scholarly journals Diaphyseal and Metaphyseal Modeling Defects—Clinical Findings and Identification of WRAP53 Deficiency in Craniometadiaphyseal Dysplasia

2021 ◽  
Vol 12 ◽  
Author(s):  
Yun Hao ◽  
Xiao-Lin Wang ◽  
Jun Xiao ◽  
Chun-Lei Jiao ◽  
Xin-Yao Meng ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Autosomal Recessive Inheritance ◽  
Clinical Findings ◽  
Radiographic Examination ◽  
Tall Stature ◽  
Congenital Dislocation ◽  
Limb Deformity ◽  
Wormian Bones ◽  
Frameshift Deletion ◽  
Flat Feet

Background: Diaphyseal and metaphyseal modeling defects lead to severe changes in bone mass and shape, which are common features in osteoporosis that linked to non-vertebral fractures. Original mechanism of diaphyseal and metaphyseal modeling defects has proved elusive. Studying rare syndromes can elucidate mechanisms of common disorders and identify potential therapeutic targets.Methods: We evaluated a family pedigree with craniometadiaphyseal dysplasia (CRMDD, OMIM 269300), a genetic disorder that is characterized by cortical-bone thinning, limb deformity, and absent of normal metaphyseal flaring and diaphyseal constriction. Systemic radiographic examination and serum hormone test were made for this rare disease. One patient and her two normal parents were examined by means of whole-exome sequencing (WES) to identify the candidate pathogenic gene and rule out mucopolysaccharidosis and Prader–Willi Syndrome by means of Sanger sequencing.Results: There are several conspicuous radiographic characteristics: (1) bullet-shaped phalanges, (2) long and narrow pelvic inlet, absent of supra-acetabular constriction, (3) round rod-shaped long tubular bones, (4) prominent aiploic mastoid, (5) bending-shaped limb, genua varus and genu varum, and (6) congenital dislocation of elbow. Here, we did not find any wormian bones, and there are several typical clinical characteristics: (1) macrocephaly and wide jaw, (2) Avatar elf-shaped ears, pointed and protruding ears, (3) hypertrophy of limbs, (4) flat feet and giant hand phenomenon, (5) nail dystrophy, (6) limb deformity, (7) high-arched palate, (8) superficial hemangiomas, (9) tall stature, and intellectual disability. In this patient, we found biallelic frameshift deletion mutations in WRAP53, and those two mutations were transmitted from her parents respectively.Conclusions: We describe her clinical and radiological findings and presented a new subtype without wormian bones and with a tall stature. Our study showed that craniometadiaphyseal dysplasia was caused by a deficiency of WRAP53 with autosomal recessive inheritance.

Exclusive Neurogenic Bladder and Fecal Incontinency in an Achondroplasic Child Successfully Treated with Lumbar Foraminal Decompression

2021 ◽  
pp. 1-6
Author(s):  
Flavio Giordano ◽  
Matteo Lenge ◽  
Pierarturo Donati ◽  
Lorenzo Mongardi ◽  
Gianpiero Di Giacomo ◽  
...  
Keyword(s):  
Fecal Incontinence ◽  
Neurogenic Bladder ◽  
Genetic Disorder ◽  
Motor Impairment ◽  
Foramen Magnum ◽  
Clinical Findings ◽  
Lumbar Stenosis ◽  
Endochondral Bone ◽  
Case Presentation ◽  
First Case

<b><i>Introduction:</i></b> Achondroplasia is a genetic disorder characterized by defects in the development of endochondral bone resulting in skeletal abnormalities like stenosis of the foramen magnum and of the spine, shortened limb bones, and macrocephaly. Congenital spinal stenosis is frequent and due to premature fusion of the pedicles to the laminae. <b><i>Case Presentation:</i></b> We report a case of neurogenic bladder and fecal incontinence due to lumbar stenosis successfully treated with L1–L5 partial laminectomy and foraminotomy in a 7-year-old achondroplasic child. <b><i>Discussion/Conclusion:</i></b> To our knowledge, this is the first case report of exclusive neurogenic bladder and fecal incontinence in an achondroplasic child. Neurogenic bladder and fecal incontinence without motor impairment may be early and exclusive clinical findings of lumbar stenosis in children with achondroplasia.

scholarly journals Chediak-Higashi Syndrome in Accelerated Phase, a Case Report

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Artriz R
Keyword(s):  
Hemophagocytic Syndrome ◽  
Respiratory Infections ◽  
Autosomal Recessive Inheritance ◽  
Oculocutaneous Albinism ◽  
Clinical Findings ◽  
Genetic Abnormalities ◽  
History Of ◽  
Chediak Higashi Syndrome ◽  
Lysosomal Transport ◽  
Pro Inflammatory Cytokines

Chediak-Higashi syndrome corresponds to a series of genetic abnormalities in lysosomal transport, of autosomal recessive inheritance, characterized by partial oculocutaneous albinism and recurrent infections,1 usually between 7 and 10 years of age the accelerated phase of the disease, where developing hemophagocytic syndrome, given by a set of clinical findings, laboratory and histological studies where phagocytosis is prominent,2 with a failure in the regulation of the immune system due to an excessive production of pro-inflammatory cytokines that coexists with a dysfunction of natural killer cells and T lymphocytes, which leads to lethal development. We present a case of a 13-month-old patient, natural and from Pregonero, with a family history of consanguinity, recurrent respiratory infections, and a characteristic phenotype of Chediak-Higashi syndrome, without prior diagnosis or controls for this pathology, who presents with hemophagocytic syndrome leading to its death in 20 days.

Three Patients with CPT1A Deficiency: Literature Review and Case Series

2020 ◽  
Author(s):  
Naser Ali Mirhosseini ◽  
Mahdieh Saatchi ◽  
Sana Taghiyar
Keyword(s):  
Genetic Disorder ◽  
Case Series ◽  
Autosomal Recessive Inheritance ◽  
Abnormal Liver Function Test ◽  
Medical Procedures ◽  
Main Method ◽  
Appropriate Treatment ◽  
Liver And Kidney ◽  
Renal Tubular

Background: Carnitine palmitoyltransferase 1A deficiency is a rare genetic disorder with autosomal recessive inheritance pattern of fatty acid metabolism secondary to CPT1A mutation. Several dozen infants and children have been described with a deficiency of the liver and kidney CPT1 isoenzyme (CPT1-A). Clinical manifestation includes fasting-induced hypoketotic hypoglycemia, occasionally with extremely abnormal liver function test (LFT) and rarely with renal tubular acidosis. Acyl carnitine analysis has been the main method for the diagnosis of CPT1A deficiency.  Prompt treatment of hypoglycemia includes intravenous fluid containing 10% dextrose. To prevent hypoglycemia, infants should eat frequently during the day and have cornstarch continuously at night. Fasting should not last more than 12 hours during illness, surgery, or medical procedures. Case Presentation: We reported three patients with CPT1A deficiency presented with hypoglycemia and Reye like syndrome in early childhood that with early diagnosis and treatment they are well in follow-up. Conclusion: Prognosis of this genetic disorder will be good with appropriate treatment.

Spontaneous intracranial hemorrhage and multiple intracranial aneurysms in a patient with Roberts/SC phocomelia syndrome

2011 ◽  
Vol 8 (5) ◽  
pp. 460-463 ◽  
Author(s):  
Anthony C. Wang ◽  
Joseph J. Gemmete ◽  
Catherine E. Keegan ◽  
Cordelie E. Witt ◽  
Karin M. Muraszko ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Autosomal Recessive Inheritance ◽  
Inheritance Pattern ◽  
Craniofacial Malformation ◽  
Ct Angiogram ◽  
Preoperative Ct ◽  
History Of ◽  
Spontaneous Intracranial Hemorrhage

Roberts/SC phocomelia syndrome (RBS) is a rare but distinct genetic disorder with an autosomal recessive inheritance pattern. It has been associated with microcephaly, craniofacial malformation, cavernous hemangioma, encephalocele, and hydrocephalus. There are no previously reported cases of RBS with intracranial aneurysms. The authors report on a patient with a history of RBS who presented with a spontaneous posterior fossa hemorrhage. Multiple small intracranial aneurysms were noted on a preoperative CT angiogram. The patient underwent emergency craniotomy for evacuation of the hemorrhage. A postoperative angiogram confirmed the presence of multiple, distal small intracranial aneurysms.

Wormian bones in osteogenesis imperfecta: Correlation to clinical findings and genotype

2010 ◽  
Vol 152A (7) ◽  
pp. 1681-1687 ◽  
Author(s):  
Oliver Semler ◽  
Moira S Cheung ◽  
Francis H Glorieux ◽  
Frank Rauch
Keyword(s):  
Osteogenesis Imperfecta ◽  
Clinical Findings ◽  
Wormian Bones

Bilateral tibial agenesis and syndactyly in a cat

2016 ◽  
Vol 29 (04) ◽  
pp. 277-282
Author(s):  
Carla Murino ◽  
Giovanni Della Valle ◽  
Gerardo Fatone ◽  
Francesco Di Dona
Keyword(s):  
Congenital Anomaly ◽  
Clinical Findings ◽  
Abnormal Development ◽  
Case Description ◽  
Limb Deformity ◽  
Radiographic Findings ◽  
Limb Deformities ◽  
Congenital Limb ◽  
Pelvic Limb ◽  
Congenital Limb Deformities

SummaryCase description: A three-year-old cat was referred to the Veterinary Teaching Hospital, University of Naples, Italy. The cat had severe pelvic limb deformity, and abnormal development of all four paws.Clinical findings: Radiographs revealed bilateral tibial agenesis, syndactyly, and digital hypoplasia.Treatment and outcome: No treatment was instituted because of the severity of the injury, the adaptation of the cat to the abnormal condition, and the owner's refusal to permit any treatment.Clinical relevance: Congenital limb deformities are rarely reported in the cat and tibial agenesis is considered a very rare disease. This congenital anomaly is well documented and classified in man, and it has been associated with other abnormalities in more complex syndromes. This paper reports clinical and radiographic findings in a cat affected by bilateral complete tibial agenesis associated with other congenital anomalies.

scholarly journals Genetic testing for retinitis punctata albescens/fundus albipunctatus

2017 ◽  
Vol 1 (s1) ◽  
pp. 96-98
Author(s):  
Andi Abeshi ◽  
Pamela Coppola ◽  
Tommaso Beccari ◽  
Munis Dundar ◽  
Fabiana D’Esposito ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Autosomal Recessive Inheritance ◽  
Field Testing ◽  
Clinical Findings ◽  
Ophthalmological Examination ◽  
Visual Field Testing ◽  
Fundus Albipunctatus ◽  
Retinitis Punctata Albescens

Abstract We studied the scientific literature and disease guidelines in order to summarize the clinical utility of genetic testing for retinitis punctata albescens/fundus albipunctatus (RPA/FA). RPA and FA are reported to have autosomal dominant or autosomal recessive inheritance and are associated with variations in the PRPH2, RHO, RLBP1 and RDH5 genes. There is insufficient data to establish their prevalence. Clinical diagnosis is based on clinical findings, ophthalmological examination, optical coherence tomography, visual field testing and undetectable or severely reduced electroretinogram amplitudes. The genetic test is useful for confirming diagnosis, and for differential diagnosis, couple risk assessment and access to clinical trials.

scholarly journals A Novel Homozygous USP53 Splicing Variant Disrupting the Gene Function that Causes Cholestasis Phenotype and Review of the Literature

2021 ◽  
Author(s):  
ALPER GEZDIRICI ◽  
ÖZLEM KALAYCIK ŞENGÜL ◽  
MUSTAFA DOĞAN ◽  
BANU YILMAZ ÖZGÜVEN ◽  
EKREM AKBULUT
Keyword(s):  
Amino Acids ◽  
Splice Variant ◽  
Tertiary Structure ◽  
Stop Codon ◽  
Molecular Genetic ◽  
Autosomal Recessive Inheritance ◽  
Clinical Findings ◽  
Review Of The Literature ◽  
Whole Exome ◽  
Exon 1

Abstract Background: Hereditary cholestasis is a heterogeneous group of liver diseases that mostly show autosomal recessive inheritance. The phenotype of cholestasis is highly variable. Molecular genetic testing offers a useful approach to differentiate different types of cholestasis because some symptoms and findings overlap. Biallelic variants in USP53 have recently been reported in cholestasis phenotype. In this study we aim to characterize clinical findings and biological insights on a novel USP53 splice variant causing cholestasis phenotype and review of the literature. Methods and Results: We reported a novel splice variant (NM_019050.2:c.238-1G>C) in the USP53 gene via whole exome sequencing in a patient with cholestasis phenotype. This variant was confirmed by sanger sequencing and as a result of family segregation analysis; it was found to be a heterozygous state in the parents and the other healthy elder brother of our patient. According to in-silico analyses; the change in the splice region resulted in an increase in the length of exon 1, whereas the stop codon after the additional 3 amino acids (VTF) caused the protein to terminate prematurely. Thus, the mature USP53 protein, consisting of 1.073 amino acids, has been reduced to a small protein of 82 amino acids.Conclusions: We propose a model for the tertiary structure of USP53 for the first time, together with all these data, we support the association of biallelic variants of the USP53 gene with the cholestasis phenotype. We also presented a comparison of previously reported patients with the USP53-associated cholestasis phenotype to contribute to the literature.

scholarly journals Tuberculous osteomyelitis of the mandibular condyle: A rare case report and review of the literature

2021 ◽  
pp. 416-419
Author(s):  
Khushboo Bhalla ◽  
Nagaraju Kamarthi ◽  
Sangeeta S Malik ◽  
Sumit Goel ◽  
Swati Gupta ◽  
...  
Keyword(s):  
Rare Case ◽  
Mandibular Condyle ◽  
Female Child ◽  
Clinical Findings ◽  
Radiographic Examination ◽  
Rare Case Report ◽  
Tuberculous Osteomyelitis ◽  
Ear Infections ◽  
Atypical Presentations ◽  
Mycobacterium Africanum

Tuberculosis (TB) is a chronic infectious granulomatous disease caused by the air-borne bacillus Mycobacterium tuberculosis and less frequently by other bacteria in the M. tuberculosis complex (Mycobacterium Bovis and Mycobacterium africanum). Tuberculous osteomyelitis of the condyle may present atypical clinical findings akin to temporomandibular joint arthritis or middle ear infections. A detailed clinical and radiographic examination aided by a histopathological and a microbiological diagnostic workup is the key to timely detection and administration of appropriate therapeutic regimens. A high degree of clinical suspicion is thus advocated in patients with such atypical presentations. We, hereby, are presenting a rare case of tuberculous osteomyelitis in a 15-year-old female child.

Clinical findings in five Turkish patients with citrin deficiency and identification of a novel mutation on SLC25A13

2020 ◽  
Vol 33 (1) ◽  
pp. 157-163 ◽  
Author(s):  
Melis Demir Köse ◽  
Mehtap Kagnici ◽  
Taha Reşit Özdemir ◽  
Cahit Barış Erdur ◽  
Gülin Erdemir ◽  
...  
Keyword(s):  
Novel Mutation ◽  
Genetic Disorder ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Case Series ◽  
Clinical Findings ◽  
First Case ◽  
Age Related ◽  
Citrin Deficiency ◽  
Turkish Patients

AbstractBackgroundCitrin deficiency (CD) is an autosomal recessive genetic disorder caused by a defect in the mitochondrial aspartate/glutamate antiporter, citrin. Three clinical manifestations have been described until today.Case presentationWe reported 5 CD patients from two families. Four patients were male and one patient was female. Two of them have NICCD (neonatal intrahepatic cholestasis caused by citrin deficiency); three of them have CTLN2 (adult-onset type II citrullinemia). Both NICCD patients showed typical clinical and biochemical changes with a diagnosis confirmed by mutations in the SLC25A13 gene. We detected a previously unreported homozygous novel mutation c.478delC (L160Wfs*36 ) on the SLC25A13 gene. All of the CTLN2 patients were siblings. Proband was a 15-year-old mentally retarded and autistic male who had admitted to our emergency with disorientation. Laboratory data showed hyperammonemia and citrullinemia.ConclusionsTwo different profiles of age-related CD have been depicted with this article. It has been aimed to underline that the CD can be observed in different forms not only in neonatals or little infants but also in adolescents. This article is the first case series that covers both NICCD and CTLN2 cases together and that has been published in Turkey. Considering the fact that especially the majority of CTLN2 cases have been identified in Asian countries, our article has vital importance in terms of defining phenotypic features of the disease.

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