entity from Klinefelter syndrome due to its unique features and severe cognitive and physical impairments. This case underscores the importance of comprehensive genetic evaluation and individualized, multidisciplinary management strategies for patients with rare chromosomal abnormalities. Further research is warranted to better understand the syndrome's unique clinical presentations and develop optimal therapeutic interventions.
Project description:Renal leiomyosarcomas (LMS) are extremely rare neoplasms with aggressive behaviour and poor survival prognosis. The most frequent somatic events in leiomyosarcomas are mutations in TP53, RB1, ATRX and PTEN genes, chromosomal instability and chromoanagenesis. By using chromosomal microarray analysis we identified monosomy of chromosomes 3 and 11, gain of Xp (ATRX) arm and three chromoanasynthesis regions (6q21-q27, 7p22.3-p12.1 and 12q13.11-q21.2), with MDM2 and CDK4 oncogenes copy number gains, whereas no CNVs or tumor specific SNVs in TP53, RB1 and PTEN genes were observed.
Project description:DOORS syndrome is an autosomal recessive genetic neurometabolic disorder. It occurs equally in men and women. Major causes include TBC1D 24 mutations and genetic factors. Here, we discuss a 23-year-old male patient who applied to our clinic with anonychia of the toes and was diagnosed with DOORS syndrome with other accompanying clinical symptoms.
Project description:Glioneuronal tumor (GN) is one type of biphasic central nervous system (CNS) tumor that exhibits both glial and neuronal immunohistological characteristics. We report a case of glioneuronal tumor (GN) with a discovery of novel gene fusion of CLIP2-MET resulting from aberrant chromosome 7 abnormalities. The tumor exhibited typical characteristics on histological examinations. We executed an elaborate genomic study on this case including whole-exome sequencing and RNA sequencing. Genomic analysis of the tumor revealed aberrations in chromosomes 1 and 7 and a CLIP2-MET fusion. Further analysis of the upregulated genes revealed substantial connections with MAPK pathway activation. We concluded that the chromosome 7 abnormalities prompted CLIP2-MET gene fusion which successively leads to MAPK pathway activation. We deliberated that MAPK pathway activation is responsible for the oncogenesis of GN based on our case and other previously reported ones.
Project description:PurposeTo present a case of two siblings with optic atrophy associated with Wolfram Syndrome.ObservationsTwo young adult siblings presented with serious bilateral loss of vision and dyschromatopsia established in early adolescence. They were referred with a presumed diagnosis of Leber's Hereditary Optic Neuropathy. At baseline, visual acuity was 20/400 in the right eye and 20/200 in the left eye in patient A and 20/200 in both eyes in patient B, color perception tested with pseudo-isochromatic plates was 0/17 in each eye, optic discs were pale, visual field testing revealed diffuse scotomas bilaterally while electrophysiology showed delayed prominent positive deflection (P100) values in both patients. Personal history revealed Type 1 diabetes mellitus since early childhood. Patients were lost to follow-up and presented 4 years later with significant VA decrease (<20/400) and suspected hearing loss. At that point, genetic testing revealed a pathogenic variation in the WFS1 gene thus confirming the diagnosis of Wolfram syndrome. Treatment with idebenone was proposed, to which only one of the siblings agreed. The other patient remained under observation, as no known treatment for optic atrophy in Wolfram syndrome exists to date.Conclusions and importanceWolfram syndrome is a rare neurodegenerative genetic disease associated with diabetes mellitus, optic atrophy and deafness. Careful and detailed medical and family history led to appropriate testing that confirmed the diagnosis of Wolfram syndrome. To this day, there is no definite treatment for this disease, but the experimental use of idebenone has been suggested to improve visual function. Genetic testing of family members and offspring of patients is strongly recommended.
Project description:This case report describes a case of H syndrome with characteristic cutaneous hyperpigmentation, hypertrichosis, sclerodermatous thickening, and multisystem involvement such as hearing loss and heart anomaly in an Indian patient. There are around 100 cases of this rare, autosomal recessive genodermatosis reported in the literature, out of which 10 cases are from the Indian population. The aim of this paper is to increase awareness about this novel inherited form of histiocytosis and insist on the role of dermatologists to identify such patients in our population where consanguinity is prevalent.