scholarly journals Prader-Willi Syndrome due to an Unbalanced de novo Translocation t(15;19)(q12;p13.3)

2016 ◽  
Vol 150 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Vy Dang ◽  
Abhilasha Surampalli ◽  
Ann M. Manzardo ◽  
Stephanie Youn ◽  
Merlin G. Butler ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosome Region ◽  
Genetic Disorder ◽  
Type I ◽  
Prader Willi Syndrome ◽  
Stk11 Gene ◽  
Feeding Difficulties ◽  
First Case ◽  
Increased Risk ◽  
Hands And Feet

Prader-Willi syndrome (PWS) is a complex, multisystem genetic disorder characterized by endocrine, neurologic, and behavioral abnormalities. We report the first case of an unbalanced de novo reciprocal translocation of chromosomes 15 and 19, 45,XY,-15,der(19)t(15;19)(q12;p13.3), resulting in monosomy for the PWS critical chromosome region. Our patient had several typical features of PWS including infantile hypotonia, a poor suck and feeding difficulties, tantrums, skin picking, compulsions, small hands and feet, and food seeking, but not hypopigmentation, a micropenis, cryptorchidism or obesity as common findings seen in PWS at the time of examination at 6 years of age. He had seizures noted from 1 to 3 years of age and marked cognitive delay. High-resolution SNP microarray analysis identified an atypical PWS type I deletion in chromosome 15 involving the proximal breakpoint BP1. The deletion extended beyond the GABRB3 gene but was proximal to the usual distal breakpoint (BP3) within the 15q11q13 region, and GABRA5, GABRG3, and OCA2 genes were intact. No deletion of band 19p13.3 was detected; therefore, the patient was not at an increased risk of tumors from the Peutz-Jeghers syndrome associated with a deletion of the STK11 gene.

857 Too sleepy: A pediatric case of Prader Willi Syndrome and Narcolepsy

SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A333-A333
Author(s):  
Elizabeth Lam ◽  
Sonal Malhotra ◽  
Daniel Glaze
Keyword(s):  
Daytime Sleepiness ◽  
Sleep Latency ◽  
Chromosome Region ◽  
Genetic Disorder ◽  
Sleep Onset ◽  
Apnea Hypopnea Index ◽  
Prader Willi Syndrome ◽  
Obstructive Sleep ◽  
Patient Reported

Abstract Introduction Prader Willi syndrome (PWS) is a genetic disorder due to deletion of the paternal copies of genes within the chromosome region 15q11-q13. Individuals with PWS are commonly seen with obesity, sleep disordered breathing, and excessive daytime sleepiness (EDS). While the exact cause of EDS in individuals with PWS is not fully understood, there have been reports of PWS with narcolepsy-like syndrome. We report a case of a patient with PWS with findings suggesting the diagnosis of Narcolepsy Type 2. Report of case(s) Our patient is a 12-year-old male with PWS and 2nd degree heart block who was evaluated in our pediatric sleep center. He has a previous diagnosis of mild obstructive sleep apnea (OSA) with an apnea hypopnea index (oAHI) of 3.2. At 12 years of age, mother and patient reported that he had increased snoring, weight gain, EDS with a Pediatric Daytime Sleepiness Score (PDSS) of 10 and frequent refreshing naps during the daytime. Patient denied cataplexy during that visit. Subsequently, 2-week actigrapghy was performed which demonstrated an average total night sleep of 8 hours and 8 minutes. Overnight PSG with Multiple Sleep Latency Test (MSLT) demonstrated an oAHI of 4.8, total sleep time of 6.88 hours. During the MSLT, the mean sleep latency was 6.2 minutes and 5 sleep onset REM periods were observed over 5 nap opportunities. At his follow-up visit, methylphenidate was initiated after clearance by his cardiologist. Patient and mother opted for medical management of his mild OSA with Fluticisone and Montelukast. At his follow-up appointment, the patient had improvement in daytime sleepiness with a PDSS of 2 despite taking his Methylphenidate at night. Patient was instructed to switch to morning Methylphenidate dosing to optimize treatment of his EDS. Conclusion EDS is a common complaint seen in patients with PWS, however the etiology of it is not entirely understood. It is thought to be centrally mediated with components of hypersomnia and narcolepsy like-symptoms. More research is needed to better understand, diagnose and adequately treat patients with PWS and EDS. Support (if any):

scholarly journals A Case of Persistent Foot Pain in a Neurofibromatosis Type I Patient

2012 ◽  
Vol 2012 ◽  
pp. 1-3 ◽  
Author(s):  
Vasilis Stavrinides ◽  
Salim Nasra
Keyword(s):  
Past History ◽  
Genetic Disorder ◽  
Young Male ◽  
Neurofibromatosis Type ◽  
Chromosome 17 ◽  
Type I ◽  
Foot Pain ◽  
Loss Of Function ◽  
Increased Risk ◽  
Initial Symptoms

Introduction. This is the case of a young male patient who presented to his family physician with atypical left foot pain, which was extremely resistant to analgesia and caused significant disability. Despite extensive investigations, the cause of his pain was not identified until 18 months after his initial symptoms, when the official diagnosis of malignant peripheral nerve sheath tumour (MPNST) was made. Detailed review of the patient’s past history established the diagnosis of type I neurofibromatosis (NF-1), previously undetected.Discussion. NF-1 is an autosomal dominant genetic disorder caused by loss of function mutations of theNF1gene in chromosome 17. Patients with this condition are at increased risk for developing MPNSTs which, however, are treatable only in early stages.Conclusion. Although monitoring NF-1 patients for the development of MPNSTs is common practice, the index of clinical suspicion in patients without an established NF-1 diagnosis is low. Any atypical pain in young adults should raise the possibility of this malignancy, and this case illustrates the fact that MPNSTs can be the first manifestation of NF-1 in patients previously undiagnosed with the disease.

scholarly journals Neurofibromatosis Type I and Stromal Tumor with a Multiple Digestive Localization

2021 ◽  
Vol 2021 ◽  
pp. 1-4
Author(s):  
Amina Chaka ◽  
Farouk Ennaceur ◽  
Mohamed Amine Tormen ◽  
Ibtissem Korbi ◽  
Faouzi Noomen ◽  
...  
Keyword(s):  
Genetic Disorder ◽  
Neurofibromatosis Type ◽  
Stromal Tumor ◽  
Type I ◽  
Neurofibromatosis Type I ◽  
Multisystem Disorder ◽  
Cell Tissue ◽  
Increased Risk ◽  
Recklinghausen Disease ◽  
Made In

Neurofibromatosis type I (NF1) is also known as von Recklinghausen disease. It is a genetic disorder that affects the growth and development of nerve cell tissue, which is characterized by a multisystem disorder and an increased risk for cancer. The incidence of gastroduodenal stromal tumor during Recklinghausen disease can reach 35% in autopsies and 5% in clinical cases. In our case, the diagnosis of neurofibromatosis type I was made in a middle-aged women initially diagnosed with a pancreaticoduodenal tumor.

scholarly journals Whole genome analysis of an extended pedigree with Prader–Willi Syndrome, hereditary hemochromatosis, and dysautonomia-like symptoms

2015 ◽  
Author(s):  
Han Fang ◽  
Yiyang Wu ◽  
Margaret Yoon ◽  
Laura T. Jiménez-Barrón ◽  
Jason A. O'Rawe ◽  
...  
Keyword(s):  
De Novo ◽  
Chromosome Region ◽  
Hereditary Hemochromatosis ◽  
Copy Number Variations ◽  
Prader Willi Syndrome ◽  
Whole Genome ◽  
Whole Genome Analysis ◽  
Phenotypic Data ◽  
Human Phenotype ◽  
Congenital Insensitivity

This report includes the discovery and analysis of a pedigree with Prader–Willi Syndrome (PWS), hereditary hemochromatosis (HH), and dysautonomia-like symptoms. Nine members of the family participated in whole genome sequencing (WGS), which enabled a wide scope of variant calling from single-nucleotide polymorphisms to copy number variations. First, a 5.5 Mb de novo deletion is identified in the chromosome region 15q11.2 to 15q13.1 in the boy with PWS. Second, a female invididual with HH is homozygous for the p.C282Y variant in HFE, a mutation known to be associated with HH. Her brother is homozygous for the same variant, although he has yet to be clinically diagnosed with HH. Third, none of the people with dysautonomia-like symptoms carry any reported or novel rare variants in IKBKAP that are implicated in familial dysautonomia (FD - HSAN III). Although two people with dysautonomia-like symptoms carry two heterozygous variants in NTRK1, a gene that has been shown to contribute to HSAN IV (congenital insensitivity to pain with anhidrosis, a disease that closely resembles FD), this variant is not present in the third proband. Fourth, WGS revealed pharmacogenetic variants influencing the metabolism of warfarin and simvastatin, which are being routinely prescribed to the proband. Finally, reports of the phenotypes were standardized with the Human Phenotype Ontology annotation, which may facilitate the search for other families with similar phenotypes. Due to the extreme heterogeneity and insufficient knowledge of human diseases, it is of crucial importance that both phenotypic data and genomic data are standardized and shared.

scholarly journals Apert Syndrome: A Rare Genetic Disorder

2021 ◽  
Vol 11 (2) ◽  
pp. 475-477
Author(s):  
Mahmuda Hassan ◽  
B H Nazma Yasmeen ◽  
Masuma Khan ◽  
Afsana Mukti
Keyword(s):  
Genetic Disorder ◽  
The Body ◽  
Apert Syndrome ◽  
Type I ◽  
Fibroblast Growth Factor Receptors ◽  
Rare Type ◽  
Medical College ◽  
Branchial Arches ◽  
Maxilla And Mandible ◽  
Hands And Feet

Apert syndrome is a rare type I acrocephalosyndactyly syndrome having autosomal dominant inheritance due to mutations in the fibroblast growth factor receptors gene. New or fresh mutations are also frequent. It is characterized by dysmorphic face, craniosynostosis, severe syndactyly of the hands and feet. Apert syndrome affects the first branchial or pharyngeal arch, the precursor of the maxilla and mandible. Disturbances in the development of branchial arches during fetal period create extensive malformation in different parts of the body. Management of Apert syndrome requires a multidisciplinary approach. We, hereby, report a case of a 45-days old baby with Apert syndrome. Northern International Medical College Journal Vol.11 (2) Jan 2020: 475-477

Synchronous Upper Intestinal Neurofibromas and Duodenal Periampullary Well-Differentiated Neuroendocrine Tumor Associated With Neurofibromatosis 1

2020 ◽  
pp. 000313482094523
Author(s):  
Jacob C. Balmer ◽  
Yana Mikhaylov ◽  
David N. Lewin ◽  
David M. Mahvi ◽  
E. Ramsay Camp
Keyword(s):  
Neuroendocrine Tumor ◽  
Malignant Tumors ◽  
Genetic Disorder ◽  
Gastrointestinal Symptoms ◽  
Pathological Examination ◽  
Type I ◽  
Nerve Sheath Tumor ◽  
Regional Lymph Nodes ◽  
Increased Risk ◽  
Well Differentiated

Neurofibromatosis type I (NF1) is an autosomal dominant genetic disorder associated with characteristic skin findings, as well as a fourfold increase in risk of malignancy. NF1 patient malignancies commonly include the central and peripheral nervous system, but these patients are also at high risk of developing gastrointestinal (GI) tumors. While most often these GI tumors are benign upper GI neurofibromas; clinicians should have a high suspicion for malignant tumors, degeneration into a malignant peripheral nerve sheath tumor or less common associated malignancies such as well-differentiated neuroendocrine tumor (formerly carcinoid tumor), when patients present with multiple GI tumors. Our patient underwent a Whipple for symptomatic neurofibromas associated with NF1 and was unexpectedly discovered to have a metastatic duodenal well-differentiated neuroendocrine tumor. The patient is a 66-year-old man with NF1 who presented with hematemesis and was found to have large gastric neurofibromas and an ampullary neurofibroma based on endoscopy and radiological imaging. Another ostensive neurofibroma was noted distally. A pancreatoduodenectomy was performed. Pathological examination identified the neurofibromas but the tumor measuring 1.4cm and arising from the minor duodenal papilla was, in fact, a synchronous well-differentiated neuroendocrine tumor metastatic to regional lymph nodes, consistent with pT2 pN1, Stage IIIB cancer. NF1 patients with multiple GI tumors are at an increased risk for malignancy. Therefore, a high index of suspicion for malignancy in any patient with NF1 presenting with gastrointestinal symptoms has implications for a surgeon, warranting not only a further diagnostic investigation, but also an appropriate surgical intervention and sampling for nodal spread. Because of the possibility of a simultaneous cancer, it is crucial to assess all suspicious tumors even if the masses appear endoscopically benign.

scholarly journals Effects of Transcranial Direct Current Stimulation (tDCS) on Go/NoGo Performance Using Food and Non-Food Stimuli in Patients with Prader–Willi Syndrome

2021 ◽  
Vol 11 (2) ◽  
pp. 250
Author(s):  
Albert B. Poje ◽  
Ann Manzardo ◽  
Kathleen M. Gustafson ◽  
Ke Liao ◽  
Laura E. Martin ◽  
...  
Keyword(s):  
Direct Current ◽  
Behavioral Problems ◽  
Transcranial Direct Current Stimulation ◽  
Genetic Disorder ◽  
Event Related Potentials ◽  
Prader Willi Syndrome ◽  
Feeding Difficulties ◽  
Direct Current Stimulation ◽  
Positive Effects ◽  
Related Potentials

Prader–Willi syndrome (PWS) is a neurodevelopmental genetic disorder characterized by multiple system involvement with hypotonia, poor suck with feeding difficulties, growth and other hormone deficiencies, intellectual disability, and behavioral problems with childhood onset of hyperphagia resulting in obesity, if not externally controlled. Transcranial direct current stimulation (tDCS) has been increasingly shown to modulate cognitive and behavioral processes in children and adults, including food-intake behaviors in patients with PWS. This study further reports the positive effects of brief tDCS sessions on Go/NoGo task performance involving food and non-food stimuli images, alterations in N2 brain amplitude, and genetic subgroup differences (maternal disomy 15, UPD; 15q11-q13 deletion, DEL) before and after tDCS as assessed by event-related potentials (ERPs) in 10 adults with PWS. The results indicate a group effect on baseline NoGo N2 amplitude in PWS patients with DEL vs UPD (p =0.046) and a decrease in NoGo N2 amplitude following tDCS (p = 0.031). Our tDCS approach also demonstrated a trend towards decreased response time. Collectively, these results replicate and expand prior work highlighting neurophysiological differences in patients with PWS according to genetic subtype and demonstrate the feasibility in examining neuromodulatory effects of tDCS on information processing in this patient population to stimulate additional research and treatment.

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.

scholarly journals A New Case of de novo Variant c.892C>T (p.Arg298Trp) in NACC1: A First Case Report From China

2021 ◽  
Vol 9 ◽  
Author(s):  
Baiyu Lyu ◽  
Yan Dong ◽  
Juan Kang
Keyword(s):  
Intellectual Disability ◽  
Congenital Cataract ◽  
De Novo ◽  
Neurodevelopmental Disorder ◽  
Brain Mri ◽  
Case Presentation ◽  
Feeding Difficulties ◽  
Severe Intellectual Disability ◽  
First Case ◽  
Infantile Epilepsy

Background: The nucleus accumbens associated 1 (NACC1) gene is a transcription factor member of the BTB/POZ family. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties.Case Presentation: We report a new case with a neurodevelopmental disorder characterized by severe intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. Brain MRI reveals brain dysplasia. We observe a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 gene in this case. Now, the child regularly goes to the hospital for rehabilitation training (once a month). Sodium Valproate (10 mg/kg/day) and Clobazam (10 mg/kg/day) are used in the treatment of epilepsy. A total of three articles were screened, and two papers were excluded. The search revealed one article related to a syndrome caused by a de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1; they screened the main clinical features of eight cases of a syndrome, which were summarized and analyzed.Conclusions: The NACC1 gene is a member of the BTB/POZ family of transcription factors. A de novo heterozygous c.892C>T (p.Arg298Trp) variant in the NACC1 may define a syndrome characterized by intellectual disability, infantile epilepsy, congenital cataract, and feeding difficulties. At present, there is no effective cure. In the future, we need more cases to determine the phenotype–genotype correlation of NACC1 variants. Many questions remain to be answered, and many challenges remain to be faced. Future transcriptional studies may further clarify this rare, recurrent variant, and could potentially lead to targeted therapies.

Prenatal diagnosis of oral-facial-digital type I syndrome in a fetus with partial monosomy of Xp22.2

2020 ◽  
pp. 55-57
Author(s):  
Л.И. Минайчева ◽  
Г.Н. Сеитова ◽  
М.О. Филиппова ◽  
А.А. Кашеварова ◽  
Н.А. Скрябин ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
De Novo ◽  
Ultrasound Examination ◽  
Type I ◽  
Prenatal Period ◽  
Second Trimester ◽  
Quantitative Real Time Pcr ◽  
Partial Monosomy ◽  
Molecular Cytogenetic ◽  
First Case

Представлен первый случай пренатальной диагностики оро-фацио-дигитального синдрома I типа (OMIM 311200) у плода с частичной моносомией Хр22.2. Причиной оро-фацио-дигитального синдрома I типа являются мутации в гене OFDI, случаи заболевания вследствие хромосомных микроделеций, затрагивающих ген OFDI встречаются редко. При ультразвуковом исследовании плода во втором триместре беременности выявлены врожденный порок развития головного мозга и множественные эхографические маркеры хромосомной и синдромальной патологии. Биологический образец плода (пуповинная кровь) получен в 21 неделю гестации посредством кордоцентеза. Молекулярно-цитогенетический анализ ДНК, выделенной из лимфоцитов пуповинной крови плода, с применением матричной сравнительной геномной гибридизации выявил частичную моносомию региона Хр22.2, размером 2,6 млн п.н.: arr[hg19] Xp22.2(11135472_13798048)×1. Наличие перестройки, а также ее de novo происхождение, подтверждено количественной ПЦР в режиме реального времени. The first case of prenatal diagnosis of type I oro-facio-digital syndrome (OMIM 311200) in fetus with partial monosomy Xp22.2 is presented. The cause of type I oro-facio-digital syndrome is mutations in the OFDI gene, cases of disease due to chromosomal microdeletions affecting the OFDI gene are rare. Ultrasound examination of the fetus in the second trimester of pregnancy revealed congenital defect of brain development and multiple echographic markers of chromosomal and syndrome pathology. An umbilical cord blood was obtained in 21 weeks of gestation by cordocentesis. aCGH revealed partial monosomy Xp22.2 at 2.6 Mb in size: arr [hg19] Xp22.2(11135472_13798048) × 1. The presence of microdeletion, as well as its de novo origin, was confirmed by the quantitative real time PCR. The use of high-resolution molecular cytogenetic analysis significantly expands the possibilities of syndrome monogenic pathology diagnosis in the prenatal period.

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