A First Case Report of Subependymoma in PTPN11 Mutation-Associated Noonan Syndrome.
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ABSTRACT:
SUBMITTER: Boonyawat B
PROVIDER: S-EPMC6766114 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
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A First Case Report of Subependymoma in <i>PTPN11</i> Mutation-Associated Noonan Syndrome.
Boonyawat Boonchai B Charoenpitakchai Mongkon M Suwanpakdee Piradee P
Case reports in neurological medicine 20190916
Noonan syndrome (NS) is an autosomal dominant disorder in some cases caused by <i>PTPN11</i> mutations. Since somatic mutations in <i>PTPN11</i> are seen in several tumor types, NS which causes germline <i>PTPN11</i> mutations are also increase the risk of hematologic malignancies and brain solid tumors. However, the report of brain tumors in Noonan syndrome remains rather rare. Here, we report the first case of an 11-year-old Thai boy with Noonan syndrome who presented with symptoms related to ...[more]
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Project description:ObjectiveTo analyze the clinical data and genetic characteristics of Noonan syndrome, both the effect and side effects of recombinant human growth hormone (rhGH) treatment.MethodsWe collected clinical data from 8 children with Noonan syndrome diagnosed from November 2017 to June 2021. The diagnosis was clarified by exome second-generation sequencing and parental PCR-NGS validation and interpretation of the preceding evidence, and growth hormone therapy was administered. Of the cases, four males and four females were seen for slow height growth and the median age at diagnosis was 8 years 7 months (1 year 7 months to 12 years 6 months).ResultsHere, 7 children were treated with rhGH. Compared to the pre-treatment period, the growth rate increased after rhGH treatment [3.7 ± 0.5 cm/year before treatment and 8.0 ± 1.0 cm/year after treatment, p < 0.01], with the maximum growth rate between 3 and 6 months of treatment and decreasing with the duration of treatment thereafter. The growth hormone treatment was discontinued and the orthopedic consultation was ordered with regular follow-up, which was considered to be related to the PTPN11 mutation.ConclusionNoonan syndrome is characterized by slow growth, short stature, mental retardation, peculiar facial features, structural heart abnormalities and abnormal bone metabolism. and osteochondroma was found after case 2 rhGH treatment. Genetic examination is mostly caused by PTPN11 mutation. It is recommended to pay attention to bone metabolism abnormalities before growth hormone treatment, especially in children with PTPN11 mutations.
| S-EPMC10655517 | biostudies-literature
Project description:Noonan syndrome (NS) is characterized by short stature, facial dysmorphisms and congenital heart defects. PTPN11 mutations are the most common cause of NS. Patients with NS have a predisposition for leukemia and certain solid tumors. Data on the incidence of malignancies in NS are lacking. Our objective was to estimate the cancer risk and spectrum in patients with NS carrying a PTPN11 mutation. In addition, we have investigated whether specific PTPN11 mutations result in an increased malignancy risk. We have performed a cohort study among 297 Dutch NS patients with a PTPN11 mutation (mean age 18 years). The cancer histories were collected from the referral forms for DNA diagnostics, and by consulting the Dutch national registry of pathology and the Netherlands Cancer Registry. The reported frequencies of cancer among NS patients were compared with the expected frequencies using population-based incidence rates. In total, 12 patients with NS developed a malignancy, providing a cumulative risk for developing cancer of 23% (95% confidence interval (CI), 8-38%) up to age 55 years, which represents a 3.5-fold (95% CI, 2.0-5.9) increased risk compared with that in the general population. Hematological malignancies occurred most frequently. Two malignancies, not previously observed in NS, were found: a malignant mastocytosis and malignant epithelioid angiosarcoma. No correlation was found between specific PTPN11 mutations and cancer occurrence. In conclusion, this study provides first evidence of an increased risk of cancer in patients with NS and a PTPN11 mutation, compared with that in the general population. Our data do not warrant specific cancer surveillance.
| S-EPMC3172922 | biostudies-literature
Project description:BackgroundNoonan syndrome is an autosomal dominant, variably expressed multisystem disorder characterized by specific facial and cardiac defects, delayed growth, ectodermal abnormalities, and lymphatic dysplasias. Lymphedema and chylous pleural effusions are common in Noonan syndrome, but protein-losing enteropathy (PLE) has only rarely been described in the condition and little is known about its genetic associations.Case presentationWe report the case of a 30-year-old Chinese woman who developed severe recurrent edema and hypoproteinemia. Gastroduodenoscopy showed a "snowflake" appearance of lymphangiectasia in the duodenum, and CT reconstruction of the small intestine showed segmental thickening of the intestinal wall with localized stenosis. Whole exome sequencing revealed that the patient harbored a pathogenic variant of PTPN11 (c.A922G p.N308D), which was unfortunately inherited by her 2.5-year-old daughter who had short stature and atrial septal defect but no hypoproteinemia.ConclusionsThis case of Noonan syndrome with PLE was associated with a PTPN11 mutation. A comprehensive review of PLE in Noonan syndrome revealed that PLE often presents late in this context but there is no clear genotype-phenotype correlation. Genetic evaluation with next-generation sequencing can be useful for securing the diagnosis and planning early intervention and management.
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Project description:Recent advances in molecular and genetic approaches have identified a number of genes responsible for Noonan syndrome (NS). However, there has been limited analysis of the genotype-phenotype correlation of NS patients. Here, we report the case of a Japanese patient with NS possessing a c.853T>C (p.Phe285Leu) mutation in the gene encoding protein-tyrosine phosphatase, nonreceptor-type 11 (PTPN11). To clarify genotype-phenotype correlations, the accumulation of data on the clinical course of patients with genetically confirmed NS is important. We summarized the cases with mutations at PTPN11 position 285 and found that c854T>C (p.Phe285Ser) is the most common mutation at this position. In these reports, although little is mentioned about the genotype-phenotype correlation, two patients with NS possessing the PTPN11 c854T>C (p.Phe285Ser) mutation accompanied by chylothorax are described. There is still a lack of detailed information about the phenotype associated with the c.853T>C (p.Phe285Leu) mutation observed in this case. More research is needed to better understand these cases.
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Project description:IntroductionMutations in PTPN11 are associated with Noonan syndrome (NS). Although the effectiveness of growth hormone therapy (GHT) in treating short stature due to NS has been previously demonstrated, the effect of PTPN11 mutation status on the long-term outcomes of GHT remains to be elucidated.MethodsThis analysis included pooled data from the observational American Norditropin Studies: Web-Enabled Research Program (NCT01009905) and the randomized, double-blinded GHLIQUID-4020 clinical trial (NCT01927861). Pediatric patients with clinically diagnosed NS and confirmed PTPN11mutation status were eligible for inclusion. The effectiveness analysis included patients who were GHT-naïve and pre-pubertal at GHT start. Growth outcomes and safety were assessed over 4 years of GHT (Norditropin®, Novo Nordisk A/S).ResultsA total of 69 patients were included in the effectiveness analysis (71% PTPN11 positive). The proportion of females was 32.7 and 30.0% in PTPN11-positive and negative patients, respectively, and mean age at GHT start was 6.4 years in both groups. Using general population reference data, after 4 years of GHT, the mean (s.d.) height SD score (HSDS) was -1.9 (1.1) and -1.7 (0.8) for PTPN11-positive and PTPN11-negative patients, respectively, with no statistical difference observed between groups. The mean (s.d.) change in HSDS at 4 years was +1.3 (0.8) in PTPN11-positive patients and +1.5 (0.7) in PTPN11-negative patients (no significant differences between groups). Safety findings were consistent with previous analyses.ConclusionsGHT resulted in improved growth outcomes over 4 years in GHT-naïve, pre-pubertal NS patients, irrespective of PTPN11 mutation status.
| S-EPMC9066595 | biostudies-literature
Project description:ObjectiveNoonan syndrome (NS), an autosomal dominant disease known as a RASopathy, is caused by germline mutations in mitogen-activated protein kinase pathway genes. A RIT1 gene mutation has been found to cause NS. The present study summarizes RIT1 gene mutation sites and associated clinical phenotypes.MethodsWe retrospectively analyzed the clinical characteristics of a case of NS caused by RIT1 mutation in our hospital, and searched the PubMed database, China National Knowledge Infrastructure (CNKI) database and Wanfang database with the keywords Noonan syndrome and RIT1. Studies published between May 1, 2014 and July 1, 2021 were retrieved. By reviewing the abstracts and full text of the studies, we screened NS cases associated with RIT1 mutation in children 0-18 years of age. The clinical characteristics of these cases were summarized.ResultsA total of 41 cases were analyzed, including 13 boys and 28 girls. There were 14 premature cases. The age at diagnosis was 4 days to 18 years, and 10 cases were diagnosed at 0-1 years of age. Common amino acid substitution positions included 57 (13/41), 95 (7/41), 82 (8/41), and 90 (4/41). A total of 63.63% cases had abnormal prenatal examination results, manifesting mainly as fetal neck edema, polyhydramnios and cardiac malformation. With respect to abnormal conditions after birth, 70-80% of patients had typical developmental malformations of the face, neck and thorax; 19/35 patients had abnormal lymphatic development; and a portion of patients had short stature and motor development disorders. A total of 87.80% (36/41) patients had cardiac dysplasia, among which hypertrophic cardiomyopathy (HCM) accounted for 58.53%. A total of 84.62% of patients carrying the p.A57G mutation had HCM, but no HCM was found in patients with the p.G95A mutation. A total of 34.15% of patients had pulmonary artery or pulmonary valve stenosis (PVS). In patients with the p.M90I mutation, 75% had PVS. Patients with concurrent HCM and PVS accounted for 19.51 and 48.78% of patients had supraventricular tachycardia.ConclusionA RIT1 gene mutation causing NS was associated with a high rate of abnormal prenatal examination findings. Most patients had typical NS craniofacial deformities, and some have short stature and motor development disorders. The cardiac deformity rate was high, and HCM was common. Some patients had supraventricular arrhythmias. Heart abnormalities showed high heterogeneity, given the various mutation loci.
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Project description: Not available
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Project description:Neurofibromatosis-Noonan syndrome is a rare RASopathy syndrome. It occurs due to the mutation in the NF1 gene and the patients present with the phenotypic features of both Neurofibromatosis and Noonan syndrome. Here a case of an early adolescent girl is described who presented with the chief complaint of primary amenorrhoea and on evaluation was diagnosed to be a patient of Neurofibromatosis-Noonan syndrome. The index case was short-statured with a short and broad neck. Physical examination revealed a pointed pinna, hypertelorism, telecanthus, characteristic facies, and multiple freckles all over the body. She also had numerous atypical café-au-lait spots. Whole genome sequencing revealed Neurofibromatosis-Noonan syndrome which was likely a pathogenic variant causative of the typical phenotype present with a mutation in the neurofibromin gene (NF1) on chromosome 17q11. We discuss here the management and follow-up of the case.
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