Differential Diagnosis of Patients With CALMs

DiagnosisClinical Features
Legius syndrome• Typical NF1-like CALMs; mild freckling
• No neurofibromas or OPGs
• Similar cognitive impairment
McCune-Albright syndrome• Jagged (coast of Maine) CALMs
• Polyostotic fibrous dysplasia with fracture
• Precocious puberty or other tumors
• No neurofibromas
Noonan syndrome• Typical CALMs but fewer
• Lentigines rather than Crowe sign freckling
• Pulmonic valve stenosis with neck webbing
• Short stature, cryptorchidism, pectus excavatum, curly hair, distinctive facial gestalt
Silver-Russell syndrome• Typical CALMs but fewer; no freckling
• Intrauterine growth retardation with postnatal growth retardation, normocephaly
• Fifth digit clinodactyly, hypospadias, body asymmetry
Chromosomal or DNA instability syndromes: FS, BS, MMRCS• Atypical CALMs; no freckles
• Postnatal growth retardation with microcephaly
• UV sensitivity (BS), brain and blood cancers (MMRCS), congenital malformations (FS)
PTEN hamartoma tumor syndrome• Typical CALMs but fewer; no freckles
• CALMs of the glans and/or penile shaft in males
• Macrocephaly (≥3 SD from mean)
• Hypotonia, family history of thyroid and breast cancer
Chromosomal mosaicism and ring chromosomes• Atypical CALMs; pigmentary dysplasia
• Intellectual disability
• Growth retardation with microcephaly
• Body asymmetry
Sotos syndrome, Nevoid basal cell carcinoma syndrome, neurofibromatosis type 2, epidermal nevus syndrome, Carney syndrome• Atypical CALMs; no freckling
• Physical manifestations distinct from NF1
  • BS, Bloom syndrome; FS, Fanconi syndrome; MMRCS, mismatch repair cancer syndrome; PTEN, Phosphatase and tensin homolog.