RESUMEN

BACKGROUND/OBJECTIVE: Laser therapy has emerged as a widely favored treatment option for solar lentigines (SL). However, a significant challenge associated with this treatment, particularly among individuals with darker skin tones, is the notable risk of postinflammatory hyperpigmentation (PIH) induction. In response to these concerns, the authors conducted a prospective, self-controlled study to comprehensively evaluate the safety and effectiveness of 532-nm picosecond laser, both with and without a microlens array (MLA), for the management of SL in patients with Fitzpatrick skin types (FST) III-V. METHODS: Twenty-seven patients with FST III-V and bilateral SL on the face underwent randomized treatment. One side of the face was treated with a 532-nm picosecond laser coupled with an MLA, utilizing the fractional pigment toning (FPT) technique, while the other side received treatment without the MLA, following the conventional technique (CT). The FPT technique utilized a 9-mm spot size with a fluence of 0.47 J/cm2 for two passes covering 40% of the area. In contrast, the CT used a 4.5-mm handpiece with fluence ranging from 0.3 to 0.7 J/cm2. Patients received a single treatment and were evaluated for pigment clearance, occurrence of PIH, and other adverse effects at 2 weeks, 1, 3, and 6 months posttreatment. RESULTS: Twenty-seven participants completed the study protocol. Analysis of pigment clearance, measured via 3D photography, showed significant improvement from 2 weeks to 6 months posttreatment for both the FPT technique (p < 0.001) and CT (p = 0.004). PIH occurred in 64%, 80%, 96%, and 88% of cases on the CT side, compared to 8%, 32%, 36%, and 16% on the FPT technique side at 2 weeks, 1, 3, and 6 months posttreatment, respectively. The incidence of PIH was significantly lower on the FPT technique side compared to the CT side throughout the follow-up periods. Additionally, transient and mild hypopigmentation occurred in one participant (4%) on the FPT technique side and in five participants (20%) on the CT side. No other adverse effects were observed during the study. CONCLUSIONS: The 532-nm picosecond laser emerges as a safe and efficacious treatment modality for SL in individuals with FST III-V. Particularly noteworthy is the efficacy of the FPT technique, which demonstrates comparable effectiveness while significantly reducing the incidence of PIH compared to the CT.

Asunto(s)

Láseres de Estado Sólido , Lentigo , Humanos , Estudios Prospectivos , Femenino , Adulto , Masculino , Persona de Mediana Edad , Lentigo/terapia , Láseres de Estado Sólido/uso terapéutico , Pueblo Asiatico , Terapia por Luz de Baja Intensidad/métodos , Resultado del Tratamiento , Hiperpigmentación/etiología , Pigmentación de la Piel

RESUMEN

A better understanding of human melanocyte (MC) and MC stem cell biology is essential for treating MC-related diseases. This study employed an inherited pigmentation disorder carrying the SASH1S519N variant in a Hispanic family to investigate SASH1 function in the MC lineage and the underlying mechanism for this disorder. We used a multidisciplinary approach, including clinical examinations, human cell assays, yeast 2-hybrid screening, and biochemical techniques. Results linked early hair graying to the SASH1S519N variant, a previously unrecognized clinical phenotype in hyperpigmentation disorders. In vitro, we identified SASH1 as a regulator in MC stem cell maintenance and discovered that TNKS2 is crucial for SASH1's role. In addition, the S519N variant is located in one of multiple tankyrase-binding motifs and alters the binding kinetics and affinity of the interaction. In summary, this disorder links both gain and loss of pigmentation in the same individual, hinting to accelerated aging in human MC stem cells. The findings offer insights into the roles of SASH1 and TNKS2 in MC stem cell maintenance and the molecular mechanisms of pigmentation disorders. We propose that a comprehensive clinical evaluation of patients with MC-related disorders should include an assessment and history of hair pigmentation loss.

RESUMEN

OBJECTIVES: Freckles and lentigines are common pigmented problems which not only cause substantial cosmetic morbidity but also create psychosocial concern. The available modalities for the treatment of pigmented lesions are often unsatisfactory for patients, require a long treatment period, and often cause skin irritation. With the advent of lasers, safe and effective treatment options for epidermal pigmentation have become more varied for different Fitzpatrick skin types. We aimed to evaluate the efficacy and safety of 577-nm yellow laser in the treatment of pigmented epidermal lesions. METHODS: This study was carried out on 50 patients presented with pigmented epidermal lesions (25 presented with freckles and 25 presented with lentigines). Each patient received four treatment sessions with a 577-nm diode laser at 2-week intervals. RESULTS: There was significant improvement in freckles and lentigines, as 23 out of 50 patients showed marked improvement, 11 patients showed moderate improvement, 10 patients showed mild improvement, and only six patients had no changes. Moreover, 23 patients were very satisfied, 18 patients were satisfied, and nine patients were not satisfied. As regards the safety of the 577-nm yellow laser, there was no significant adverse effect among patients except pain, erythema, and hyperpigmentation, which resolved within one month after treatment. CONCLUSIONS: This study showed that the 577-nm yellow laser is an effective, safe, and well-tolerated device in the treatment of freckles and lentigines.

Asunto(s)

Láseres de Semiconductores , Lentigo , Humanos , Femenino , Adulto , Masculino , Persona de Mediana Edad , Láseres de Semiconductores/uso terapéutico , Adulto Joven , Lentigo/cirugía , Resultado del Tratamiento , Adolescente , Melanosis/radioterapia , Satisfacción del Paciente , Terapia por Luz de Baja Intensidad/métodos

RESUMEN

Cytoplasmic protein tyrosine phosphatase nonreceptor type 11 (PTPN11) and Drosophila homolog Corkscrew (Csw) regulate the mitogen-activated protein kinase (MAPK) pathway via a conserved autoinhibitory mechanism. Disease-causing loss-of-function (LoF) and gain-of-function (GoF) mutations both disrupt this autoinhibition to potentiate MAPK signaling. At the Drosophila neuromuscular junction glutamatergic synapse, LoF/GoF mutations elevate transmission strength and reduce activity-dependent synaptic depression. In both sexes of LoF/GoF mutations, the synaptic vesicles (SV)-colocalized synapsin phosphoprotein tether is highly elevated at rest, but quickly reduced with stimulation, suggesting a larger SV reserve pool with greatly heightened activity-dependent recruitment. Transmission electron microscopy of mutants reveals an elevated number of SVs clustered at the presynaptic active zones, suggesting that the increased vesicle availability is causative for the elevated neurotransmission. Direct neuron-targeted extracellular signal-regulated kinase (ERK) GoF phenocopies both increased local presynaptic MAPK/ERK signaling and synaptic transmission strength in mutants, confirming the presynaptic regulatory mechanism. Synapsin loss blocks this elevation in both presynaptic PTPN11 and ERK mutants. However, csw null mutants cannot be rescued by wild-type Csw in neurons: neurotransmission is only rescued by expressing Csw in both neurons and glia simultaneously. Nevertheless, targeted LoF/GoF mutations in either neurons or glia alone recapitulate the elevated neurotransmission. Thus, PTPN11/Csw mutations in either cell type are sufficient to upregulate presynaptic function, but a dual requirement in neurons and glia is necessary for neurotransmission. Taken together, we conclude that PTPN11/Csw acts in both neurons and glia, with LoF and GoF similarly upregulating MAPK/ERK signaling to enhance presynaptic Synapsin-mediated SV trafficking.

Asunto(s)

Proteínas de Drosophila , Sistema de Señalización de MAP Quinasas , Neuroglía , Neuronas , Terminales Presinápticos , Proteína Tirosina Fosfatasa no Receptora Tipo 11 , Sinapsinas , Transmisión Sináptica , Vesículas Sinápticas , Animales , Femenino , Masculino , Animales Modificados Genéticamente , Drosophila , Proteínas de Drosophila/metabolismo , Proteínas de Drosophila/genética , Sistema de Señalización de MAP Quinasas/fisiología , Mutación , Neuroglía/metabolismo , Neuroglía/fisiología , Unión Neuromuscular/metabolismo , Unión Neuromuscular/fisiología , Neuronas/metabolismo , Neuronas/fisiología , Terminales Presinápticos/metabolismo , Terminales Presinápticos/fisiología , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Sinapsinas/metabolismo , Sinapsinas/genética , Transmisión Sináptica/fisiología , Vesículas Sinápticas/metabolismo

RESUMEN

Background: Solar lentigines are common hyperpigmented lesions typically appearing after 50 years of age and associated with negative psychological effects in affected individuals. Topical depigmenting products, such as hydroquinone and even the Kligman's formula, are usually ineffective for treating lentigines. Stabilized cysteamine has been recently shown to be as effective as the modified Kligman's formula for treating melasma. In this study, we evaluated the therapeutic effect of a stabilized cysteamine on solar lentigines. Methods: A vehicle-controlled, double-blind, and randomized study was performed on 30 patients with solar lentigines. Stabilized cysteamine or vehicle control creams were applied on solar lentigines on the dorsum of the hands daily for 12 weeks. Clinical measurements with colorimetry and visual analog scale were performed at baseline, 4, 8, and 12 weeks. Results: Statistically significant results were obtained in the cysteamine group versus the vehicle control group. Stabilized cysteamine provided a 40% reduction in colorimetric values (p < 0.002) versus a 2% reduction in the vehicle group (p < 0.405). Cysteamine also provided a 40% reduction in VAS (p < 0.001) versus a 2% reduction in the vehicle group (p < 0.245). Conclusion: Significant improvement of solar lentigines was observed after 12 weeks of application of stabilized cysteamine by all evaluation methods. Stabilized cysteamine represents a highly effective topical treatment for solar lentigines and can be considered as one of the first topical therapies effective on this hyperpigmentary disorder.

RESUMEN

Background: Solar lentigines (SLs), serving as a prevalent characteristic of skin photoaging, present as cutaneous aberrant pigmentation. However, the underlying pathogenesis remains unclear and there is a dearth of reliable diagnostic biomarkers. Objective: The aim of this study was to identify diagnostic biomarkers for SLs and reveal its immunological features. Methods: In this study, gene expression profiling datasets (GSE192564 and GSE192565) of SLs were obtained from the GEO database. The GSE192564 was used as the training group for screening of differentially expressed genes (DEGs) and subsequent depth analysis. Gene set enrichment analysis (GSEA) was employed to explore the biological states associated with SLs. The weighted gene co-expression network analysis (WGCNA) was employed to identify the significant modules and hub genes. Then, the feature genes were further screened by the overlapping of hub genes and up-regulated differential genes. Subsequently, an artificial neural network was constructed for identifying SLs samples. The GSE192565 was used as the test group for validation of feature genes expression level and the model's classification performance. Furthermore, we conducted immune cell infiltration analysis to reveal the immune infiltration landscape of SLs. Results: The 9 feature genes were identified as diagnostic biomarkers for SLs in this study. And an artificial neural network based on diagnostic biomarkers was successfully constructed for identification of SLs. GSEA highlighted potential role of immune system in pathogenesis of SLs. SLs samples had a higher proportion of several immune cells, including activated CD8 T cell, dendritic cell, myeloid-derived suppressor cell and so on. And diagnostic biomarkers exhibited a strong relationship with the infiltration of most immune cells. Conclusion: Our study identified diagnostic biomarkers for SLs and explored its immunological features, enhancing the comprehension of its pathogenesis.

RESUMEN

Purpose: Post-inflammatory hyperpigmentation (PIH) and solar lentigines are dark spots of skin from excessive melanin production due to injury or UV exposure. This 12-week single-center study assessed the efficacy and tolerability of a novel targeted pigment-correcting spot treatment gel suspension cream (Dark Spot Treatment) for improving mild-to-moderate PIH or solar lentigines. Patients and Methods: Female participants (N = 41) aged 25-65 with mild-to-moderate facial dark spots applied Dark Spot Treatment daily for 12 weeks. Investigators assessed overall hyperpigmentation, skin tone evenness, and dark spot intensity, contrast, and size at Weeks 2, 4, 8, and 12. Participant self-assessments occurred at Weeks 1, 2, 4, 8, and 12. Tolerability was assessed by clinical grading and participant reporting. Results: Dark Spot Treatment improved overall hyperpigmentation, skin tone evenness, and dark spot intensity and contrast at Weeks 2 through 12, and dark spot size at Weeks 4 through 12 (all p < 0.001 compared to baseline). Participant self-assessments showed high overall satisfaction. Dark Spot Treatment was well tolerated. Conclusion: The novel pigment-correcting Dark Spot Treatment significantly improved the appearance of PIH and solar lentigines, had high participant satisfaction, and was well tolerated.

RESUMEN

The appearance of actinic lentigines mainly found on face, back of the hands, upper back and décolleté is associated with chronic sun exposure. However, there is no study looking at the role of long UVA specifically in the development of actinic lentigines. This study was conducted in 20 Japanese adult women exposed on the upper back area three times per week for 6 weeks to incremental sub-erythemal UVA1 doses (5 J/cm2 at weeks 1 and 2, 10 J/cm2 at weeks 3 and 4 and 15 J/cm2 at weeks 5 and 6). Clinical assessment, performed on day 0 (before any exposure), and on days 14, 28 and 42, included the evaluation of skin pigmentation (pigmented spots), chromametry of the pigmented skin lesions and measurement of dyschromy. The number of pigmented spots and uniformity of the skin's pigmentation were clearly increased in comparison with baseline, statistical significance of the difference (p < 0.05) being reached at D 28 and D 42 in both cases. In conclusion, repeated sub-erythemal UVA1 exposure induces the development of actinic lentigines. Thus, a suitable protection including long UVA coverage is also needed to prevent from the damages induced by low, sub-erythemal doses of UV exposure.

Asunto(s)

Lentigo , Trastornos por Fotosensibilidad , Trastornos de la Pigmentación , Adulto , Humanos , Femenino , Rayos Ultravioleta/efectos adversos , Piel , Eritema/etiología , Lentigo/etiología

RESUMEN

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 (PTPN11). 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 PTPN11 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.

Asunto(s)

Láseres de Estado Sólido , Lentigo , Humanos , Lentigo/terapia , Rayos Láser , Láseres de Estado Sólido/uso terapéutico

Asunto(s)

Cardiomiopatía Hipertrófica , Síndrome LEOPARD , Síndrome de Noonan , Humanos , Síndrome LEOPARD/complicaciones , Síndrome LEOPARD/diagnóstico , Síndrome LEOPARD/genética , Síndrome de Noonan/complicaciones , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética , Mutación , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Fenotipo , Genotipo , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética

RESUMEN

Noonan syndrome with multiple lentigines (NSML) is a rare RASopathy caused by pathogenic variants (PV) predominantly in PTPN11 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 PTPN11 c.836A > ¡G.

RESUMEN

BACKGROUND: Vitamin C is a micronutrient present in high concentrations in normal skin and a highly prescribed cosmeceutical, well known for protecting against ultraviolet-induced pigmentation and regulating collagen production. However, there is a lack of studies evaluating the efficacy of topical vitamin C in photoaging and melasma, with this systematic review being the first to assess the existing evidence. AIM: This systematic review aims to assess whether topical vitamin C could be effective in reversing photoaging signs and treating melasma. METHODS: Prospective, randomized controlled trials assessing protocols with topically applied vitamin C in patients with melasma or photodamage were searched in Medline, CENTRAL, and Scopus databases until the 12th of May 2022. Risk of bias was conducted in accordance with Cochrane Collaboration's tool for assessing the risk of bias in randomized trials, using RevMan 5.0. RESULTS: Seven publications were included, with 139 volunteers in total. Studies that evaluated the topography of skin indicated that the treated skin appeared smoother and less wrinkled, which was supported by biopsies data. On objective assessments of pigmentation, there was a significant lightening of the skin treated. Hydration improved equally in the vitamin C and placebo-treated sites. CONCLUSIONS: This study revealed that vitamin C is effective in treating uneven, wrinkled skin and has depigmenting properties, but long-term use may be needed to achieve noticeable changes. Q-switched Nd:YAG laser-associated protocols appear beneficial in enhancing vitamin C effects. Topical vitamin C may be a suitable alternative for melasma and photoaging, but more studies are needed to confirm these results and assess the ideal vitamin C concentration.

Asunto(s)

Láseres de Estado Sólido , Melanosis , Envejecimiento de la Piel , Humanos , Ácido Ascórbico , Estudios Prospectivos , Melanosis/terapia , Piel/patología , Vitaminas , Resultado del Tratamiento

RESUMEN

BACKGROUND: We aimed to examine clinical features and outcomes of consecutive molecularly characterized patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy. METHODS: A retrospective, longitudinal multicenter cohort of consecutive children and adults with a genetic diagnosis of Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy between 2002 and 2019 was assembled. We defined a priori 3 different patterns of left ventricular remodeling during follow-up: (1) an increase in ≥15% of the maximal left ventricular wall thickness (MLVWT), both in mm and z-score (progression); (2) a reduction ≥15% of the MLVWT, both in mm and z-score (absolute regression); (3) a reduction ≥15% of the MLVWT z-score with a stable MLVWT in mm (relative regression). The primary study end point was a composite of cardiovascular death, heart transplantation, and appropriate implantable cardioverter defibrillator-shock. RESULTS: The cohort comprised 42 patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy, with a median age at diagnosis of 3.5 (interquartile range, 0.2-12.3) years. Freedom from primary end point was 92.7% (95% CI, 84.7%-100%) 1 year after presentation and 80.9% (95% CI, 70.1%-90.7%) at 5 years. Patients with MLVWT z-score >13.7 showed reduced survival compared with those with <13.7. During a median follow-up of 3.7 years (interquartile range, 2.6-7.9), absolute regression was the most common type of left ventricular remodeling (n=9, 31%), followed by progression (n=6, 21%), and relative regression (n=6, 21%). CONCLUSIONS: These findings provide insights into the natural history of left ventricular hypertrophy, and can help inform clinicians regarding risk stratification and clinical outcomes in patients with Noonan syndrome with multiple lentigines and hypertrophic cardiomyopathy.

Asunto(s)

Cardiomiopatía Hipertrófica , Síndrome LEOPARD , Síndrome de Noonan , Niño , Adulto , Humanos , Lactante , Preescolar , Síndrome LEOPARD/diagnóstico , Síndrome LEOPARD/genética , Estudios Retrospectivos , Remodelación Ventricular , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Síndrome de Noonan/diagnóstico , Síndrome de Noonan/genética

RESUMEN

Lentigines are well-defined, small, brown macules resulting from the accumulation of melanin content in the basement membrane zone with an increase in the number of melanocytes. Hereditary multiple lentigines (ML) can be associated with multiple genes and are not commonly encountered in clinical practice. Patients can solely have skin involvement or present with multisystemic deformative phenotypes. This study aimed to describe four unrelated Chinese families presenting with ML as their first visit symptom. We performed whole-exome sequencing (WES) and Sanger sequencing on all patients and immediate family members for precise molecular diagnosis. Two novel variants c.1548 T > A (p.Ser516Arg) and c.1811C > A (p.Thr604Lys) in SASH1, and two recurrent variants c.1403C > T (p.Thr468Met) and c.1493G > T (p.Arg498Leu) in PTPN11, were identified in these four families. We also summarized the genes associated with ML and differential diagnosis of pigment abnormality. We suggested that the molecular diagnosis of ML should be emphasized because it can help in the clinical differential diagnosis and further genetic counseling and prognosis.

Asunto(s)

Pueblos del Este de Asia , Lentigo , Humanos , Lentigo/diagnóstico , Lentigo/genética , Melanocitos , Mutación , Fenotipo , Síndrome

RESUMEN

BACKGROUND: During aging, human skin is facing hyperpigmentation disorders: senile lentigo (chronobiologic aging) leads to loss of melanogenesis' control while solar lentigo (UV exposure) promotes an increase of oxidized proteins, melanogenesis, and lipofuscin. AIMS: Stromal-cell-derived-factor-1 (SDF-1) was identified as key regulator of hyperpigmentation and its expression is reduced in senescent fibroblasts, highlighting this protein as new target for skin hyperpigmentation. MATERIALS: We developed two skin explant models mimicking of senile and solar lentigo, based on H2 O2 systemic treatment and UV irradiation, respectively. We evaluated Himanthalia elongata extract (HEX) on these models after 5 days of treatment and analyzed SDF-1 expression and skin pigmentation. For solar lentigo, we also analyzed oxidized proteins and lipofuscin accumulation. Finally, we evaluated HEX in vivo on nearly 100 multi ethnicities' volunteers. RESULTS: SDF-1 expression decreased in senile lentigo model, associated with hyperpigmentation. HEX application restored SDF-1 expression, leading to skin pigmentation decrease. For solar lentigo, we showed an impact of UVs on SDF-1 expression linked to hyperpigmentation, while the application of HEX restored SDF-1 expression and reduced skin pigmentation. On same model, HEX reduced oxidized proteins quantity and lipofuscin which increased after UV exposure. Clinically, HEX reduced dark spot pigmentation on Caucasian volunteers' hands and on Asian and African volunteers' face after 28 days. DISCUSSION: We have developed ex vivo models mimetic of senile and solar lentigo and showed for a very first time that SDF-1 can be also a key regulator for UV-induced hyperpigmentation. CONCLUSION: Our ex vivo and clinical studies highlighted the power of HEX with strong reduction of dark spots regardless of volunteers' ethnicities.

Asunto(s)

Hiperpigmentación , Lentigo , Humanos , Lipofuscina , Hiperpigmentación/tratamiento farmacológico , Piel/metabolismo , Lentigo/tratamiento farmacológico , Envejecimiento

RESUMEN

RASopathies comprise a group of clinically overlapping developmental disorders caused by genetic variations affecting components or modulators of the RAS-MAPK signaling cascade, which lead to dysregulation of signal flow through this pathway. Noonan syndrome and the less frequent, clinically related disorders, Costello syndrome, cardiofaciocutaneous syndrome, Noonan syndrome with multiple lentigines, and Noonan syndrome-like disorder with loose anagen hair are part of the RASopathy spectrum and share a recognizable pattern of multisystem involvement. This review describes the "Noonan syndrome-like" phenotype as a common phenotypic signature of generalized developmental RAS pathway dysregulation. Distinctive features of the different entities are revisited against the background of the understanding of underlying genetic alterations and genotype correlations, which has evolved rapidly during the past 20 years, thereby leading to suggestions regarding the nosology of RASopathies.

Asunto(s)

Síndrome de Costello , Cardiopatías Congénitas , Síndrome de Noonan , Humanos , Síndrome de Noonan/genética , Cardiopatías Congénitas/genética , Síndrome de Costello/genética , Insuficiencia de Crecimiento/genética , Mutación

RESUMEN

The cardiovascular phenotype associated with RASopathies has expanded far beyond the original descriptions of pulmonary valve stenosis by Dr Jaqueline Noonan in 1968 and hypertrophic cardiomyopathy by Hirsch et al. in 1975. Because of the common underlying RAS/MAPK pathway dysregulation, RASopathy syndromes usually present with a typical spectrum of overlapping cardiovascular anomalies, although less common cardiac defects can occur. The identification of the causative genetic variants has enabled the recognition of specific correlations between genotype and cardiac phenotype. Characterization and understanding of genotype-phenotype associations is not only important for counseling a family of an infant with a new diagnosis of a RASopathy condition but is also critical for their clinical prognosis with respect to cardiac disease, neurodevelopment and other organ system involvement over the lifetime of the patient. This review will focus on the cardiac manifestations of the most common RASopathy syndromes, the relationship between cardiac defects and causal genetic variation, the contribution of cardiovascular abnormalities to morbidity and mortality and the most relevant follow-up issues for patients affected by RAS/MAPK pathway diseases, with respect to cardiac clinical outcomes and management, in children and in the adult population.

Asunto(s)

Displasia Ectodérmica , Cardiopatías Congénitas , Síndrome de Noonan , Humanos , Síndrome de Noonan/genética , Síndrome de Noonan/diagnóstico , Cardiopatías Congénitas/genética , Cardiopatías Congénitas/diagnóstico , Insuficiencia de Crecimiento/genética , Insuficiencia de Crecimiento/diagnóstico , Proteínas ras/genética , Displasia Ectodérmica/genética , Mutación