Table 1 Syndromes associated with café-au-lait macules
From: Diagnostic and pathogenetic role of café-au-lait macules in nevoid basal cell carcinoma syndrome
Syndrome | Gene or Locus | Cutaneous Clinical Features | Systemic Clinical Features |
|---|---|---|---|
NF1 | NF1 | Multiple café-au-lait (>6), skin-fold freckling, cutaneous and plexiform neurofbromas | Macrocephaly, optic pathway glioma, skeletal dysplasia |
NF2 | NF2 | Café-au-lait macules seen but not a criterion for diagnosis, neurofibromas | Acoustic neuromas, schwannomas, meningiomas, juvenile posterior subcapsular lenticular opacity |
Multiple familial Café-au-lait | Unknown | Multiple café-au-lait | Without other stigmata of NF1 |
Legius (NF-1 like) syndrome | SPREAD1 | Multiple café-au-lait, skin-fold freckling | Without other stigmata of NF1 |
McCune Albright syndrome | GNAS1 | Segmental café-au-lait | Precocious puberty, other endocrinopathies, polyostotic fibrous dysplasia |
Constitutional MMR deficiency syndrome | MLH1, MSH2, MSH6, PMS2 | Multiple café-au-lait | Adenomatous colonic polyps, multiple malignancies (medulloblastoma, lymphoma, glioblastoma) |
Ring chromosome syndrome | Choromosomes 7,11,12,15,17 | Multiple café-au-lait | Microcephaly, mental retardation, short stature |
Leopard/multiple lentigenes syndrome | PTPN11 | Café-au-lait, café-noir, lentigines | Cardiac conduction defects, ocular hypertelorism, pulmonary stenosis, growth retardation, hearing loss |
Cowden syndrome | PTEN | Café-au-lait spots, Facial trichilemmomas, soft tissue tumors (lipomas, neuromas) | Cobblestoning of the oral mucosa, gastrointestinal polyps, breast carcinoma, thyroid adenoma and cancer |
Banayan-Riley- Ruvalcaba syndrome | PTEN | Pigmented genital macules, Facial trichilemmomas | Oral papillomas, gastrointestinal polyps, Macrocephaly, vascular anomalies |
WEAK ASSOCIATION | |||
NAME (naevi, atrial mixoma, ephelides) syndrome | Unknown | Naevi, ephelides | Atrial mixoma |
Ataxia teleangectasia | ATM | Cutaneous and ocular teleangectasias | Cerebellar ataxia, immunodeficiency, hypogonadism, lymphoreticular malignancy |
Epidermal Nevus syndrome | Unknown | Linear epidermal nevus | Mental retardation, seizures, movement disorders |
Turner Syndrome | X-chromosomal anomalies (XO karyotupe or Xp deletion) | Cutaneous lymphatic malformations | Short stature, broad chest, low hairline, low-set ears and webbed necks, swelling, gonadal dysfunction, congenital heart disease, hypothyroidism. |
Silver-Russel Syndrome | Unknown | Multiple café au lait macules | Short stature, craniofacial and body asymmetry, microcephaly, congenital cardiac defects |
Fanconi Anemia | FANCA, FANCB/C/D locus on chromosome 3, FANCE/F/G/H | Hyper- and hypopigmentation of the skin, mucocutaneous squamous cell carcinomas | Bone marrow failure, multiple congenital anomalies, mental retatrdation, microcephaly |
Westerhof Syndrome | unknown | Hypopigmented and hyperpigmented macules | Retarded growth and mental deficiency |
MEN1/Men2B | RET | Multiple malignancies | |
Bloom syndrome | RECQL3 | Hypo- and hyper-pigmented spots; telangiectasias | Mental retardation, short stature |
Gaucher Disease | Chromosome 1 | Yellowish-brown skin pigmentation | Astenia, diarrhoea, ataxia, splenomegalia, hemorrhagies, muscolar atrophia, |
Hunter Disease | X-linked | Skin eruptions | Macrocephaly, mental retardation, valvular dysfunction |
Watson Syndrome | NF1 | Axillary/inguinal freckling | Mental retardation, short stature, pulmonary valvular stenosis, Lisch nodules |