scholarly journals The role of an ophthalmologist in the Alström syndrome diagnosis

2019 ◽  
Vol 76 (8) ◽  
pp. 843-846
Author(s):  
Jelena Karadzic ◽  
Jelica Pantelic ◽  
Igor Kovacevic ◽  
Marija Trenkic-Bozinovic
Keyword(s):  
Early Childhood ◽  
Visual Impairment ◽  
Genetic Disorder ◽  
Single Gene ◽  
Retinal Dystrophy ◽  
Clinical Manifestations ◽  
Molecular Genetic Analysis ◽  
Chromosome 2 ◽  
Gamma Glutamyl Transpeptidase ◽  
Genetic Syndrome

Introduction. The Alstr?m syndrome (AS) is an extremely rare autosomal recessive genetic disorder, affecting fewer than 1: 1,000,000 people globally. It is a single gene disorder due to the mutation of ALMS1 on chromosome 2 (2p13). The AS affects multiple organs and systems. Approximately 800 affected individuals have been identified worldwide so far. Some cases of the AS may go unrecognized for years as many of the clinical features develop over a longer period of time. As the nystagmus and retinitis pigmentosa are the most consistent findings, usually the first visible sign and present at the early infant period, the main aim of this article is to emphasize the importance of the ophthalmologist in establishing an adequate diagnosis of this rare syndrome. Case report. This article describes a Serbian patient with the Alstr?m syndrome, whose diagnosis was genetically confirmed using the whole exome sequencing. Our patient was a 7-year-old obese male with symptoms of progressive visual impairment, photophobia and nystagmus diagnosed in early childhood. On admission, the bilateral visual acuity was poor, RE 0.06, LE 0.01, the intraocular pressure within range. The funduscopy showed central retinal pigmentation, thus suggesting cone-rod retinal dystrophy with ?bull?s eye maculopathy?. The initial laboratory work at the time of the consultation revealed the elevated triglycerides levels and hyperinsulinemia, increased transaminases and gamma-glutamyl transpeptidase serum activity, whereas the glucose and glycated hemoglobin (HbA1C) levels were normal. The bilirubin test results were normal. Overall, the clinical manifestations were absent. The patient?s cardiac function was normal and the echocardiography did not indicate any abnormalities at the time. His sensorineural hearing was normal as well. A molecular genetic analysis was performed. Two composite heterozygous mutations were discovered within the ALMS1 gene sequence. In addition to the clinical presentation, the mutation detection confirmed the initial diagnosis of the AS. Conclusion. The Alstr?m syndrome should be kept in mind in case of an obese child with photophobia, nystagmus and visual impairment present from early childhood. Fundus examination by an ophthalmologist may significantly help to establish the diagnosis of this rare genetic syndrome.

scholarly journals Variable expressivity of BEST1-associated autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a three-generation pedigree

2021 ◽  
Vol 6 (1) ◽  
pp. e000813
Author(s):  
Mariana Matioli da Palma ◽  
Maurício E Vargas ◽  
Amanda Burr ◽  
Rui Chen ◽  
Mark E Pennesi ◽  
...  
Keyword(s):  
Early Childhood ◽  
Visual Impairment ◽  
Autosomal Dominant ◽  
Visual Fields ◽  
Retinal Dystrophy ◽  
Case Series ◽  
Fundus Photography ◽  
Full Field ◽  
Variable Expressivity ◽  
Paternal Grandmother

ObjectiveAutosomal dominant vitreoretinochoroidopathy (ADVIRC) is associated with pathogenic variants in BEST1, which typically causes visual impairment in the late stage of disease. We present a pedigree with variable expressivity and the youngest case in the literature with visual impairment in early childhood.Methods and analysisThis is a retrospective, observational, case series describing multigenerational members of one family affected with ADVIRC. Patients underwent examination, ultra-widefield fundus photography and angiography, optical coherence tomography, full-field electroretinography (ffERG) and full-field perimetry.ResultsThree affected members of the pedigree, one from each successive generation, were found to harbour a mutation, c.715G>A:p.Val239Met, in BEST1. The proband characterised in this report is, to our knowledge, the youngest documented case of ADVIRC in early childhood. Yet, this patient has the most severe retinal dysfunction compared with the father and paternal grandmother, whom exhibit classic characteristics of ADVIRC. Longitudinal data from the paternal grandmother showed that there was a rapid decline in ffERG responses (photopic decline worse than scotopic) from the fourth to fifth decade of life, which correlated with severe concentric constriction of visual fields.ConclusionThis multigenerational case series provides new insights into the ADVIRC disease spectrum and rate of progression. While ADVIRC typically causes a slowly progressive disease, we show that variable phenotypic expressivity is possible among affected members of the same family with the same mutation in BEST1. Thus, ADVIRC must also be considered in the differential diagnosis of paediatric patients with severe retinal dystrophy in early childhood.

scholarly journals Oral Mucosa and Nails in Genodermatoses: A Diagnostic Challenge

2021 ◽  
Vol 10 (22) ◽  
pp. 5404
Author(s):  
Tiziana Cantile ◽  
Noemi Coppola ◽  
Vito Carlo Alberto Caponio ◽  
Daniela Russo ◽  
Paolo Bucci ◽  
...  
Keyword(s):  
Oral Mucosa ◽  
Genetic Disorder ◽  
Single Gene ◽  
Clinical Manifestations ◽  
Timely Manner ◽  
Diagnostic Challenge ◽  
Oral Potentially Malignant Disorders ◽  
Multisystem Involvement ◽  
Potentially Malignant ◽  
Clinical Pictures

Genodermatoses represent a group of uncommon, hereditary, single-gene skin disorders, characterized by multisystem involvement, heterogeneous clinical manifestations and different degrees of morbidity and mortality. Some genodermatoses may have oral mucosa and nail involvement, since the oral cavity and cutaneous organ system, including nails, share a close embryologic origin. Nail disorders can manifest with nail hypoplasia or nail hypertrophy. Clinical pictures of affected oral mucosa can be extremely heterogeneous, ranging from asymptomatic papules to painful blisters, leukokeratosis, oral papillomas and fibromas to oral potentially malignant disorders and cancerous lesions. Oral mucosa and nails pathological features may occur synchronously or not and are usually associated with other systemic and skin manifestations. In some cases, oral mucosa and nails diseases may be distinct and constitute the principal sign of the genetic disorder, in other cases they represent only a part of the puzzle for the confirmation of the diagnosis. Continued awareness of the correlation between oral mucosa and nails findings can help physicians to diagnose genodermatosis in a timely manner, allowing more effective clinical management and prevention and/or early detection of complications. This article provides an overview of all specific genodermatoses affecting both oral mucosa and nails. Moreover, the correlation between teeth and nails is summarized in tabular form.

scholarly journals Paternal Uniparental Isodisomy of Chromosome 2 in a Patient with CNGA3-Associated Autosomal Recessive Achromatopsia

2021 ◽  
Vol 22 (15) ◽  
pp. 7842
Author(s):  
Susanne Kohl ◽  
Britta Baumann ◽  
Francesca Dassie ◽  
Anja K. Mayer ◽  
Maria Solaki ◽  
...  
Keyword(s):  
Segregation Analysis ◽  
Molecular Genetic ◽  
Retinal Disease ◽  
Underlying Mechanism ◽  
Recurrence Risk ◽  
Molecular Genetic Analysis ◽  
Recessive Mutation ◽  
Chromosome 2 ◽  
Inherited Retinal Disease ◽  
Uniparental Isodisomy

Achromatopsia (ACHM) is a rare autosomal recessively inherited retinal disease characterized by congenital photophobia, nystagmus, low visual acuity, and absence of color vision. ACHM is genetically heterogeneous and can be caused by biallelic mutations in the genes CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, or ATF6. We undertook molecular genetic analysis in a single female patient with a clinical diagnosis of ACHM and identified the homozygous variant c.778G>C;p.(D260H) in the CNGA3 gene. While segregation analysis in the father, as expected, identified the CNGA3 variant in a heterozygous state, it could not be displayed in the mother. Microsatellite marker analysis provided evidence that the homozygosity of the CNGA3 variant is due to partial or complete paternal uniparental isodisomy (UPD) of chromosome 2 in the patient. Apart from the ACHM phenotype, the patient was clinically unsuspicious and healthy. This is one of few examples proving UPD as the underlying mechanism for the clinical manifestation of a recessive mutation in a patient with inherited retinal disease. It also highlights the importance of segregation analysis in both parents of a given patient or especially in cases of homozygous recessive mutations, as UPD has significant implications for genetic counseling with a very low recurrence risk assessment in such families.

scholarly journals Mice with mutations in Trpm1, a gene in the locus of 15q13.3 microdeletion syndrome, display pronounced hyperactivity and decreased anxiety-like behavior

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Tesshu Hori ◽  
Shohei Ikuta ◽  
Satoko Hattori ◽  
Keizo Takao ◽  
Tsuyoshi Miyakawa ◽  
...  
Keyword(s):  
Visual Impairment ◽  
Wide Spectrum ◽  
Genetic Disorder ◽  
Mutant Mice ◽  
Chromosome 15 ◽  
Microdeletion Syndrome ◽  
Visual Transduction ◽  
The Central Nervous System ◽  
Null Mutant Mice

AbstractThe 15q13.3 microdeletion syndrome is a genetic disorder characterized by a wide spectrum of psychiatric disorders that is caused by the deletion of a region containing 7 genes on chromosome 15 (MTMR10, FAN1, TRPM1, MIR211, KLF13, OTUD7A, and CHRNA7). The contribution of each gene in this syndrome has been studied using mutant mouse models, but no single mouse model recapitulates the whole spectrum of human 15q13.3 microdeletion syndrome. The behavior of Trpm1−/− mice has not been investigated in relation to 15q13.3 microdeletion syndrome due to the visual impairment in these mice, which may confound the results of behavioral tests involving vision. We were able to perform a comprehensive behavioral test battery using Trpm1 null mutant mice to investigate the role of Trpm1, which is thought to be expressed solely in the retina, in the central nervous system and to examine the relationship between TRPM1 and 15q13.3 microdeletion syndrome. Our data demonstrate that Trpm1−/− mice exhibit abnormal behaviors that may explain some phenotypes of 15q13.3 microdeletion syndrome, including reduced anxiety-like behavior, abnormal social interaction, attenuated fear memory, and the most prominent phenotype of Trpm1 mutant mice, hyperactivity. While the ON visual transduction pathway is impaired in Trpm1−/− mice, we did not detect compensatory high sensitivities for other sensory modalities. The pathway for visual impairment is the same between Trpm1−/− mice and mGluR6−/− mice, but hyperlocomotor activity has not been reported in mGluR6−/− mice. These data suggest that the phenotype of Trpm1−/− mice extends beyond that expected from visual impairment alone. Here, we provide the first evidence associating TRPM1 with impairment of cognitive function similar to that observed in phenotypes of 15q13.3 microdeletion syndrome.

scholarly journals Hereditary haemorrhagic telangiectasia: A case report

2021 ◽  
Vol 9 ◽  
pp. 2050313X2110030
Author(s):  
Asfandyar Mufti ◽  
Muskaan Sachdeva ◽  
Khalad Maliyar ◽  
Marissa Joseph
Keyword(s):  
Arteriovenous Malformations ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Hereditary Haemorrhagic Telangiectasia ◽  
Lower Lip ◽  
Recurrent Epistaxis ◽  
Receptor Like Kinase ◽  
History Of ◽  
The Right ◽  
Symptoms And Signs

Background: Hereditary haemorrhagic telangiectasia is an autosomal dominant genetic disorder characterized by abnormalities in blood vessel formation. The clinical manifestations of patients affected with hereditary haemorrhagic telangiectasia include mucocutaneous telangiectasias and visceral arteriovenous malformations. Case Summary: We report the case of a 30-year-old female diagnosed with hereditary haemorrhagic telangiectasia presenting with the classic triad of recurrent epistaxis, mucocutaneous telangiectasias and family history of hereditary haemorrhagic telangiectasia with activin receptor-like kinase 1 mutation. Upon skin examination, she was noted to have telangiectasias under left naris, inner lower lip and surface of the tongue, and a vascular malformation on the right forearm. Conclusion: Although the skin involvement and epistaxis may be mild symptoms and signs of hereditary haemorrhagic telangiectasia, timely recognition of these can ensure vigilant monitoring of potential severe complications from cerebral and pulmonary visceral arteriovenous malformations.

Nephrotic syndrome secondary to alpha-1 antitrypsin deficiency

2021 ◽  
Vol 14 (3) ◽  
pp. e240288
Author(s):  
Gabriela F Santos ◽  
Paul Ellis ◽  
Daniela Farrugia ◽  
Alice M Turner
Keyword(s):  
Nephrotic Syndrome ◽  
Membranous Nephropathy ◽  
Clinical Investigation ◽  
Genetic Disorder ◽  
Clinical Manifestations ◽  
Protective Role ◽  
Caucasian Woman ◽  
Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin Deficiency ◽  
Alpha 1 Antitrypsin

We report a 64-year-old caucasian woman diagnosed with membranous nephropathy secondary to alpha-1 antitrypsin deficiency (AATD). AATD is a rare autosomal codominant genetic disorder. Its clinical manifestations are mostly observed in the lungs, with early-onset emphysema. Nephropathy due to AATD is still very rare and only a few cohort studies have been reported. It has been recognised that alpha-1 antitrypsin has a protective role in the kidneys which enhances the possibility of development of kidney failure, such as nephrotic syndrome, in cases of AATD. Further clinical investigation is needed to understand the relationship between the development of nephropathy, namely membranous nephropathy, and AATD.

Article on Tay-Sachs Disease

2021 ◽  
pp. 475-478
Author(s):  
Bhawana. B. Bhende
Keyword(s):  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Single Gene ◽  
Genetic Defect ◽  
Premature Death ◽  
Nerve Cells ◽  
Tay Sachs Disease ◽  
Hexosaminidase A ◽  
Physical Abilities ◽  
The Brain

Tay–Sachs disease is a genetic disorder that results in the destruction of nerve cells in the brain and spinal cord..also known as GM2 gangliosidosis or Hexosaminidase A deficiency) is an autosomal recessive genetic disorder. In its most common variant known as infantile Tay-Sachs disease it presents with a relentless deterioration of mental and physical abilities which commences at 6 months of age and usually results in death by the age of four.It is caused by a genetic defect in a single gene with one defective copy of that gene inherited from each parent. The disease occurs when harmful quantities of gangliosides accumulate in the nerve cells of the brain, eventually leading to the premature death of those cells. There is currently no cure or treatment. Tay- Sachs disease is a rare disease. Other autosomal disorders such as cystic fibrosis and sickle cell anemia are far more common. TSD is an autosomal recessive genetic disorder, meaning that when both parents are carriers, there is a 25% risk of giving birth to an affected child.

Does the ADA Provide Protection Against Discrimination on the Basis of Genotype?

1995 ◽  
Vol 23 (2) ◽  
pp. 167-172 ◽  
Author(s):  
Joseph S. Alper
Keyword(s):  
Americans With Disabilities Act ◽  
Genetic Disorder ◽  
Single Gene ◽  
Genetic Discrimination ◽  
Healthy Individuals ◽  
Multifactorial Diseases ◽  
Total Incidence ◽  
Single Gene Disorders ◽  
Near Future ◽  
The U.S

As a consequence of the problems caused by genetic discrimination, federal and state law makers are being pressured to pass a legislative remedy. A primary question is whether the Americans with Disabilities Act of 1990 (ADA) applies to (1) individuals with a potentially disabling genetic disorder who are pre-symptomatic or asymptomatic and may never become ill and to (2) healthy individuals who are carriers of genetic conditions. At present, this question has relevance principally for individuals with the genotype for single gene disorders, like Huntington disease and hemochromatosis, and to asymptomatic carriers of single gene disorders such as cystic fibrosis. Although many such single gene conditions exist, the total incidence of these conditions in the U.S. population is less than 0.4 percent. However, the question concerning the applicability of the ADA will become increasingly important because genetic tests will almost certainly be developed in the near future for common multifactorial diseases like diabetes, heart disease, and certain forms of cancer.

scholarly journals Case of Small Vessel Disease Associated with COL4A1 Mutations following Trauma

2015 ◽  
Vol 7 (2) ◽  
pp. 142-147 ◽  
Author(s):  
Joao McONeil Plancher ◽  
Robert B. Hufnagel ◽  
Achala Vagal ◽  
Katrina Peariso ◽  
Howard M. Saal ◽  
...  
Keyword(s):  
Contrast Enhancement ◽  
Head Trauma ◽  
Small Vessel Disease ◽  
Genetic Disorder ◽  
Single Gene ◽  
Young Patients ◽  
Pathogenic Mutation ◽  
Small Vessel ◽  
Vessel Disease ◽  
History Of

With this case report, we would like to heighten the awareness of clinicians about COL4A1 as a single-gene disorder causing cerebral small vessel disease and describe a previously unreported pathogenic missense substitution in COL4A1 (p.Gly990Val) and a new clinical presentation. We identified a heterozygous putatively pathogenic mutation of COL4A1 in a 50-year-old female with a history of congenital cataracts and glaucoma who presented with multiple diffusion-positive infarcts and areas of contrast enhancement following mild head trauma. We believe that this presentation of multiple areas of acute brain and vascular injury in the setting of mild head trauma is a new manifestation of this genetic disorder. Imaging findings of multiple acute infarcts and regions of contrast enhancement with associated asymptomatic old deep microhemorrhages and leukomalacia in adults after head trauma should raise a high suspicion for a COL4A1 genetic disorder. Radiographic patterns of significant leukoaraiosis and deep microhemorrhages can also be seen in patients with long-standing vasculopathy associated with hypertension, which our patient lacked. Our findings demonstrate the utility of genetic screening for COL4A1 mutations in young patients who have small vessel vasculopathy on brain imaging but who do not have significant cardiovascular risk factors.

scholarly journals A rare case of discrete aortic coarctation in Williams-Beuren syndrome. Diagnostic and therapeutic considerations

2015 ◽  
Vol 37 (2) ◽  
Author(s):  
Savina Mannarino ◽  
Eitan Keizman ◽  
Michele Pasotti ◽  
Alessia Claudia Codazzi ◽  
Elisabetta De Sando ◽  
...  
Keyword(s):  
Aortic Coarctation ◽  
Genetic Disorder ◽  
Pulmonary Stenosis ◽  
Rare Event ◽  
Facial Dysmorphism ◽  
Gene Deletions ◽  
Genetic Syndrome ◽  
Surgical Interventions ◽  
Elastin Gene

Williams-Beuren syndrome (WBS) is a genetic disorder caused by elastin gene deletions, and is characterized by cardiovascular malformations, primarily including supravalvular aortic stenosis and peripheral pulmonary stenosis. We report a case of a neonate who developed severe discrete aortic coarctation, underwent multiple surgical interventions, and was subsequently diagnosed with WBS. Severe discrete aortic coarctation is a rare event in WBS newborns. An abnormally thick aortic wall is present in these patients and is the basis of the failure of the classical approach towards coarctation repair, which consists of end-to-end anastomosis as first surgical choice. Our case, and a very few similar previously documented cases, have all demonstrated recoarctation, which only aortic patch implantation was able to successfully repair. In light of this, we would also like to underline the importance of early WBS diagnosis. Therefore, even in mild syndromic phenotype such as low birth weight or facial dysmorphism that raise the suspicion of a genetic syndrome, it is advisable to perform fluorescent <em>in situ</em> hybridization analysis rather than merely karyotypic one.

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