Table 1.
Clinical features of derivation cohort cases with Pathogenic/Likely Pathogenic NF1 or SPRED1 Variants
| ID | 1 | 2 | 3 | 4 | 5 | 6 |
|---|---|---|---|---|---|---|
| Age | 5Y | 1Y | 7Y | 2Y | 10M | 9Y |
| Sex | M | F | M | F | M | M |
| Gene | NF1 | NF1 | NF1 | NF1 | NF1 | SPRED1 |
| cDNA change | c.2033_2034insC | c.3357delA | c.3827G>A | c.5488C>T | c.(?_−50)_(*, *68_?)del | c.1A>G |
| Amino acid change | p.(Ile679Aspfs*, *21) | p.(Val1120Leufs*, *22) | p.(Arg1276Gln) | p.(Arg1830Cys) | Whole gene deletion | p.(Met1?) |
| Classification | Pathogenic | Likely Pathogenic | Pathogenic | Pathogenic | Pathogenic | Likely Pathogenic |
| Clinical Diagnosis/Suspicion | NSML | NFNS or NSML | NS | Unspecified | NFNS | Unspecified |
| Skin | ||||||
| Café au lait spots (n) | Y (multiple) | Y (multiple) | Y | Y | Skin findings, unspecified | Y (multiple) |
| Lentigines | N | Y | N | N | N | N |
|
Inguinal/ Axillary freckling |
N | Y | N | N | N | Y |
| Lisch Nodules | N | N | N | N | N | N |
| Wide‐spaced nipples | N | Y | N | N | N | N |
| Heart defect | ||||||
| Pulmonic valve stenosis | N | N | N | Y | Y | Y |
| Other | HCM | N | N | N | N | N |
| Facial Dysmorphism | ||||||
| Epicanthal Folds | N | Y | N | Y | Y | N |
| Ptosis | N | N | N | N | Y | N |
| Low Nasal Bridge | N | N | N | N | Y | N |
| Macrocephaly | N | N | N | N | N | N |
| Hypertelorism | Y | Y | N | N | Y | Y |
| Downward eye slant | Y | N | N | N | Y | Y |
|
Low set/ posteriorly rotated ears |
N | N | N | N | Y | N |
| Papillomas | N | N | N | N | N | N |
| Coarseness | N | N | N | N | N | N |
| Short/Thick neck | N | N | N | N | N | N |
| Short Stature | N | N | N | N | Y (10%ile) | N |
| Neurological Features | ||||||
| Developmental Delay | N | Y | N | N | Y | N |
| Learning Disabilities | N | N | N | N | N | Y |
| ID | N | N | N | N | N | N |
| Seizures | N | N | N | N | N | N |
| Skeletal Features | ||||||
| Pectus excavatum | N | Y | N | N | N | N |
| Pectus carinatum | N | N | N | N | N | N |
| Scoliosis | N | N | N | N | N | N |
| Neurofibromas | N | N | N | N | N | N |
| Other | N | Broad nasal root and tip, prominent forehead, scaphocephaly | Hypospadias | N | N | N |
| Family History | N | N | N | N | N | N |
*
Transcripts: NF1 (NM_000267.3) and SPRED1 (NM_152594.3)