scholarly journals Incidental Finding of MEGDEL Syndrome Based on Neuroimaging: Case Report

2021 ◽  
pp. 429-433
Author(s):  
Salma A. Alshammari ◽  
Fouad A. Alghamdi ◽  
Rami Alhazmi ◽  
Shaikhah Aldossary
Keyword(s):  
Incidental Finding ◽  
Molecular Genetic ◽  
Cerebellar Atrophy ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Disease Diagnosis ◽  
First Year ◽  
Pathogenic Variants ◽  
Clinical Presentations ◽  
First Year Of Life

MEGDEL 3-methylglutaconic (MG) aciduria, deafness, encephalopathy, Leigh-like syndrome is an autosomal recessive disorder associated with infantile hypoglycemia, progressive psychomotor developmental delay, cerebellar atrophy with lesions in the basal ganglia, spasticity, dystonia, deafness, and transient liver problems, which typically occur in the first year of life. Other clinical presentations include failure to thrive, epilepsy, and optic nerve atrophy. The serine active site-containing 1 (SERAC1) mutation is localized at the mitochondria-associated membranes, which are responsible for encoding a phosphatidylglycerol remodeler essential for both mitochondrial function and intracellular cholesterol trafficking and is thus responsible for the disease. Diagnosis is confirmed by the elevation of and concentrations of 3-MG acid and 3-methylglutaric acid in the urine or by identification of bi-allelic SERAC1 pathogenic variants on molecular genetic testing. Different pathological variants of SERAC1 have been identified in MEGDEL syndrome to date. Here, we report a case of a child with MEGDEL syndrome due to SERAC1 mutation. The child presented with accidental finding by CT showing hypodensity on bilateral symmetric anterior putamen and caudate abnormal. Neurological examination was unremarkable. This report presents a new neuroimaging finding by CT of MEGDEL syndrome.

Molecular Analysis of the CYP11B2 Gene in 62 Patients with Hypoaldosteronism Due to Aldosterone Synthase Deficiency

2020 ◽  
Vol 106 (1) ◽  
pp. e182-e191
Author(s):  
Christina Merakou ◽  
Irene Fylaktou ◽  
Amalia Sertedaki ◽  
Maria Dracopoulou ◽  
Antonis Voutetakis ◽  
...  
Keyword(s):  
Gene Sequencing ◽  
Failure To Thrive ◽  
In Silico Analysis ◽  
Autosomal Recessive Disorder ◽  
Molecular Study ◽  
Aldosterone Synthase ◽  
Salt Wasting ◽  
Pathogenic Variants ◽  
Novel Variants ◽  
Aldosterone Synthase Deficiency

Abstract Context Isolated congenital hypoaldosteronism presents in early infancy with symptoms including vomiting, severe dehydration, salt wasting, and failure to thrive. The main causes of this rare autosomal recessive disorder is pathogenic variants of the CYP11B2 gene leading to aldosterone synthase deficiency. Objective To investigate the presence of CYP11B2 pathogenic variants in a cohort of patients with a clinical, biochemical, and hormonal profile suggestive of aldosterone synthase deficiency. Design Clinical and molecular study. Setting Tertiary academic Children’s Hospital, Center for Rare Pediatric Endocrine Diseases. Patients and Methods Sixty-two patients (56 unrelated patients and 6 siblings), with hypoaldosteronism and their parents, underwent CYP11B2 gene sequencing after its selective amplification against the highly homologous CYP11B1 gene. In silico analysis of the identified novel variants was carried out to evaluate protein stability and potential pathogenicity. Results CYP11B2 gene sequencing revealed that 62 patients carried a total of 12 different pathogenic CYP11B2 gene variants, 6 of which are novel. Importantly, 96% of the 56 patients carried the previously reported p.T185I variant either in homozygosity or in compound heterozygosity with another variant. The 6 novel variants detected were: p.M1I, p.V129M, p.R141Q, p.A165T, p.R448C, and the donor splice site variant of intron 8, c.1398 + 1G > A. Conclusion Molecular diagnosis was achieved in 62 patients with aldosterone synthase deficiency, the largest cohort thus far reported. Six novel genetic variants were identified as possibly pathogenic, extending the spectrum of reported molecular defects of the CYP11B2 gene.

Molecular genetic diagnostics of Bardet-Biedl syndrome with an MPS-panel

2021 ◽  
pp. 26-35
Author(s):  
М.Д. Орлова ◽  
П. Гундорова ◽  
А.В. Поляков
Keyword(s):  
Autosomal Recessive ◽  
Molecular Genetic ◽  
Autosomal Recessive Disorder ◽  
Genetic Diagnostics ◽  
Bardet Biedl Syndrome ◽  
Pathogenic Variants ◽  
Development Delay ◽  
Molecular Genetic Diagnostics ◽  
First Time

Синдром Барде-Бидля - аутосомно-рецессивное заболевание, характеризующееся ожирением, пигментной дегенерацией сетчатки, полидактилией, задержкой психоречевого развития и структурными повреждениями почек. В работе представлены результаты применения МПС-панели, включающей кодирующие последовательности и прилегающие интронные области 21 гена, ассоциированного с синдромом Барде-Бидля. Впервые была проведена молекулярно-генетическая диагностика в группе из сорока российских пациентов с синдромом Барде-Бидля из неродственных семей. В результате исследования удалось подтвердить диагноз молекулярно-генетическим методом у 40% пациентов (n=16). В генах BBS1, BBS7 и BBS10 встретились повторяющиеся варианты. Частота встречаемости патогенных и вероятно патогенных вариантов в генах BBS1 и BBS10 у российских пациентов соответствует зарубежным данным. Варианты в гене BBS7 встретились у пяти человек, у четырех из них был обнаружен патогенный вариант c.1967_1968delTAinsC, не встречающийся в других популяциях. Результаты, представленные в статье, показывают значительный вклад в заболеваемость синдромом Барде-Бидля в российской популяции патогенных вариантов в гене BBS7. Bardet-Biedl syndrome is an autosomal recessive disorder characterized by obesity, retinitis pigmentosa, polydactyly, development delay, and structural kidney defects. This study shows the results of using an MPS panel that includes coding sequences and intronic areas of 21 genes associated with Bardet-Biedl syndrome. For the first time molecular genetic testing has been provided for the group of 40 Russian patiens with Bardet-Biedl syndrome from unrelated families. As a result of the testing, diagnoses were confirmed for 40% of the patients (n=16). The genes BBS1, BBS7, BBS10 had recurrent variants. The frequency of pathogenic and likely pathogenic variants in the genes BBS1 and BBS10 among Russian patients matches the research data in other countries. Variants in the BBS7 gene were found for five people, four of them had a pathogenic variant c.1967_1968delTAinsC, which is not present among other populations. Results provided in this article show the significant role of pathogenic variants in the BBS7 gene in patients with Bardet-Biedl syndrome in Russian population.

scholarly journals Neuromuscular and Neuroendocrinological Features Associated With ZC4H2-Related Arthrogryposis Multiplex Congenita in a Sicilian Family: A Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Gianluca Piccolo ◽  
Giuseppe d'Annunzio ◽  
Elisabetta Amadori ◽  
Antonella Riva ◽  
Paola Borgia ◽  
...  
Keyword(s):  
Genetic Basis ◽  
First Year ◽  
Arthrogryposis Multiplex Congenita ◽  
Neurodevelopmental Delay ◽  
Pathogenic Variants ◽  
Phenotypic Spectrum ◽  
Distal Muscle ◽  
Neurodevelopmental Impairment ◽  
First Year Of Life

Wieacker-Wolff syndrome (WWS) is an X-linked Arthrogryposis Multiplex Congenita (AMC) disorder associated with broad neurodevelopmental impairment. The genetic basis of WWS lies in hemizygous pathogenic variants in ZC4H2, encoding a C4H2 type zinc-finger nuclear factor abundantly expressed in the developing human brain. The main clinical features described in WWS families carrying ZC4H2 pathogenic variants encompass having a short stature, microcephaly, birth respiratory distress, arthrogryposis, hypotonia, distal muscle weakness, and broad neurodevelopmental delay. We hereby report a Sicilian family with a boy clinically diagnosed with WWS and genetically investigated with exome sequencing (ES), leading to the identification of a c.593G>A (p. R198Q) hemizygous pathogenic variant in the ZC4H2 gene. During the first year of life, the onset of central hypoadrenalism led to recurrent hypoglycemic events, which likely contributed to seizure susceptibility. Also, muscle biopsy studies confirmed a pathology of the muscle tissue and revealed peculiar abnormalities of the neuromuscular junction. In conclusion, we expand the phenotypic spectrum of the WWS-related neurodevelopmental disorders and discuss the role of ZC4H2 in the context of the potential neuroendocrinological and neuromuscular features associated with this condition.

scholarly journals Report of Two Novel Mutations in Indian Patients with Rothmund–Thomson Syndrome

2019 ◽  
Vol 08 (03) ◽  
pp. 163-167
Author(s):  
Sakshi Yadav ◽  
Seema Thakur ◽  
Juergen Kohlhase ◽  
Neetu Bhari ◽  
Madhulika Kabra ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Supportive Therapy ◽  
Failure To Thrive ◽  
Autosomal Recessive Disorder ◽  
Skin Lesions ◽  
Poor Growth ◽  
Pathogenic Variants ◽  
Specific Distribution ◽  
Novel Variants ◽  
Rothmund Thomson Syndrome

AbstractRothmund–Thomson syndrome (RTS) is a rare autosomal recessive disorder caused by mutations in RECQL4 and has characteristic clinical features. We report two unrelated phenotypically diverse patients (cases 1 and 2) with RTS having novel variants in RECQL4 gene. Case-1 was evaluated for poor growth and recurrent fractures and skin lesions. Case-2 presented at 4 months with failure to thrive and radial ray defect and developed poikilodermatous skin lesions after infancy. Both cases were confirmed to have homozygous pathogenic variants in RECQL4. Both patients have normal intellect and are on supportive therapy. The presence of characteristic poikiloderma lesions with specific distribution and skeletal anomalies in a patient with proportionate short stature is a clue toward the diagnosis of RTS.

Early Recognition of Infant Malignancy: The Five Most Common Infant Cancers

2003 ◽  
Vol 22 (5) ◽  
pp. 11-19 ◽  
Author(s):  
Yi-Chih Lin
Keyword(s):  
Nurse Practitioners ◽  
Early Recognition ◽  
Signs And Symptoms ◽  
Screening Tools ◽  
First Year ◽  
Optimal Care ◽  
Factors Associated ◽  
Historical Factors ◽  
Clinical Presentations ◽  
First Year Of Life

The incidence of cancer in children is rising in the U.S. Although cancer in the first year of life is relatively rare, understanding the early signs and symptoms of and the historical factors associated with most common infant cancers is essential for providing optimal care to these infants and their families. Neonatal nurses and nurse practitioners play a pivotal role in early recognition and detection of infant malignancy. This article reviews the incidence of and historical factors associated with infant cancers and discusses clinical presentations and available diagnostic images as well as screening tools for the five most common types of infant malignancy.

scholarly journals A rare case report of unusual presentation of Edward’s syndrome (trisomy 18)

2018 ◽  
Vol 5 (4) ◽  
pp. 1685
Author(s):  
Meenakshi S. Kushwah ◽  
Ajay Gaur
Keyword(s):  
Case Report ◽  
Intellectual Disability ◽  
Rare Case ◽  
Genetic Disorder ◽  
Failure To Thrive ◽  
First Year ◽  
Extra Copy ◽  
Edwards Syndrome ◽  
Rare Case Report ◽  
First Year Of Life

Edwards syndrome, a rare genetic disorder is characterized by the extra copy of chromosome 18. About 50% babies with this syndrome do not survive one week of age and approx. 95% do not survive past the first year of life. The syndrome is usually characterized by dysmorphic facies, microcephaly, flexion finger deformity and rocker- bottom feet. There is involvement of cardiacvascular and renal system with intellectual disability. Authors report a case of Edwards syndrome presenting with failure to thrive and developmental delay in the absence of usual clinical features of Edwards syndrome.

scholarly journals A rare case of Vitamin D dependent rickets type II: a case report

2019 ◽  
Vol 6 (5) ◽  
pp. 2209
Author(s):  
Raghava Badabagni ◽  
Rambabu Bodduluri ◽  
P. V. Prudhvi Raju
Keyword(s):  
Vitamin D ◽  
Vitamin D3 ◽  
Receptor Gene ◽  
Autosomal Recessive Disorder ◽  
First Year ◽  
High Dose ◽  
Type Ii ◽  
Recommended Treatment ◽  
Physiological Dose ◽  
First Year Of Life

Vitamin D-dependent type II rickets (VDDRII) is a rare autosomal recessive disorder caused by mutation in the vitamin D receptor gene, leading to end-organ resistance to 1,25(OH)2 vitamin D3. It presents with refractory rickets and growth retardation presenting in the first year of life. It is frequently associated with alopecia totalis. Due to target organresistance, its response to vitamin D is poor. The recommended treatment is giving supra physiological dose of 1,25(OH)2 vitamin D3 and a high dose of oral or intravenous calcium. The response of alopecia to treatment is generally poor. We present a 3 ½ year-old male child with VDDR II whose alopecia and rickets partially responded to 1,25(OH)2 vitamin D3.

scholarly journals 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency: One disease- many faces

2020 ◽  
Author(s):  
Sarah Catharina Grünert ◽  
Jörn Oliver Sass
Keyword(s):  
Autosomal Recessive ◽  
Coenzyme A ◽  
Autosomal Recessive Disorder ◽  
First Year ◽  
Metabolic Decompensation ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Lyase Deficiency ◽  
First Year Of Life

Abstract Background 3-hydroxy-3-methylglutaryl-coenzyme A lyase deficiency (HMGCLD) is an autosomal recessive disorder of ketogenesis and leucine degradation due to mutations in HMGCL . Method We performed a systematic literature search to identify all published cases. 211 patients of whom relevant clinical data were available were included in this analysis. Clinical course, biochemical findings and mutation data are highlighted and discussed. An overview on all published HMGCL variants is provided. Results More than 95 % of patients presented with acute metabolic decompensation. Most patients manifested within the first year of life, 42.4 % already neonatally. Very few individuals remained asymptomatic. The neurologic long-term outcome was favorable with 62.6 % of patients showing normal development. Conclusion This comprehensive data analysis provides a systematic overview on all published cases with HMGCLD including a list of all known HMGCL mutations.

scholarly journals Simultaneous Identification of Both MFSD8 and RDH12 Pathogenic Variants in a Chinese Family Affected With Retinitis Pigmentosa

2021 ◽  
Vol 12 ◽  
Author(s):  
Yihui Wang ◽  
Yanling Teng ◽  
Desheng Liang ◽  
Zhuo Li ◽  
Lingqian Wu
Keyword(s):  
Retinitis Pigmentosa ◽  
Molecular Genetic ◽  
Cerebellar Atrophy ◽  
Compound Heterozygous Mutation ◽  
Chinese Family ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Homozygous Mutation ◽  
Pathogenic Variants ◽  
Reproductive Counseling

Retinitis pigmentosa (RP) is characterized by tremendous genetic and phenotypic heterogeneity. Here, we investigate the pathogeny of RP in a family to provide evidence for genetic and reproductive counseling for families. Although this pregnant woman of 8+3 weeks presented with RP, her first baby was born with RP, epilepsy, and cerebellar atrophy. The research identified a compound heterozygous mutation (c.998+3_998+6del/deletion) in the MFSD8 gene of the first born, explaining the cause of the proband’s disease, which cannot explain the mother’s. Then, a homozygous mutation c.343+1G > A in RDH12 of the mother was found. RT-PCR is employed to find that there is a skipping of exon 10 in MFSD8 and a 15-nucleotide retention of intron5 in RDH12. The coexistence of two independent instances of RP caused by distinct genes in one pedigree is demonstrated. Based on the diagnosis, a prenatal diagnosis performed on the fetus found that the fetus’s MFSD8 is affected by the same mutation as the proband. The research underscoring the complexity of RP and the need for the combination of extensive molecular genetic testing and clinical characterization in addition expands the spectrum of MFSD8 mutations. Finally, it is expected that the family members would be prevented from reproducing children with the similar disease.

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