Skip to main content

Table 1 Human patients with RASopathies and their phenotypes

From: The impact of RASopathy-associated mutations on CNS development in mice and humans

DiseaseAssociated genesCNS structural phenotypesOther phenotypes
Neurofibromatosis type 1NF1 (95%) [12]Neurofibromas , abnormal cortical development [13], abnormal glial development [14], macrocephalyBelow-average IQ, ADHD, impaired executive functioning, deficits in visual-spatial skills [15, 16], hyperpigmentation of melanocytes, hamartomas of the iris [17, 18], bone malformation, cardiac defects [19, 20]
Noonan syndrome, Noonan syndrome with multiple lentiginesPTPN11 (>50%) [21], RAF1 (3-17%) [22, 23], SOS1 (9-13%) [24] KRAS (<2%) [25, 26], BRAF (<2%) [22], MEK1/2 (<2%) [27]Cerebellar ectopia [28, 29], temporal lobe anomaly, hydrocephalus, cerebral abscess [30,31,32], epilepsy, cortical dysplasia [33]Neurocognitive delay [33,34,35], typical facial abnormalities, short stature, motor delay, increased risk of cancer, cardiac defects [34,35,36,37,38,39,40]
Cardio-facio-cutaneous syndromeBRAF (43-78%) [41,42,43], MEK1/2 (7-11%) [42, 43], KRAS (5-8%) [25, 43]Ventriculomegaly, hydrocephalus [44,45,46,47,48,49,50], atrophy [44, 46, 51,52,53,54], migration and myelination abnormalities, agenesis of corpus callosum [50, 52, 55,56,57]Neurological abnormalities, seizures, tactile defensiveness, learning disabilities [4, 50, 55], craniofacial defects, cardiac defects [4, 58, 59], motor delay, hypotonia [4, 50, 55]
Costello syndromeHRAS (85-90%) [60,61,62], KRAS (7%) [63], BRAF (4-6%) [27], MEK1/2 (2-3%) [27]Ventricular abnormalities [64,65,66,67], cerebral malformations [64, 65, 67,68,69,70,71], cerebellar abnormalities [66, 69, 71,72,73,74], macrocephaly [59, 60]Mental retardation [59, 60], facial features, loose skin, severe failure to thrive, predisposition to tumors [59, 60]
  1. IQ Intelligence quotient, ADHD Attention deficit hyperactivity disorder;