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Genes Mar 2024Noonan syndrome is a group of diseases with a similar clinical picture, consisting of 16 diseases caused by mutations in 15 genes. According to the literature,...
Noonan syndrome is a group of diseases with a similar clinical picture, consisting of 16 diseases caused by mutations in 15 genes. According to the literature, approximately half of all cases are attributed to Noonan syndrome type 1, NSML, caused by mutations in the gene. We analyzed 456 unrelated probands using a gene panel NGS, and in 206 cases, the cause of the disease was identified. Approximately half of the cases (107) were caused by variants in the gene, including three previously undescribed variants, one of which was classified as VOUS, and the other two as LP causative complex alleles. Frequent variants of the gene characteristics for Russian patients were identified, accounting for more than 38% (c.922A>G p.Asn308Asp, c.417G>C p.Glu139Asp, c.1403C>T p.Thr468Met) of all cases with mutations in the gene. A comparative characterization of frequent variants of the gene in different populations is shown. The most common features of Noonan syndrome in the studied sample were facial dysmorphisms and cardiovascular system abnormalities. A lower representation of patients with growth delay was observed compared to previously described samples.
Topics: Humans; Noonan Syndrome; Mutation; Alleles; Russia; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 38540404
DOI: 10.3390/genes15030345 -
Actas Dermo-sifiliograficas Apr 2024
Topics: Humans; LEOPARD Syndrome; Noonan Syndrome; Pigmentation Disorders; Mutation; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 38325537
DOI: 10.1016/j.ad.2022.05.049 -
Asian Journal of Surgery Apr 2024
Topics: Female; Humans; LEOPARD Syndrome; Fetus; Nervous System
PubMed: 38245422
DOI: 10.1016/j.asjsur.2024.01.017 -
Acta Dermato-venereologica Jan 2024
Topics: Humans; LEOPARD Syndrome; Melanoma; Mutation; Protein Tyrosine Phosphatase, Non-Receptor Type 11
PubMed: 38189222
DOI: 10.2340/actadv.v104.14720 -
Frontiers in Cardiovascular Medicine 2023Noonan syndrome with multiple lentigines (NSML, formerly known as LEOPARD syndrome) is a variant of Noonan syndrome which is an autosomal dominant disorder. Most cases...
Noonan syndrome with multiple lentigines (NSML, formerly known as LEOPARD syndrome) is a variant of Noonan syndrome which is an autosomal dominant disorder. Most cases of NSML are secondary to mutations of the protein-tyrosine phosphatase nonreceptor type 11 (). Hypertrophic cardiomyopathy (HCM) remains the most frequent and serious cardiac abnormality in this inherited syndrome, and it may lead to sudden cardiac death related to HCM-associated outflow obstruction and fatal arrhythmia. Beyond cardiac involvement, NSML may present with multiple lentigines, ocular hypertelorism, genital anomalies, short stature and deafness. Herein, we report three patients with NSML among three generations in one family, all presenting with multiple lentigines, HCM and other distinctive clinical and molecular features, including facial dysmorphism, deafness, family history of sudden death and mutations. This case series highlights the importance of early echocardiography examinations for patients with NSML. Careful family screening and genetic counselling are also necessary, especially in patients with diffuse lentigines or a history of sudden death among family members. We also discuss the distinctive cardiac features and phenotypic characteristics at different stages of NSML, including childhood, adulthood and elderhood.
PubMed: 37692036
DOI: 10.3389/fcvm.2023.1225667 -
Frontiers in Cardiovascular Medicine 2023As binary switches, RAS proteins switch to an ON/OFF state during signaling and are on a leash under normal conditions. However, in RAS-related diseases such as cancer... (Review)
Review
As binary switches, RAS proteins switch to an ON/OFF state during signaling and are on a leash under normal conditions. However, in RAS-related diseases such as cancer and RASopathies, mutations in the genes that regulate RAS signaling or the RAS itself permanently activate the RAS protein. The structural basis of this switch is well understood; however, the exact mechanisms by which RAS proteins are regulated are less clear. RAS/MAPK syndromes are multisystem developmental disorders caused by germline mutations in genes associated with the RAS/mitogen-activated protein kinase pathway, impacting 1 in 1,000-2,500 children. These include a variety of disorders such as Noonan syndrome (NS) and NS-related disorders (NSRD), such as cardio facio cutaneous (CFC) syndrome, Costello syndrome (CS), and NS with multiple lentigines (NSML, also known as LEOPARD syndrome). A frequent manifestation of cardiomyopathy (CM) and hypertrophic cardiomyopathy associated with RASopathies suggest that RASopathies could be a potential causative factor for CM. However, the current supporting evidence is sporadic and unclear. RASopathy-patients also display a broad spectrum of congenital heart disease (CHD). More than 15 genes encode components of the RAS/MAPK signaling pathway that are essential for the cell cycle and play regulatory roles in proliferation, differentiation, growth, and metabolism. These genes are linked to the molecular genetic pathogenesis of these syndromes. However, genetic heterogeneity for a given syndrome on the one hand and alleles for multiple syndromes on the other make classification difficult in diagnosing RAS/MAPK-related diseases. Although there is some genetic homogeneity in most RASopathies, several RASopathies are allelic diseases. This allelism points to the role of critical signaling nodes and sheds light on the overlap between these related syndromes. Even though considerable progress has been made in understanding the pathophysiology of RASopathy with the identification of causal mutations and the functional analysis of their pathophysiological consequences, there are still unidentified causal genes for many patients diagnosed with RASopathies.
PubMed: 37529712
DOI: 10.3389/fcvm.2023.1176828 -
Clinical Case Reports Jun 2023Noonan syndrome with multiple lentigines (NSML) is a rare RASopathy caused by pathogenic variants (PV) predominantly in gene. We report a 54-year-old male with apical...
Noonan syndrome with multiple lentigines (NSML) is a rare RASopathy caused by pathogenic variants (PV) predominantly in gene. We report a 54-year-old male with apical hypertrophic cardiomyopathy, who was diagnosed with NSML due to his short stature, multiple lentigines, winged neck, pectus excavatum, and a heterozygous PV in c.836A > ¡G.
PubMed: 37361648
DOI: 10.1002/ccr3.7607 -
Case Reports in Dermatological Medicine 2023LEOPARD syndrome (LS) is a rare autosomal dominant inherited or sporadic genetic disorder caused commonly by missense mutations in the protein-tyrosine...
LEOPARD syndrome (LS) is a rare autosomal dominant inherited or sporadic genetic disorder caused commonly by missense mutations in the protein-tyrosine phosphatase-nonreceptor type 11 () gene. Due to its rarity and a high chance of misdiagnosis, the epidemiological profile of LS is poorly established. To the best of our knowledge, this is the second report with a documented gene mutation in Saudi Arabia.
PubMed: 37260585
DOI: 10.1155/2023/4161574 -
International Medical Case Reports... 2023Lentigines are defined as multiple small pigmented macules measuring up to one centimeter and surrounded by normal-appearing skin, commonly caused by genetic factors....
Lentigines are defined as multiple small pigmented macules measuring up to one centimeter and surrounded by normal-appearing skin, commonly caused by genetic factors. LEOPARD syndrome (LS) is an autosomal dominant distinguished by the presence of several lentigines, with specific phenotypic characteristics that resembles Noonan syndrome (NS). LS is likely to be underdiagnosed or misdiagnosed because many of its symptoms are minor and the accurate diagnosis may be overlooked. Therapy for lentigines are generally aimed at tackling aesthetic disfigurement and its subsequent psychological impacts. This case report aims to highlight the efficacy of 532-nanometer (nm) Q-switched (QS) Nd:YAG laser in treating lentigines in a 21-year-old woman with LS overlap NS. The patient initially came to seek treatment of her facial lentigines. However, some mild abnormalities such as ocular hypertelorism, left eye ptosis, and webbed neck were observed. Hormonal, cardiac, and pulmonary functions were within normal limit. Histopathological results supported the diagnosis of lentigo. The patient was given sunscreen and depigmenting agents and was instructed to apply the medications routinely. The patient then underwent two sessions of 532-nm QS Nd:YAG laser with a 3 mm spot size, 1 J/cm fluence, and a 1 Hz frequency. Objective clinical improvements were observed using spectrophotometer examination, there were no side effects found, and she was satisfied with the results. Dermatologists should play an integral role in establishing the diagnosis and management of systemic syndrome, manifesting specifically as dermatological symptoms. Lentigines in LS last throughout the patient's lifespan. Nd:YAG laser therapy can be effective in treating lentigines with long-lasting results. It plays a role in improving the patient's life quality, especially where the genetic disorder itself is a debilitating condition. The limitation of this case report was the lack of a genetic test, as the suspected diagnosis was made based on clinical symptoms.
PubMed: 37193055
DOI: 10.2147/IMCRJ.S407416 -
Annals of Dermatology Apr 2023
PubMed: 37041714
DOI: 10.5021/ad.20.300