Table 1.
Demographic and Clinical Characterization of Individuals with a Missense Mutation Affecting Codons 844–848
| Mutation [Proband:Relative] |
Codon 844 |
Codon 845 |
Codon 846 |
Codon 847 |
Codon 848 |
All Codons 844–848 | Total | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| c.2530C>T (p.Leu844Phe) [10:1]; c.2531T>A (p.Leu844His) [2:0]; c.2531T>C (p.Leu844Pro) [7:0]; c.2531T>G (p.Leu844Arg) [6:0] | c.2533T>C (p.Cys845Arg) [3:1]; c.2534G>A (p.Cys845Tyr) [8:0] | c.2536G>C (p.Ala846Pro) [1:2]; c.2537C>A (p.Ala846Asp) [5:2] | c.2540T>C (p.Leu847Pro) [58:12]; c.2540T>G (p.Leu847Arg) [8:0] | c.2542G>A (p.Gly848Arg) [6:0]; c.2542G>C (p.Gly848Arg) [8:11]; c.2543G>A (p.Gly848Glu) [7:4] | |||||||||||||||
| Mutation-positive individuals [Proband:Relative] | 26 [25:1] | 12 [11:1] | 10 [6:4] | 78 [66:12] | 36 [21:15] | 162 [129:33] | |||||||||||||
| Age group, years | ≤8 | 9–18 | ≥19 | ≤8 | 9–18 | ≥19 | ≤8 | 9–18 | ≥19 | ≤8 | 9–18 | ≥19 | ≤8 | 9–18 | ≥19 | ≤8 | 9–18 | ≥19 | all ages |
| Total | 12 | 5 | 9 | 4 | 2 | 6 | 3 | 1 | 6 | 28 | 14 | 36 | 13 | 5 | 18 | 60 | 27 | 75 | 162 |
| Proband:Relative | 12:0 | 5:0 | 8:1 | 4:0 | 2:0 | 5:1 | 2:1 | 1:0 | 3:3 | 27:1 | 12:2 | 27:9 | 6:7 | 4:1 | 11:7 | 51:9 | 24:3 | 54:21 | 129:33 |
| Age range, years | 1–8 | 9–16 | 24–55 | 1–2 | 15–16 | 19–48 | 4–5 | 18 | 33–69 | 1–8 | 9–18 | 19–72 | 1–7 | 10–17 | 19–74 | 1–8 | 9–18 | 19–74 | 1–74 |
| Male: Female | 6:6 | 4:1 | 1:8 | 1:3 | 1:1 | 1:5 | 2:1 | 0:1 | 1:5 | 10:18 | 5:9 | 19:17 | 9:4 | 2:3 | 5:13 | 28:32 | 12:15 | 27:48 | 67:95 |
| Fulfilling the NIH criteria if the family history is taken into account | 10/11 | 4/5 | 9/9 | 2/4 | 1/2 | 4/5 | 3/3 | 1/1 | 6/6 | 17/28 | 14/14 | 35/36 | 4/11 | 4/5 | 17/18 | 36/57 | 24/27 | 71/74 | 131/158 |
| Fulfilling the NIH criteria if solely taking the physical signs into account | 10/11 | 4/5 | 9/9 | 2/4 | 1/2 | 4/5 | 2/3 | 1/1 | 6/6 | 17/28 | 14/14 | 33/36 | 4/11 | 4/5 | 13/18 | 35/57 | 24/27 | 65/74 | 124/158 |
| >5 CALMs | 12/12 | 5/5 | 8/8 | 4/4 | 1/2 | 4/5 | 3/3 | 1/1 | 4/6 | 27/28 | 14/14 | 32/35 | 5/11 | 3/5 | 7/18 | 51/58 | 24/27 | 55/72 | 130/157 |
| Freckling | 10/10 | 4/5 | 6/7 | 0/4 | 1/2 | 4/5 | 2/2 | 1/1 | 5/5 | 12/23 | 13/13 | 31/34 | 4/10 | 3/5 | 8/18 | 28/49 | 22/26 | 54/69 | 104/144 |
| Lisch nodules | 2/9 | 1/4 | 4/4 | 0/1 | 0/0 | 1/2 | 0/1 | 0/1 | 2/2 | 4/19 | 3/9 | 17/19 | 2/8 | 0/5 | 6/14 | 8/38 | 4/19 | 30/41 | 42/98 |
| Skeletal abnormalitiesa | 2/11 | 2/5 | 5/9 | 2/4 | 1/2 | 2/4 | 0/2 | 0/1 | 0/5 | 3/25 | 3/14 | 17/28 | 3/11 | 3/5 | 5/18 | 10/53 | 9/27 | 29/64 | 48/144 |
| Plexiform neurofibromas | 0/11 | 2/5 | 3/9 | 0/3 | 2/2 | 2/5 | 0/2 | 1/1 | 1/2 | 6/24 | 3/13 | 19/33 | 0/11 | 1/5 | 7/17 | 6/51 | 9/26 | 32/66 | 47/143 |
| Cutaneous neurofibromasb | 1/11 | 1/5 | 7/9 | 0/4 | 0/2 | 3/4 | 0/2 | 1/1 | 4/5 | 1/26 | 4/14 | 28/33 | 1/11 | 1/5 | 5/18 | 3/54 | 7/27 | 47/69 | 57/150 |
| Subcutaneous neurofibromasb | 1/9 | 0/5 | 6/8 | 1/4 | 0/2 | 1/4 | 0/2 | 0/0 | 3/5 | 1/26 | 4/13 | 17/30 | 1/11 | 0/5 | 6/18 | 4/52 | 4/25 | 33/65 | 41/142 |
| Cutaneous and subcutaneousb | 0/9 | 0/5 | 5/8 | 0/4 | 0/2 | 1/3 | 0/2 | 0/0 | 3/5 | 0/25 | 1/13 | 17/30 | 0/11 | 0/5 | 4/18 | 0/51 | 1/25 | 30/64 | 31/140 |
| Symptomatic spinal neurofibromas | 0/10 | 0/3 | 0/8 | 0/2 | 1/2 | 0/4 | 0/2 | 0/0 | 0/2 | 1/23 | 1/13 | 2/27 | 0/11 | 1/4 | 7/16 | 1/48 | 3/22 | 9/57 | 13/127 |
| Spinal neurofibromas by MRIc | 0/1 | 0/0 | 0/5 | 0/0 | 1/2 | 1/1 | 0/1 | 0/0 | 0/1 | 1/5 | 2/6 | 3/16 | 0/1 | 2/3 | 10/11 | 1/8 | 5/11 | 14/34 | 20/53 |
| Symptomatic OPGsd | 1/11 | 1/5 | 0/9 | 0/3 | 0/2 | 0/5 | 1/3 | 1/1 | 0/3 | 2/25 | 1/13 | 2/27 | 1/11 | 1/5 | 1/13 | 5/53 | 4/26 | 3/57 | 12/136 |
| Asymptomatic OPGse | 2/6 | 1/2 | 2/4 | 0/1 | 0/2 | 0/2 | 0/1 | 0/0 | 0/3 | 1/8 | 6/9 | 4/13 | 1/4 | 0/2 | 1/6 | 4/20 | 7/15 | 7/28 | 18/63 |
| Other neoplasmsf | 1/11 | 0/4 | 1/8 | 0/2 | 0/1 | 0/4 | 0/2 | 0/1 | 0/3 | 1/24 | 3/14 | 11/34 | 2/11 | 1/5 | 1/15 | 4/50 | 4/25 | 13/64 | 21/139 |
| Cognitive impairment and/or learning disabilities | 3/11 | 3/4 | 0/6 | 1/4 | 0/2 | 3/4 | 3/3 | 0/1 | 1/5 | 10/26 | 7/13 | 12/26 | 5/11 | 5/5 | 3/17 | 22/55 | 15/25 | 19/58 | 56/138 |
| Noonan syndrome features | 0/9 | 1/5 | 1/8 | 0/2 | 1/1 | 0/4 | 0/2 | 0/1 | 0/4 | 3/27 | 0/13 | 3/26 | 1/10 | 0/5 | 0/17 | 4/50 | 2/25 | 4/59 | 10/134 |
| Short statureg | 1/7 | 0/2 | 0/4 | 0/3 | 1/1 | 0/1 | 0/2 | 0/0 | 1/2 | 0/11 | 3/10 | 4/21 | 3/10 | 0/3 | 2/14 | 4/33 | 4/16 | 7/42 | 15/91 |
| Macrocephaly | 2/11 | 1/4 | 1/2 | 1/3 | 0/1 | 0/0 | 2/2 | 0/0 | 0/2 | 8/21 | 2/11 | 10/17 | 3/11 | 1/4 | 5/9 | 16/48 | 4/20 | 16/30 | 36/98 |
| Pulmonic stenosis | 0/8 | 1/5 | 0/6 | 0/2 | 0/2 | 1/1 | 0/3 | 0/0 | 0/5 | 0/23 | 0/13 | 0/20 | 0/8 | 0/3 | 0/14 | 0/44 | 1/23 | 1/46 | 2/113 |
All bone abnormalities included, i.e., scoliosis (n = 27), pectus excavatum (n = 4), pectus carinatum (n = 6), long bone dysplasia (n = 4), pseudarthrosis (n = 2), bone cysts (n = 2), sphenoid wing dysplasia (n = 2), ulnar aplasia, dural ectasia, 4th lumbar vertebrae fragmentation, bowed long bones, tibial dysplasia, clinodactyly, postaxial polydactyly, and cherubism.
At least two cutaneous/subcutaneous neurofibromas were required to be considered as “positive for the criterion of neurofibromas.”
The frequency of both symptomatic and asymptomatic spinal neurofibromas in individuals who had done MRI examination.
The presence or absence of symptomatic OPGs was determined by ophthalmological examination and confirmed by MRI.
Including only individuals without signs of symptomatic OPGs who underwent MRI examination.
Including benign and malignant neoplasms, except for OPGs and neurofibromas.
As no specific growth curves are available for the Hispanic and Asian populations, Hispanic and Asian individuals were excluded as having short or normal stature.