Introduction:
Genes are the prime controlling factor that holds the responsibility for the proper structure and functioning of the human body, even at the basic cellular level. Any form of deviations or aberrations in the genes, even minute and microscopic, reflects in the form of complex defects. Noonan Syndrome with multiple lentigines is one such inborn defect that typically affects the facial form and structure of a person.
What Is Noonan Syndrome With Multiple Lentigines?
Noonan Syndrome with Multiple Lentigines (NSML) is an exceptionally rare condition that gives rise to remarkable defects in various organs in the body. Multiple lentigines syndrome and Leopard syndrome are some of the widely used synonyms for NSML. The skin develops highly pigmented spots over the body surfaces that are medically known by the name lentigines. Lentigines are routinely dark brown, however, other specific skin pigmentations may also arise concurrently.
What Are the Causes of Noonan Syndrome With Multiple Lentigines?
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NSML is an inborn condition that arises from irregularities and aberrations in certain genes. Undesirable and unexpected deviations in the gene pattern are technically known by the term mutations.
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NSML is seen in association with changes in certain genes. A highly significant proportion of the NSML patients displayed aberrations in the gene PTPN11 (protein-tyrosine phosphatase, nonreceptor type 11).
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However, this syndrome is occasionally found in individuals who exhibit aberrations in certain other genes like BRAF, RAF1, and MAP2K1 (Mitogen-activated protein kinase kinase1). Alterations in any of these genes reflect in the form of cellular disruptions particularly affecting the division and maturation of the cells.
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The majority of these alterations develop from familial influences and exhibit an autosomal dominant pattern of inheritance. As a result, the condition gets expressed and manifested in the next generation, even if only one parent is affected by NSML.
What Are the Symptoms Associated With Noonan Syndrome of Multiple Lentigines?
NSML exhibits a diverse range of symptoms involving different organs and organ systems. Remarkable skin changes are a hallmark feature of Noonan syndrome of multiple lentigines, which become evident and appreciable in the starting phase of teenage. Routinely reported manifestations of NSML to include the following:
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Lentigines: Numerous tiny spots develop all over the body's surface, typically involving the upper trunk (chest), face, and neck area, that are characteristically highly pigmented, exhibited dark brown color. The skin spots start getting evident in the mid-childhood stage and later spread massively over the body during the adolescent period. At the same time, the affected child may exhibit other skin pigmentations like cafe-au-lait-spots as well. These spots are quite lightly pigmented and elicit light brown. Apart from the spots, the skin appears stretchy and loose. Fingers exhibit a webbed appearance restricting individual finger movements.
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Cardiac Abnormalities: NSML is frequently encountered with cardiac defects and abnormalities. Hypertrophic cardiomyopathy is a widely reported cardiac issue, in which there will be an associated stiffening and solidification of the heart muscles. As a result, the blood-pumping process becomes strenuous. It is often accompanied by atypical heart sounds (heart murmur), and the patient may experience chest pain. In addition, NSML also elicits remarkable constriction (narrowing) of the blood vessel, typically involving the pulmonary artery (transporting impure blood to the lungs).
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Facial Deformities: Certain ocular defects like hypertelorism (abnormal spacing between the eyes) and ptosis (drooping eyelids) are frequently seen in association with NSML. These defects significantly influence the facial appearance of the individual. In addition, ears appear wrongly positioned at a lower level, and lips appear bulky and thick.
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Skeletal Defects: NSML completely disrupts the normal chest morphology, and the chest appears either depressed or bulged out. Collapsed chest deformity is known by the name pectus excavatum, while a bulged-out chest is known by the name pectus carinatum.
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Hearing Deficits: Occasionally, certain patients reported deafness in association with NSML.
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Delayed Growth: Affected individuals frequently lag behind in growth and development. The normal expected and intended growth does not occur, which often manifests in the form of short stature despite having normal parameters during birth.
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Intellectual Disability: Significantly compromised mental ability is often elicited in NSML patients.
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Genital Abnormalities: Certain genital abnormalities are frequently encountered in NSML, which generally pose challenges in fertility. Cryptorchidism is occasionally elicited in which the testes fail to come down into the actual position.
How Is Noonan Syndrome With Multiple Lentigines Diagnosed?
Thorough clinical examination and medical history often initiate the diagnosis process. It is not necessary to have all the symptoms in an individual to consider the diagnosis of NSML. Further confirmation of the diagnosis is made with the help of specific diagnostic tests and procedures. Some of the routinely advised tests include the following:
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Electrocardiogram: It is done primarily to detect abnormalities in the heart functioning. In addition, an echocardiogram is also preferred in certain patients to detect defective heart functions.
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Computed Tomography of Brain: It gives a clear picture of the brain and enhances the spotting of defects and irregularities.
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Blood Tests: It is often advised to detect disparity in hormone levels. It not only aids in the diagnosis but also helps in structuring the treatment plans.
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Electroencephalogram: It reveals the electrical process and activities going on in the brain. Thus it aids in the identification of functional irregularities in the brain.
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Biopsy: Specimen collected from the pigmented areas reveals the histopathologic nature of the cells, and thereby helps to rule out other skin conditions.
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Genetic Testing: It facilitates the confirmation of the diagnosis by figuring out the genetic defect that paved the way for NSML.
What Are the Treatment Strategies for Noonan Syndrome With Multiple Lentigines?
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Treatment for Noonan syndrome with multiple lentigines necessitates a multidisciplinary approach as it involves different organ systems.
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The concerned multi-specialty doctors plan the most appropriate treatment strategy.
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Treatment strategies depend largely on the clinical manifestations and extent of organ involvement, and hence, it is individualized.
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Skin spots are often tackled with the help of laser surgery, cryosurgery, excision, and chemical peeling.
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Patients who have hearing deficits are managed with the help of hearing aids. In case of cardiac defects, appropriate treatment should be initiated as per the doctor's advice.
Conclusion:
Noonan syndrome with multiple lentigines is an infrequent condition, that typically exhibits multiorgan involvement. It can have extensive symptoms ranging from skin lesions to skeletal defects. Treatment is often based on the symptoms elicited by an individual, and the treatment strategy is planned accordingly to tackle the manifestations.
