scholarly journals Mowat-Wilson syndrome: literature review and case series

2021 ◽  
Vol 16 (3) ◽  
pp. 10-20
Author(s):  
M. Yu. Bobylova ◽  
V. S. Kakaulina ◽  
M. O. Abramov ◽  
K. Yu. Mukhin
Keyword(s):  
De Novo ◽  
Heart Defects ◽  
Case Reports ◽  
Genetic Disorder ◽  
Epileptiform Activity ◽  
Age At Onset ◽  
Case Series ◽  
Facial Dysmorphism ◽  
Absence Seizures ◽  
Atypical Absence

Mowat-Wilson syndrome (MWS) is a rare genetic disorder characterized by a combination of the following signs: 1) facial dysmorphism (wide nose, broad medial eyebrows, pronounced chin, and open mouth); 2) mental retardation; 3) abnormalities of internal organs (congenital heart defects, Hirschsprung's disease, hypospadias/cryptorchidism). The disease is associated with a heterozygous pathogenic mutation in the ZEB2 gene. More than 80 % of MWS patients are diagnosed with epilepsy, the onset of which is usually observed in infancy. Patents have focal motor seizures, atypical absence seizures, generalized convulsive seizures. Epileptic seizures are often triggered by fever; some children are resistant to therapy. MWS patients have a specific phenotype (blue eyes, fair hair, wide-based gait, frequent laughter, limited or absent expressive language) that requires differential diagnosis with Angelman syndrome (caused by a mutation in the UBE3A gene). MWS was described in 1998, but there have been no case reports in the Russian literature yet. We report 4 cases of MWS in children aged 2 to 13 years treated in the Svt. Luka's Institute of Neurology and Epilepsy. In all of these patients, we identified a heterozygous de novo deletion in the ZEB2 gene. Epilepsy was observed in all patients. Mean age at onset was 13 months. All children had focal motor seizures and atypical absence seizures. None of them had tonic-clonic seizures or status epilepticus. The analysis of electroencephalograms showed that patients with a lower index of epileptiform activity tend to have better development and vice versa: children with a high index of epileptiform activity during sleep had more severe developmental delay.

scholarly journals Acute pre-B lymphoblastic leukemia and congenital anomalies in a child with a de novo 22q11.1q11.22 duplication

2018 ◽  
Vol 21 (1) ◽  
pp. 87-91 ◽  
Author(s):  
M Vaisvilas ◽  
V Dirse ◽  
B Aleksiuniene ◽  
I Tamuliene ◽  
L Cimbalistiene ◽  
...  
Keyword(s):  
Congenital Heart ◽  
De Novo ◽  
Heart Defects ◽  
Lymphoblastic Leukemia ◽  
Snp Array ◽  
Facial Dysmorphism ◽  
Severe Intellectual Disability ◽  
Leukemic Clone ◽  
Cell Growth And Differentiation ◽  
Facial Dysmorphia

Abstract Microdeletions and microduplications are recurrent in the q11.2 region of chromosome 22. The 22q11.2 duplication syndrome is an extremely variable disorder with a phenotype ranging from severe intellectual disability, facial dysmorphism, heart defects, and urogenital abnormalities to very mild symptoms. Both benign and malignant hematological entities are rare. A male patient was diagnosed with mild facial dysmorphia, congenital heart anomalies shortly after birth and acute bowel obstruction due to malrotation of the intestine at the age of 3 years. A whole-genome single nucleotide polymorphism (SNP) array revealed a de novo 6.6 Mb duplication in the 22q11.1q11.22 chromosomal region. A year later, the patient was diagnosed with acute pre-B lymphoblastic leukemia (pre-B ALL). Five genes, CDC45, CLTCL1, DGCR2, GP1BB and SEPT5, in the 22q11.1q11.22 region are potentially responsible for cell cycle division. We hypothesized that dosage imbalance of genes implicated in the rearrangement could have disrupted the balance between cell growth and differentiation and played a role in the initiation of malignancy with a hyperdiploid leukemic clone, whereas over-expression of the TBX1 gene might have been responsible for congenital heart defects and mild facial dysmorphia.

scholarly journals Chromosome 20p Partial De Novo Duplication Identified in a Female Paediatric Patient with Characteristic Facial Dysmorphism and Behavioural Anomalies

2020 ◽  
Vol 2020 ◽  
pp. 1-6
Author(s):  
Shahzaib Khattak ◽  
Meryam Jan ◽  
Sara Warsi ◽  
Sohail Khattak
Keyword(s):  
Scientific Literature ◽  
De Novo ◽  
Heart Defects ◽  
Self Regulation ◽  
Alagille Syndrome ◽  
Copy Number Variations ◽  
Facial Dysmorphism ◽  
Limited Data ◽  
Wide Range ◽  
History Of

Copy number variations (CNVs) involving the JAG1 gene are rare and infrequently reported in the scientific literature. Recently, a generally healthy young patient presenting with a history of behavioural concerns was referred to us. Herein, we discuss the patient, a 7-year-old female possessing a 0.797 Mb microduplication within the short arm of chromosome 20 at band 12.2. The patient generates considerable curiosity due to the rarity of her case, which includes a de novo partial duplication involving the JAG1 gene. The patient exhibits a wide range of symptoms including facial dysmorphism (dolichocephaly, round face, tented philtrum, anteverted nares, and micrognathia), clinodactyly, and an inborn congenital heart defect. She presented with behavioural concerns including ADHD-I, SPD, motor clumsiness, and poor self-regulation. Deletions in JAG1 are often linked to Alagille Syndrome; however, complete duplications have not been specifically identified as disease-causing. JAG1 mutations are reported alongside various clinical features including facial dysmorphology, heart defects, vertebral abnormalities, and ocular dysmorphic features (strabismus, epicanthal folds, and slanted palpebral fissures). This particular microduplication is rare, and thus, limited data exist regarding its significance. To our knowledge, most reported duplications are larger than 0.797 Mb. This may define a critical region causing phenotypical changes in some patient cases.

scholarly journals Angelman Syndrome: Need for Further Illumination in the Theater of the Happy Puppet

2005 ◽  
Vol 5 (6) ◽  
pp. 220-222 ◽  
Author(s):  
Raman Sankar
Keyword(s):  
Molecular Diagnosis ◽  
Angelman Syndrome ◽  
De Novo ◽  
Genetic Disorder ◽  
Age At Onset ◽  
Epileptic Seizures ◽  
Febrile Seizures ◽  
Eeg Recordings ◽  
Medical Histories

Analysis of the Characteristics of Epilepsy in 37 Patients with the Molecular Diagnosis of Angelman Syndrome Galvan-Manso M, Campistol J, Conill J, Sanmarti FX Epileptic Disord 2005;7:19–25 Angelman syndrome is a genetic disorder caused by defects in the maternally inherited imprinted domain located on chromosome 15q11-q13. Most patients with Angelman syndrome have severe mental retardation, characteristic physical appearance, behavioral traits, and severe, early-onset epilepsy. We retrospectively reviewed the medical histories of 37 patients, all with the molecular diagnosis of Angelman syndrome and at least 3 years of follow-up in our neurology department, for further information about their epilepsy: age at onset, type of seizures initially and during follow-up, EEG recordings, treatments, and response. The molecular studies showed 87% deletions de novo; 8% uniparental, paternal disomy; and 5% imprinting defects. The median age at diagnosis was 6.5 years, with 20% having begun to manifest febrile seizures at an average age of 1.9 years. Nearly all (95%) had epilepsy, the majority younger than 3 years (76%). The most frequent seizure types were myoclonic, atonic, generalized tonic–clonic, and atypical absences. At onset, two patients exhibited West syndrome. EEG recordings typical of Angelman syndrome were found in 68%. Normalization of EEG appeared in 12 patients after 9 years. Control of epileptic seizures improved after the age of 8.5 years. The most effective treatments were valproic acid and clonazepam. We conclude that epilepsy was present in nearly all of our cases with Angelman syndrome and that the EEG can be a useful diagnostic tool. On comparing the severity of epilepsy with the type of genetic alteration, we did not find any statistically significant correlations.

scholarly journals RISK FACTORS, PREVALENCE AND DIAGNOSIS OF HUTCHISON GILFORD SYNDROME WITH SPECIAL REFERENCE TO CASE REPORTS

2017 ◽  
Vol 9 (5) ◽  
pp. 1
Author(s):  
Bhawana Sharma ◽  
Priyanka Sharma ◽  
S. C. Joshi
Keyword(s):  
Splice Site ◽  
De Novo ◽  
Case Reports ◽  
Genetic Disorder ◽  
Subcutaneous Fat ◽  
Point Mutations ◽  
Lamin A ◽  
Laboratory Findings ◽  
Progeria Syndrome ◽  
Hutchinson Gilford Progeria Syndrome

Progeria also known Hutchinson–Gilford progeria syndrome (HGPS), is an extremely rare genetic disorder. The prevalence of HGPS is 1 in 4-8 million newborns. Progeria causes premature, rapid aging shortly after birth present within the first year of life. Recently, de novo point mutations in the Lmna gene at position 1824 of the coding sequence have been found in persons with HGPS. Lmna encodes lamin A and C, the A-type lamins, which are an important structural component of the nuclear envelope and play a role in protein processing. The most common HGPS mutation is located at codon 608 (G608G). This mutation responsible for creating a cryptic splice site within exon 11, which deletes a proteolytic cleavage site within the expressed mutant lamin A. In Progeria, gene mutation results in the deletion of a Zmpste24/FACE1 splice site in prelamin A, preventing end terminal cleavage. The result of this point mutation can be observed by the main clinical and radiological features include alopecia, thin skin hypoplasia of nails, loss of subcutaneous fat, and osteolysis. The common symptoms of HGPS is a loss of eyebrows and eyelashes which can observed in early childhood and due to receding hairline and blading can also observed. Generally, this patient has facial character include microganthia (small jaw), craniofacial disproportion, prominent eyes, scalp veins and alopecia (loss of hair), restricted joint mobility and severe premature atherosclerosis. Laboratory findings are unremarkable, with the exception of an increased urinary excretion of hyaluronic acid. There is presently no effective therapy is available for Hutchinson-Gilford progeria syndrome (HGPS) but, it is essential to monitor carefully cardiovascular and cerebrovascular disease So, Treatment usually includes low dose aspirin which helps prevent the atherothrombotic events, stroke and heart attacks by hindering platelet aggregation

scholarly journals Liquid Presenting as Solid: A Rare Presentation of Acute Myeloid Leukaemia as a Solid Epidural Mass

2020 ◽  
Author(s):  
Varsha Gupta ◽  
Firas Ajam ◽  
Gabriella Conte ◽  
Alsadiq Al Hillan ◽  
Kadhim Al-Banaa ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Acute Myeloid Leukaemia ◽  
Myeloid Leukaemia ◽  
De Novo ◽  
Case Reports ◽  
Case Series ◽  
Lumbar Pain ◽  
Haematological Disease ◽  
Acute Myeloid

Myeloid sarcoma (MS) is a very rare malignant tumour composed of myeloblasts. It most commonly involves soft tissue, bone, periosteum and lymph nodes, but unusual presentation sites have also been reported. Typically, MS evolves concurrently with active leukaemia or following remission, when it is known as secondary MS. But rarely MS can occur de novo without evidence of concomitant haematological disease. Herein, we report an unusual case of central nervous system-MS in a patient without evidence of concomitant haematological disease. In this case, progressive thoracic and lumbar pain with paraplegia ultimately led to the diagnosis of acute myeloid leukaemia. We also conducted a PubMed search for case reports, case series and reviews of past literature regarding central nervous system-MS and report our findings.

scholarly journals Rapid-Onset Obesity with Hypoventilation, Hypothalamic, Autonomic Dysregulation, and Neuroendocrine Tumors (ROHHADNET) Syndrome: A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-17 ◽  
Author(s):  
Jiwon M. Lee ◽  
Jaewon Shin ◽  
Sol Kim ◽  
Heon Yung Gee ◽  
Joon Suk Lee ◽  
...  
Keyword(s):  
Systematic Review ◽  
Neuroendocrine Tumors ◽  
Early Recognition ◽  
Case Reports ◽  
Age At Onset ◽  
Case Series ◽  
Rapid Onset ◽  
Patient Data ◽  
Autonomic Dysregulation ◽  
Genetic Causes

Background and Aim. ROHHADNET (rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, neuroendocrine tumor) syndrome is a rare disease with grave outcome. Although early recognition is essential, prompt diagnosis may be challenging due to its extreme rarity. This study aimed to systematically review its clinical manifestation and to identify genetic causes. Materials and Methods. We firstly conducted a systematic review on ROHHAD/NET. Electronic databases were searched using related terms. We secondly performed whole exome sequencing (WES) and examined copy number variation (CNV) in two patients to identify genetic causes. Results. In total, 46 eligible studies including 158 patients were included. There were 36 case reports available for individual patient data (IPD; 48 patients, 23 ROHHAD, and 25 ROHHADNET) and 10 case series available for aggregate patient data (APD; 110 patients, 71 ROHHAD, and 39 ROHHADNET). The median age at onset calculated from IPD was 4 years. Gender information was available in 100 patients (40 from IPD and 60 from APD) in which 65 females and 35 males were showing female preponderance. Earliest manifestation was rapid obesity, followed by hypothalamic symptoms. Most common types of neuroendocrine tumors were ganglioneuromas. Patients frequently had dysnatremia and hyperprolactinemia. Two patients were available for WES. Rare variants were identified in PIK3R3, SPTBN5, and PCF11 in one patient and SRMS, ZNF83, and KMT2B in another patient, respectively. However, there was no surviving variant shared by the two patients after filtering. Conclusions. This study systematically reviewed the phenotype of ROHHAD/NET aiming to help early recognition and reducing morbidity. The link of variants identified in the present WES requires further investigation.

scholarly journals Fraternal twins with Phelan-McDermid syndrome not involving the SHANK3 gene: case report and literature review

2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Shan Li ◽  
Ke-wang Xi ◽  
Ting Liu ◽  
Ying Zhang ◽  
Meng Zhang ◽  
...  
Keyword(s):  
Clinical Features ◽  
De Novo ◽  
Genetic Disorder ◽  
Deletion Syndrome ◽  
Facial Dysmorphism ◽  
Germline Mosaicism ◽  
Third Generation Sequencing ◽  
Neurological Features ◽  
Hands And Feet ◽  
Abnormal Behaviors

Abstract Background Phelan-McDermid syndrome (PMS, OMIM#606232), or 22q13 deletion syndrome, is a rare genetic disorder caused by deletion of the distal long arm of chromosome 22 with a variety of clinical features that display considerably heterogeneous degrees of severity. The SHANK3 gene is understood to be the critical gene for the neurological features of this syndrome. Case presentation We describe one pair of boy-girl twins with a 22q13 deletion not involving the SHANK3 gene. Interestingly, the clinical and molecular findings of the two patients were identical, likely resulting from germline mosaicism in a parent. The boy-girl twins showed intellectual disability, speech absence, facial dysmorphism, cyanosis, large fleshy hands and feet, dysplastic fingernails and abnormal behaviors, and third-generation sequencing showed an identical de novo interstitial deletion of 6.0 Mb in the 22q13.31-q13.33 region. Conclusions Our case suggests that prenatal diagnosis is essential for normal parents with affected children due to the theoretical possibility of parental germline mosaicism. Our results also indicated that other genes located in the 22q13 region may have a role in explaining symptoms in individuals with PMS. In particular, we propose that four candidate genes, CELSR1, ATXN10, FBLN1 and WNT7B, may also be involved in the etiology of the clinical features of PMS. However, more studies of smaller interstitial deletions with 22q13 are needed to corroborate our hypothesis and better define the genotype-phenotype correlation. Our findings contribute to a more comprehensive understanding of PMS.

Wiedemann-Steiner Syndrome With 2 Novel KMT2A Mutations

2016 ◽  
Vol 32 (2) ◽  
pp. 237-242 ◽  
Author(s):  
Jung Min Ko ◽  
Jae So Cho ◽  
Yongjin Yoo ◽  
Jieun Seo ◽  
Murim Choi ◽  
...  
Keyword(s):  
De Novo ◽  
Genetic Disorder ◽  
Ductus Arteriosus ◽  
Developmental Dysplasia ◽  
Facial Dysmorphism ◽  
Sequencing Analysis ◽  
Self Mutilation ◽  
Small Hands ◽  
Hands And Feet ◽  
Dysplasia Of The Hip

Wiedemann-Steiner syndrome is a rare genetic disorder characterized by short stature, hairy elbows, facial dysmorphism, and developmental delay. It can also be accompanied by musculoskeletal anomalies such as muscular hypotonia and small hands and feet. Mutations in the KMT2A gene have only recently been identified as the cause of Wiedemann-Steiner syndrome; therefore, only 16 patients from 15 families have been described, and new phenotypic features continue to be added. In this report, we describe 2 newly identified patients with Wiedemann-Steiner syndrome who presented with variable severity. One girl exhibited developmental dysplasia of the hip and fibromatosis colli accompanied by other clinical features, including facial dysmorphism, hypertrichosis, patent ductus arteriosus, growth retardation, and borderline intellectual disability. The other patient, a boy, showed severe developmental retardation with automatic self-mutilation, facial dysmorphism, and hypertrichosis at a later age. Exome sequencing analysis of these patients and their parents revealed a de novo nonsense mutation, p.Gln1978*, of KMT2A in the former, and a missense mutation, p.Gly1168Asp, in the latter, which molecularly confirmed the diagnosis of Wiedemann-Steiner syndrome.

scholarly journals Psychological effects of dopamine agonist treatment in patients with hyperprolactinemia and prolactin-secreting adenomas

2019 ◽  
Vol 180 (1) ◽  
pp. 31-40 ◽  
Author(s):  
Adriana G Ioachimescu ◽  
Maria Fleseriu ◽  
Andrew R Hoffman ◽  
T Brooks Vaughan III ◽  
Laurence Katznelson
Keyword(s):  
De Novo ◽  
Case Reports ◽  
Case Series ◽  
Severe Depression ◽  
Psychiatric Disease ◽  
Control Group ◽  
Cross Sectional ◽  
Psychiatric Complications ◽  
And Behavior ◽  
Anxiety Depression

Background Dopamine agonists (DAs) are the main treatment for patients with hyperprolactinemia and prolactinomas. Recently, an increasing number of reports emphasized DAs’ psychological side effects, either de novo or as exacerbations of prior psychiatric disease. Methods Review of prospective and retrospective studies (PubMed 1976, September 2018) evaluating the psychological profile of DA-treated patients with hyperprolactinemia and prolactinomas. Case series and case reports of psychiatric complications were also reviewed. Results Most studies were cross-sectional and had a control group of healthy volunteers or patients with nonfunctioning pituitary adenomas. There were few prospective studies, with/without control group, that included small numbers of patients. Compared with controls, patients with hyperprolactinemia generally had worse quality of life, anxiety, depression and certain personality traits. Patients receiving DAs had higher impulsivity scores than normoprolactinemic controls. Impulse control disorders (ICDs) were reported in both genders, with hypersexuality mostly in men. Multiple ICDs were sometimes reported in the same patient, usually reversible after DA discontinuation. In case reports, DA therapy was temporally associated with severe depression, manic episodes or psychosis, which improved after discontinuation and administration of psychiatric medications. Gender type of DA, dose and duration of therapy did not correlate with occurrence of psychiatric pathology. Conclusion Patients with hyperprolactinemia receiving DAs may develop changes in mood and behavior regardless of prior psychiatric history. Increased awareness for ICDs, depression, mania and other types of psychosis is needed by all physicians who prescribe DAs. Larger prospective controlled clinical studies are needed to delineate prevalence, risk stratification and management.

scholarly journals Not all SCN1A epileptic encephalopathies are Dravet syndrome

Neurology ◽  
2017 ◽  
Vol 89 (10) ◽  
pp. 1035-1042 ◽  
Author(s):  
Lynette G. Sadleir ◽  
Emily I. Mountier ◽  
Deepak Gill ◽  
Suzanne Davis ◽  
Charuta Joshi ◽  
...  
Keyword(s):  
Movement Disorder ◽  
Missense Mutation ◽  
De Novo ◽  
Age At Onset ◽  
Case Series ◽  
Febrile Seizures ◽  
Epileptic Encephalopathy ◽  
Dravet Syndrome ◽  
Developmental Impairment ◽  
Hyperkinetic Movement Disorder

Objective:To define a distinct SCN1A developmental and epileptic encephalopathy with early onset, profound impairment, and movement disorder.Methods:A case series of 9 children were identified with a profound developmental and epileptic encephalopathy and SCN1A mutation.Results:We identified 9 children 3 to 12 years of age; 7 were male. Seizure onset was at 6 to 12 weeks with hemiclonic seizures, bilateral tonic-clonic seizures, or spasms. All children had profound developmental impairment and were nonverbal and nonambulatory, and 7 of 9 required a gastrostomy. A hyperkinetic movement disorder occurred in all and was characterized by dystonia and choreoathetosis with prominent oral dyskinesia and onset from 2 to 20 months of age. Eight had a recurrent missense SCN1A mutation, p.Thr226Met. The remaining child had the missense mutation p.Pro1345Ser. The mutation arose de novo in 8 of 9; for the remaining case, the mother was negative and the father was unavailable.Conclusions:Here, we present a phenotype-genotype correlation for SCN1A. We describe a distinct SCN1A phenotype, early infantile SCN1A encephalopathy, which is readily distinguishable from the well-recognized entities of Dravet syndrome and genetic epilepsy with febrile seizures plus. This disorder has an earlier age at onset, profound developmental impairment, and a distinctive hyperkinetic movement disorder, setting it apart from Dravet syndrome. Remarkably, 8 of 9 children had the recurrent missense mutation p.Thr226Met.

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