Table 1. Clinical features and details of pathogenic NFIX deletions and sequence variants in Patients 1–6.
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | |
|---|---|---|---|---|---|---|
| Mechanism | Deletion | Deletion | Deletion | Deletion | Frameshift variant | Nonsense variant |
| Genes deleted/affected | NFIX | NFIX+CACNA1Aa | NFIX+CACNA1Aa | NFIX+CACNA1Aa | NFIX | NFIX |
| Minimal breakpoints/variant | 13 097 782_13 209 504 | 12 724 476_13 511 059 | 13 097 782_13 511 059 | 12 812 594_13 376 997 | c.90_99del, p.(Trp30fs) | c.1012C>T, p.(Gln338a) |
| Size | 110–170 kb | 740–810 kb | 410–470kb | 560–640kb | − | − |
| Age at last assessment | 10.0 years | 3.5 years | 2.7 years | 5.5 years | 5 years | 3 years |
| Birthweight (SD) | −1.3 | N/A | +0.5 | +1.1 | N/A | −0.25 |
| Length/height (SD)b | +2.2 | +1.0 | +0.5 | +2.8 | +2-3 | +0.7 |
| Weight (SD)b | +1.7 | +1.0 | +1.3 | +2.9 | +2.3 | 0 |
| OFC (SD)b | +0.7 | +0.7 | +1.6 | +3.9 | +3.3 | +1.0 |
| Dysmorphic features | Plagiocephaly, prominent forehead, facial asymmetry, low posterior hairline | Scaphocephaly, prominent forehead, depressed nasal bridge, deep-set eyes, high arched palate | Prominent forehead, slightly downslanting palpebral fissures | Scaphocephaly, prominent forehead | Prominent forehead, slightly downslanting palpebral fissures, elongated face, small mouth, pointed chin | Frontal bossing, mild facial asymmetry, slightly downslanting palpebral fissures |
| Developmental delay | Moderate | Moderate | Moderate | Severe | Severe | Severe |
| Neonatal feeding difficulties/hypotonia | − | − | − | − | − | − |
| Seizures | + | − | − | − | − | − |
| Episodic ataxia | − | − | − | − | − | − |
| Migraine | − | − | − | + | − | − |
| Nystagmus | − | + | − | − | − | − |
| Strabismus | − | + | + | + | + | + |
| Optic disc pallor/hypoplasia | − | − | − | − | − | − |
| Advanced bone age | − | N/A | N/A | N/A | + | N/A |
| Scoliosis | + | − | − | − | − | − |
| Pectus excavatum | + | + | + | − | + | − |
Abbreviations: OFC, occipital-frontal circumference; N/A, not available; SD, standard deviations above (+) or below (−) mean.
a
Also deleted in all cases are five annotated genes with no known human phenotype located between NFIX and CANCA1A (LYL1, TRMT1, NACC1, STX10 and IER2). Genomic positions are given according to build HG19.
b
Measurement at last assessment in clinic.