From: Mutation in NRAS in familial Noonan syndrome – case report and review of the literature
# | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 9 M | 10 | 11 | 12 | 12 F |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Patient | De Filippi et al. [20] | Runtuwene et al. [21] | Denayer et al. [22] | Denayer et al. [22] | Denayer et al. [22] | Cirstea et al. [14] | Cirstea et al. [14] | Cirstea et al. [14] | Cirstea et al. [14] | Cirstea et al. [14] | Kraoua et al. [23] | Kraoua et al. [23] | Present study | Present study |
NRAS mutation | p.G13D | p.I24N | p.I24N | p.P24L | p.T50I | p.T50I | p.T50I | p.G60E | p.G60E | p.G60E | p.G60E | p.G60E | p.G60E | p.G60E |
Origin of mutation | de novo | de novo | de novo | Inherited | ND | de novo | de novo | de novo | Inherited | ND | ND (probably inherited) | de novo | Inherited | ND (probably inherited) |
Paternal age at conception | ND | 26 years | ND | ND | ND | 50 years | 34 years | 31 years | 47 years | 44 years | 45 years | 47 years | 34 years | ND |
Age at last examination | 3 years | 30 years | 13 years | 19 years | 2.5 years | 14 years | 7 years | 3.3 years | 20 years | 50 years | 24 years | 3 months | 28 years | 62 years |
Gender | Male | Male | Male | Male | Male | Male | Male | Female | Male | Female | Male | Female | Female | Male |
Prenatal findings | ND | Polyhydramnios | ND | ND | ND | Nuchal edema, Polyhydramnios | Polyhydramnios | Single umbilical artery | - | - | Polyhydramnios | Pyelectasis | - | - |
Congenital heart defect | - | - | - | ND | Coarctation aortae, Patent foramen ovale | HCM | PS | Mild HCM, Mitral valve dysplasia, PS | - | - | - | PS | ASD, HCM | Cardiac murmur |
Rythm disturbance | ND | - | ND | ND | - | SVES | - | - | - | - | - | - | - | - |
Typical facial features | + | + | + | + | + | + | + | + | + | + | + | + | + | + |
Stature | 5–10th centile | Mild short | <3rd centile | 10th–25th centile | 10th–25th centile | 10th centilea | <3rd centile | <3rd centile | >10th centile | 10th centile | 3rd centile | 3rd–10th centile | 50th centilea | 50th centile |
Macrocephaly | Relative | >90th centile | >97th centile | ND | 25th–50th centile | + | Relative | - | + | + | Relative | Relative | + | Relative |
Pterygium colli/Webbed neck | - | + | ND | ND | + | + | - | + | + | + | + | + | + | + |
Thorax deformity | - | Pectus excavatum | Pectus excavatum | ND | Pectus excavatum | + | - | Pectus excavatum | + | + | Mildly depressed thorax | Pectus excavatum | - | - |
Easy bruising | - | - | ND | + | ND | - | - | - | - | - | + | ND | + | - |
Cryptorchidism | - | + | + | ND | + | + | + | NA | + | NA | - | NA | NA | - |
Ophthalmological problems | ND | - | Strabismus, Bilateral keratoconus of the cornea | ND | ND | Myopia | - | - | - | Myopia | - | - | Astigmatis, Myopia, Strabismus | - |
Motor delay/Muscular hypotonia | - | Motor delay | Mild | ND | ND | Mild | + | + | + | + | Mild | + | - | - |
Mental development | Normal | Mild learning difficulties | Normal | Learning difficulties | Normal | Normal | Borderline | Speech delay | Normal-borderline | Normal | Speech delay, dyscalculy | NA | ADHD, normal IQ | Normal |
Keratosis pilaris/Hyperkeratosis | ND | - | ND | ND | ND | Severe | - | + | + | + | ND | - | - | - |
Hair abnormalities | - | - | ND | ND | ND | Curly hair | Curly hair | Sparse thin hair | Curly hair | - | - | Curly hair | - | Curly hair |
Lentigines/Café-au-lait spots | + | Some lentigines | - | - | - | - | - | - | - | - | + | + | + | + |
Leukemia/Cancer | JMML | - | - | - | - | - | - | - | - | - | - | - | - | - |
Other | - | Oligospermia | - | Inadequate visio-spatial orientation skills, Inguinal hernia, Delayed pubertal development | - | Pes equinovarus | - | Palpebral ptosis | Ichtyosiform eczema, Acanthosis nigricans, Scoliosis | Mother of patient 9 | Palpebral ptosis, Inguinal hernia, Scoliosis | Palpebral ptosis, Unilateral pyelectasis | - | Sensory-neural hearing deficit, Father of patient 12 |