Table 2 Significant associations between variants in domains and clinical features (p-value < 0.001).
From: Protein domain-specific genotype–phenotype correlation study of neurofibromatosis type 1
Age | Clinical features | Group | Variants in the category n/N (%) | Variants outside the category n/N (%) | OR [95% C.I.] | P-value* |
|---|---|---|---|---|---|---|
Domain: CSRD | ||||||
≥ 8 yr# | CALMs | NIH criteria | 179/201 (89.05%) | 950/993 (95.67%) | 0.37 [0.21–0.66] | < 0.001 (Other) |
≥ 8 yr | Lisch nodules | NIH criteria | 76/160 (47.50%) | 247/810 (30.49%) | 2.06 [1.44–2.95] | < 0.001 (Domain) |
≥ 8 yr | Plexiform neurofibroma | NIH criteria | 65/183 (35.52%) | 151/908 (16.63%) | 2.76 [1.91–3.97] | < 0.001 (Domain) |
≥ 8 yr | Cutaneous neurofibroma | NIH criteria | 137/194 (70.62%) | 416/852 (48.83%) | 2.52 [1.78–3.59] | < 0.001 (Domain) |
All | MRI brain abnormalities | Others | 67/135 (49.63%) | 181/639 (28.33%) | 2.49 [1.67–3.70] | < 0.001 (Domain) |
Domain: TBD | ||||||
≥ 8 yr | Cutaneous neurofibroma | NIH criteria | 19/69 (27.54%) | 534/977 (54.66%) | 0.32 [0.17–0.55] | < 0.001 (Other) |
All | Hypertelorism | Noonan-syndrome facial features | 22/48 (45.83%) | 153/778 (19.67%) | 3.45 [1.81–6.52] | < 0.001 (Domain) |
All | Speech delay | Neurological and behavioural features | 14/43 (32.56%) | 95/759 (12.52%) | 3.37 [1.58–6.86] | < 0.001 (Domain) |
Domain: GRD | ||||||
All | Hypertelorism | Noonan-syndrome facial features | 52/160 (32.50%) | 123/666 (18.47%) | 2.12 [1.41–3.17] | < 0.001 (Domain) |
All | Ptosis | Noonan-syndrome facial features | 65/178 (36.52%) | 106/696 (15.23%) | 3.20 [2.17–4.70] | < 0.001 (Domain) |
≥ 8 yr | Short Stature | Growth and musculoskeletal features | 34/116 (29.31%) | 61/501 (12.18%) | 2.98 [1.78–4.95] | < 0.001 (Domain) |
All | Speech delay | Neurological and behavioural features | 35/144 (24.31%) | 74/658 (11.25%) | 2.53 [1.56–4.05] | < 0.001 (Domain) |
All | Congenital heart disease | Cardiovascular abnormalities | 56/308 (18.18%) | 70/1018 (6.88%) | 3.01 [2.02–4.46] | < 0.001 (Domain) |
Domain: PH | ||||||
≥ 8 yr | Lisch nodules | NIH criteria | 10/91 (10.99%) | 313/879 (35.61%) | 0.22 [0.10–0.44] | < 0.001 (Other) |
≥ 8 yr | Plexiform neurofibroma | NIH criteria | 3/123 (2.44%) | 213/968 (22.00%) | 0.09 [0.02–0.27] | < 0.001 (Other) |
All | Ptosis | Noonan-syndrome facial features | 42/66 (63.64%) | 129/808 (15.97%) | 9.18 [5.23–16.44] | < 0.001 (Domain) |
≥ 8 yr | Short Stature | Growth and musculoskeletal features | 18/54 (33.33%) | 77/563 (13.68%) | 3.15 [1.60–6.03] | < 0.001 (Domain) |
≥ 8 yr | Pectus deformity | Growth and musculoskeletal features | 16/46 (34.78%) | 37/607 (6.10%) | 8.16 [3.80–17.14] | < 0.001 (Domain) |
All | Delayed cognitive development | Neurological and behavioural features | 86/165 (52.12%) | 348/1254 (27.75%) | 2.83 [2.01–3.99] | < 0.001 (Domain) |
All | Speech delay | Neurological and behavioural features | 17/38 (44.74%) | 92/764 (12.04%) | 5.89 [2.81–12.22] | < 0.001 (Domain) |
All | ADHD | Neurological and behavioural features | 14/37 (37.84%) | 110/767 (14.34%) | 3.63 [1.67–7.62] | < 0.001 (Domain) |
Domain: HLR | ||||||
All | Hypertelorism | Noonan-syndrome facial features | 13/150 (8.67%) | 162/676 (23.96%) | 0.30 [0.15–0.55] | < 0.001 (Other) |
All | Ptosis | Noonan-syndrome facial features | 8/149 (5.37%) | 163/725 (22.48%) | 0.20 [0.08–0.41] | < 0.001 (Other) |
All | Delayed cognitive development | Neurological and behavioural features | 14/147 (9.52%) | 420/1272 (33.02%) | 0.21 [0.11–0.38] | < 0.001 (Other) |
All | Speech delay | Neurological and behavioural features | 1/147 (0.68%) | 108/655 (16.49%) | 0.03 [0.00–0.20] | < 0.001 (Other) |
All | ADHD | Neurological and behavioural features | 10/147 (6.80%) | 114/657 (17.35%) | 0.35 [0.16–0.69] | < 0.001 (Other) |
All | Congenital heart disease | Cardiovascular abnormalities | 3/149 (2.01%) | 123/1177 (10.45%) | 0.18 [0.04–0.54] | < 0.001 (Other) |
Domain: CTD | ||||||
All | Ptosis | Noonan-syndrome facial features | 1/91 (1.10%) | 170/783 (21.71%) | 0.04 [0.00–0.23] | < 0.001 (Other) |
All | Delayed cognitive development | Neurological and behavioural features | 11/90 (12.22%) | 423/1329 (31.83%) | 0.30 [0.14–0.57] | < 0.001 (Other) |
Not in domains | ||||||
≥ 8 yr | Cutaneous neurofibroma | NIH criteria | 144/320 (45.00%) | 409/727 (56.26%) | 0.64 [0.48–0.84] | < 0.001 (Other) |
All | Ptosis | Noonan-syndrome facial features | 27/261 (10.34%) | 144/614 (23.45%) | 0.38 [0.23–0.59] | < 0.001 (Other) |
≥ 8 yr | Pectus deformity | Growth and musculoskeletal features | 5/204 (2.45%) | 48/450 (10.67%) | 0.21 [0.06–0.54] | < 0.001 (Other) |
All | Congenital heart disease | Cardiovascular abnormalities | 18/363 (4.96%) | 108/964 (11.20%) | 0.41 [0.23–0.70] | < 0.001 (Other) |
