| Disorder | Genetics | Features of lentigines | Other manifestations |
| Generalized |
| Noonan syndrome with multiple lentigines (LEOPARD syndrome) | - AD
- PTPN11 (nonreceptor protein tyrosine phosphatase) RAF1
| - Onset in infancy/early childhood
- Generalized
- Spare oral mucosa
- Also café-noir and café-au-lait macules
| - Electrocardiogram changes
- Ocular hypertelorism
- Pulmonary stenosis, hypertrophic obstructive cardiomyopathy
- Abnormal genitalia
- Retardation of growth and intellectual disability
- Deafness
- Also triangular facies, skeletal abnormalities
|
| Carney complex (NAME/LAMB syndrome) | - AD
- PRKAR1A (type 1-alpha regulatory subunit of protein kinase A)
| - Onset in early childhood, but the full distribution is not seen until puberty
- Generalized
- May involve eyelids, conjunctiva, vermilion border of lips, genitals
- Usually spare oral mucosa
| - Atrial myxomas
- Mucocutaneous myxomas (often on eyelids, ears, nipples)
- Blue nevi (epithelioid variant)
- Pigmented nodular adrenocortical disease
- Pituitary, thyroid, and testicular (calcifying Sertoli cell) tumors
- Myxoid mammary fibroadenomas
- Psammomatous melanotic schwannomas
|
| Arterial dissection | | - Onset in childhood
- Generalized
| - Dissection of aortic, internal carotid, and vertebral arteries
|
| Localized |
| Peutz-Jeghers syndrome | - AD
- STK11 (serine/threonine protein kinase 11)
| - Onset in infancy/early childhood
- Perioral (may fade), oral mucosa (persist), hands, feet
- Longitudinal melanonychia
| - Multiple hamartomatous gastrointestinal polyps (intussusception may occur)
- Increased incidence of gastrointestinal, ovarian, testicular, cervical (adenoma malignum), pancreatic, and breast cancers
|
| Laugier-Hunziker syndrome | | - As in Peutz-Jeghers
- Also genital melanosis
| - None
- May see similar lesions in patients receiving zidovudine (AZT)
|
| Cowden disease | - AD
- PTEN (phosphatase and tensin homolog)
| - Onset in childhood to young adulthood
- Periorificial and acral lentigines (occasionally seen)
- Café-au-lait macules
| - Facial trichilemmomas
- Oral mucosal cobblestoning
- Acral keratoses
- Lipomas, sclerotic fibromas
- Macrocephaly, adenoid facies, mental retardation
- Thyroid adenomas/carcinoma
- Breast fibroadenomas/carcinoma
- Gastrointestinal hamartomas/carcinoma
- Uterine fibroids/carcinoma
|
| Bannayan-Riley-Ruvalcaba syndrome | - AD
- PTEN (phosphatase and tensin homolog)
| - Genital melanosis
- Café-au-lait macules
| - Capillary and/or venous malformations
- Lipomas
- Facial trichilemmomas
- Acanthosis nigricans
- Macrocephaly, mental retardation
- Gastrointestinal hamartomas
- Thyroid tumors
|
| Centrofacial lentiginosis | | - Onset in infancy; increase in number in childhood
- Butterfly distribution on nose and cheeks > forehead, eyelids, upper lip
| - Neuropsychiatric disorders
- Osseous anomalies
|
| Inherited patterned lentiginosis | - AD
- Black individuals with light brown skin
| - Central face, lips > buttocks, elbows, hands, feet
- Usually spare oral mucosa
| |
| Partial unilateral lentiginosis | | - Onset in childhood, with wavefront extension over time
- Segmental distribution (no background hyperpigmentation)
- Often have café-au-lait macules in same area
- Can have ocular lesions
| - May be associated with segmental neurofibromatosis
- A few reports of associated mental retardation and seizures
|
| Xeroderma pigmentosum | - AR
- XP-A through G and variant (abnormal nucleotide excision repair)
| - Favor (but not limited to) sun-exposed sites (represent solar lentigines)
| - Photosensitivity
- Markedly increased incidence of basal and squamous cell carcinomas and melanoma
- Also increased incidence of internal malignancies
- CNS degeneration in a subset of patients
|
| Neurofibromatosis type 1 | | - "Freckling" (actually represents lentigines) favors flexural sites (neck, axillae, groin), but may be generalized
- ≥6 café-au-lait macules (in 80 to 90% of patients)
| - Cutaneous neurofibromas
- Lisch nodules (iris hamartomas)
- Optic glioma
- Distinct bone lesions (eg, sphenoid dysplasia)
- Macrocephaly
- Learning disabilities
|
| Legius (neurofibromatosis type 1-like) syndrome | - AD
- SPRED1 (Sprouty-related EVH1 domain containing protein 1)
| - Intertriginous "freckling" (actually lentigines) in approximately half of patients
- ≥6 café-au-lait macules in >80% of patients
| - Lacks neurofibromas, Lisch nodules, optic gliomas, and typical osseous lesions of neurofibromatosis type 1
- Macrocephaly and learning disabilities are common
- Occasionally lipomas, hypopigmented macules, and vascular anomalies
|
