Table 2.
Clinical Features in Indifviduals with NFIB Haploinsufficiency (Deletions)
| Subject | P8a | P8b | P9 | P10a | P10b | P11 | P12 | P13 | P14 | P15 | Summary All Subjects |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Aberration | 9p23p22.3 (14098659_14324147)x1 | 9p23p22.3 (14098659_14324147)x1 | 9p22.3p23 (14102175_14386038)x1 | 9p23p22.3 (13974415_14286259)x1 | 9p23p22.3 (13974415_14286259)x1 | 9p23p22.3 (13106806_14639971)x1 | 9p23p22.3 (13034407_14653394)x1 | 9p23p22.2 (14178768_16619009)x1 | 9p23p22.2 (13563537_18491752)x1 | 9p23p22.2 (13739630_18023839)x1 | |
| Deletion size | 225 kb | 225 kb | 284 kb | 312 kb | 312 kb | 1.5 Mb | 1.6 Mb | 2.4 Mb | 4.9 Mb | 4.3 Mb | |
| Inheritance | familial | familial | de novo | de novo | maternally inherited | de novo | unknown | de novo | de novo | de novo | |
| Sex | F | F | M | F | F | M | M | F | M | F | |
| Age at last examination | 6 y | 8 y | 7 y | 20 y | 3 y 5 m | 8 y 4 m | 21 y | 7 y 10 m | 10 y | 17 y | |
| Prenatal Growth >2 SDS | |||||||||||
| Birth weight (g) (SD) | ND | 3,470 (−0.1 SD; 54th) | 3,500 (−0.10 SD; 46th) | 4,400 (+2.13 SD; 98th) | 3,400 (−0.05 SD;48th) | 2,750 (−1.30 SD; 10th) | ND | 4,030 (+1.32 SD; 91th) | 3,200 (−0.58 SD; 28th) | 3,370 (−0.11 SD; 46th) | 1/16 |
| Body length at birth (cm) (SD) | ND | ND | 50 (−0.06 SD; 48th) | 58 (+3.1 SD; > 99th) | ND | 49 (−0.44 SD; 33th) | ND | 56 (+2.38 SD; 99th) | 49 (−0.44 SD; 33th) | ND | 2/7 |
| OFC (cm) (centile) | ND | ND | 37 (+0.68 SD; 75th) | 39 (+1.92 SD; 97th) | 37 (+1.22SD; 89th) | 34 (−0.83 SD; 20th) | ND | 37 (+1.22 SD; 89th) | ND | ND | 1/8 |
| Postnatal Growth >2 SDS | |||||||||||
| Height (cm) (SD) | 122.6 (+1.46 SD; 93th) | 131 (+0.56 SD; 71th) | 131 (+1.70 SD; 96th) | 165 (+0.27 SD; 61th) | 92 (−0.68 SD; 25th) | 131.5 (+0.62 SD; 73th) | 177.8 (−0.17 SD; 57th) | 137 (+2.68 SD; >99th) | 144 (+0.80 SD; 79th) | (75 centile) | 3/16 |
| Weight (kg) | 26.2 (+1.32 SD; 91th) | 28.9 (+0.49 SD; 69th) | 22 (−0.41 SD; 34th) | 68.5 (+0.68 SD; 75th) | 18.9 (+2.36 SD; 99th) | 25.5 (−0.04 SD; 48th) | ND | 43.9 (+3.82 SD; >99th) | 41 (+0.99 SD; 84th) | (50–75 centile) | 3/15 |
| OFC (cm) (SD) | 55.6 (+3.35 SD; >99th) | 55.2 (+2.71 SD; >99th) | 55 (+2.17 SD; 99th) | 61 (+6.01; >99th) | 55.5 (+4.60 SD; >99th) | 52.5 (+0.15 SD; 56th) | 61.5 (+4.46 SD; >99th) | 57 (+4.39 SD; >99th) | 54.5 (+1.19 SD; 88th) | (50–75 centile) | 13/16 |
| Neurodevelopmental Characteristics | |||||||||||
| Muscular hypotonia | N | N | Y | Y | Y | N | N | Y | Y | Y | 11/17 |
| Motor delay | ND | ND | Y | Y | Y | N | Y | N | Y | N | 11/16 |
| Speech delay | Y | Y | Y | Y | Y | Y | Y | Y | Y | Y | 18/18 |
| Intellectual disability | learning disability (not formally tested) | borderline mild ID | learning disability | mild | mild | mild | learning disability | mild | mild | learning disability | 18/18 |
| Attention deficit | Y | Y | Y | Y | NA | Y | Y | Y | Y | Y | 11/15 |
| Behavioral anomalies | reactive attachment disorder, passive, pleasing | autistic features, social difficulties | N | short temper | NA | anxiety, hetero-agressivity | ASD, impulse control problems, trouble gauging emotions | Y | ASD and psychotic episodes | Y | 13/15 |
| Seizures | N | N | N | N | N | N | N | N | N | N | 0/18 |
| Neurological deficits | N | N | N | ND | ND | N | insensitivity to pain, temperature dysregulation | N | N | N | 2/14 |
| Brain MRI Findings | 9/11 | ||||||||||
| Corpus callosum anomaly | ND | N | N | ND | ND | ND | complete agenesis | complete agenesis | N | ND | 5/11 |
| Ventriculomegaly | ND | N | N | ND | ND | ND | Y | N | N | ND | 2/11 |
| Other | ND | slight asymmetric hemispheres | NA | ND | ND | ND | moderately decreased white matter volume; bilateral probst bundles | mildely decreased white matter volume | NA | ND | 7/11 |
| Internal Malformations | 7/17 | ||||||||||
| Genitourinary system | N | N | N | N | N | ND | N | N | cryptorchidism | N | 2/17 |
| Gastrointestinal system | N | N | N | N | N | ND | N | N | N | N | 0/17 |
| Heart | small VSD | narrow pulmonary artery, normalized at 2 y | N | N | PDA | ND | N | N | N | bicuspid aortic valve | 5/17 |
| Other malformations | N | N | N | N | N | NA | N | N | N | N | 0/17 |
Abbreviations: Y, trait present; N, trait absent; ND, not determined; NA, not applicable; ID, intellectual disability; SD, standard deviation; gw, weeks of gestation.