MedGen

Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck, and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth restriction resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th centile for age. Sensorineural hearing deficits, present in approximately 20% of affected individuals, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML. [from GeneReviews]

Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck, and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth restriction resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th centile for age. Sensorineural hearing deficits, present in approximately 20% of affected individuals, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML. [from GeneReviews]

Carney complex (CNC) is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of CNC and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and can manifest as intracardiac obstruction of blood flow, embolic phenomenon, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease (PPNAD), which causes Cushing syndrome, is the most frequently observed endocrine tumor in CNC, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one third of affected males within the first decade and in most adult males. Up to 75% of individuals with CNC have multiple thyroid nodules, most of which are nonfunctioning thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. The median age of diagnosis is 20 years. [from GeneReviews]

Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck, and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth restriction resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th centile for age. Sensorineural hearing deficits, present in approximately 20% of affected individuals, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML. [from GeneReviews]

Noonan syndrome with multiple lentigines (NSML) is a condition in which the cardinal features consist of lentigines, hypertrophic cardiomyopathy, short stature, pectus deformity, and dysmorphic facial features including widely spaced eyes and ptosis. Multiple lentigines present as dispersed flat, black-brown macules, mostly on the face, neck, and upper part of the trunk with sparing of the mucosa. In general, lentigines do not appear until age four to five years but then increase to the thousands by puberty. Some individuals with NSML do not exhibit lentigines. Approximately 85% of affected individuals have heart defects, including hypertrophic cardiomyopathy (typically appearing during infancy and sometimes progressive) and pulmonary valve stenosis. Postnatal growth restriction resulting in short stature occurs in fewer than 50% of affected persons, although most affected individuals have a height that is less than the 25th centile for age. Sensorineural hearing deficits, present in approximately 20% of affected individuals, are poorly characterized. Intellectual disability, typically mild, is observed in approximately 30% of persons with NSML. [from GeneReviews]

Congenital melanocytic nevus syndrome is characterized by pigmentary skin defects apparent at birth. Most individuals have 1 or more large or giant lesions greater than 20 cm and up to over 60 cm in diameter, which may cover up to 80% of total body area. These lesions may or may not be hairy. Smaller 'satellite' pigmented lesions numbering in the hundreds may also be present all over the body. Congenital melanocytic nevi (CMN) can be associated with malignant melanoma (see CMM1, 155600), but the risk appears to be low, ranging from 1 to 2% for all individuals, but rising to 10 to 15% in those with very large nevi (greater than 40 cm). A small subset of patients with CMNS have abnormalities of the central nervous system, known as 'neurocutaneous melanosis' or 'neuromelanosis' (249400), which may be symptomatic. Patients with CMNS also tend to have a characteristic facial appearance, including wide or prominent forehead, periorbital fullness, small short nose with narrow nasal bridge, round face, full cheeks, prominent premaxilla, and everted lower lip (summary by Kinsler et al., 2008; Kinsler et al., 2012). Spitz nevi are benign melanocytic melanomas composed of epithelioid or spindle cell melanocytes. They usually present as solitary skin tumors but can occur in multiple patterns, having agminated, dermatomal, and disseminated forms (summary by Sarin et al., 2013). Nevus spilus, also known as speckled lentiginous nevus, is a congenital hyperpigmented patch that progressively evolves, with affected individuals developing dark macules and papules during childhood and adolescence. Over time, nevus spilus may give rise to common lentigines, melanocytic nevi, Spitz nevi, and melanomas (summary by Sarin et al., 2014). [from OMIM]

A group of genetic disorders associated with mutation(s) in genes that are constituents of the RAS signaling pathway. These disorders are characterized by distinct facial features, developmental delays, cardiac defects, growth delays, and feeding problems. Representative examples include: neurofibromatosis type 1, capillary malformation-arteriovenous malformation syndrome, cardiofaciocutaneous syndrome, Costello syndrome, multiple lentigines syndrome, and Noonan syndrome. [from NCI]

Carney complex (CNC) is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of CNC and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and can manifest as intracardiac obstruction of blood flow, embolic phenomenon, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease (PPNAD), which causes Cushing syndrome, is the most frequently observed endocrine tumor in CNC, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one third of affected males within the first decade and in most adult males. Up to 75% of individuals with CNC have multiple thyroid nodules, most of which are nonfunctioning thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. The median age of diagnosis is 20 years. [from GeneReviews]

Presence of an unusually high number of lentigines (singular [from HPO]

Dyschromatosis universalis hereditaria (DUH) is a rare autosomal dominant genodermatosis characterized by irregularly shaped, asymptomatic hyper- and hypopigmented macules that appear in infancy or early childhood and occur in a generalized distribution over the trunk, limbs, and sometimes the face. Involvement of the palms or soles is unusual. Abnormalities of hair and nails have been reported, and DUH may be associated with abnormalities of dermal connective tissue, nerve tissue, or other systemic complications (summary by Zhang et al., 2013). The autosomal dominant SASH1-associated DUH1 phenotype is characterized by generalized lentigines accompanied by mottled hyper- and hypopigmentation (Zhang et al., 2017). DUH is distinct from dyschromatosis symmetrica hereditaria (DSH; 127400), which also occurs particularly in Japanese and Korean individuals, but shows a characteristic mixture of hyper- and hypopigmented macules limited largely to the dorsal aspects of the hands and feet (Suenaga, 1952). Gao et al. (2005) noted that lesions associated with DUH appear within the first year of life predominantly on the trunk, whereas the age of onset of DSH is approximately 6 years and lesions appear predominantly on the extremities. Genetic Heterogeneity of Dyschromatosis Universalis Hereditaria Dyschromatosis universalis hereditaria-2 (DUH2; 612715) maps to chromosome 12q21-q23. DUH3 (615402) is caused by mutation in the ABCB6 gene (605452) on chromosome 2q35. [from OMIM]

Carney complex (CNC) is characterized by skin pigmentary abnormalities, myxomas, endocrine tumors or overactivity, and schwannomas. Pale brown to black lentigines are the most common presenting feature of CNC and typically increase in number at puberty. Cardiac myxomas occur at a young age, may occur in any or all cardiac chambers, and can manifest as intracardiac obstruction of blood flow, embolic phenomenon, and/or heart failure. Other sites for myxomas include the skin, breast, oropharynx, and female genital tract. Primary pigmented nodular adrenocortical disease (PPNAD), which causes Cushing syndrome, is the most frequently observed endocrine tumor in CNC, occurring in approximately 25% of affected individuals. Large-cell calcifying Sertoli cell tumors (LCCSCTs) are observed in one third of affected males within the first decade and in most adult males. Up to 75% of individuals with CNC have multiple thyroid nodules, most of which are nonfunctioning thyroid follicular adenomas. Clinically evident acromegaly from a growth hormone (GH)-producing adenoma is evident in approximately 10% of adults. Psammomatous melanotic schwannoma (PMS), a rare tumor of the nerve sheath, occurs in an estimated 10% of affected individuals. The median age of diagnosis is 20 years. [from GeneReviews]

A flat, benign, pigmented spot on the skin caused by excessive deposition of melanin from an increased number of melanocytes in the cell layer directly above the basement membrane of the epidermis. Formation is usually related to sun exposure during youth, and the lesions do not typically progress to malignancy. [from NCI]

A rare association syndrome, reported in several members of two families to date, characterized by arterial dissection, occurring at an early age and presenting with a range of manifestations depending on the vascular territory involved (ex. headache, dysphasia, hemiparesis), in association with cystic medial necrosis and multiple lentigines (brown and black in color and mainly affecting the skin of the trunk and extremities). [from ORDO]

Familial generalized lentiginosis is a rare, inherited, skin hyperpigmentation disorder characterized by widespread lentigines without associated noncutaneous abnormalities. Patients present multiple brown to dark brown, non-elevated macula of 0.2 to 1 cm in diameter, spread over the entire body, sometimes including palms or soles, but never oral mucosa. [from ORDO]

A rare syndromic hyperpigmentation of the skin with characteristics of multiple lentigines and cafe-au-lait spots associated with hiatal hernia and peptic ulcer, hypertelorism and myopia. There have been no further descriptions in the literature since 1982. [from SNOMEDCT_US]

A rare genetic skin pigmentation anomaly disorder with characteristics of progressive, diffuse, partly blotchy, hyperpigmented lesions that are intermixed with multiple cafe au lait spots, hypopigmented maculae and lentigines and are located on the face, neck, trunk and limbs, as well as, frequently, the palms, soles and oral mucosa. Dyspigmentation pattern can range from well isolated cafe au lait/hypopigmented patches on a background of normal-appearing skin to confetti-like or mottled appearance. There is evidence this disease is caused by heterozygous mutation in the KIT ligand gene (KITLG) on chromosome 12q22. [from SNOMEDCT_US]

A rare genetic multiple congenital anomalies/dysmorphic syndrome with characteristics of facial dysmorphism (mild eyelid ptosis, xanthelasma, anteverted nostrils, bifid nasal tip, short palate), severe muscle wasting and cachexia, retinitis pigmentosa, numerous lentigines and cafe-au-lait spots, as well as mild soft tissue syndactyly. Additional features include nasal speech, chest asymmetry, pectus excavatum, genu varum, pes planus, and thyroid papillary carcinoma and diffuse enlargement. There has been no further description in the literature since 1984. [from SNOMEDCT_US]