Table 4.
Genotype–phenotype correlations in this series and patients of the literature.
| Missense SNV | CNV (and truncating varianta) | ||||||
|---|---|---|---|---|---|---|---|
| Patient/article | Patients study 1–6 | Mathijssen et al. [19] | Total missense SNV | Patients study 7–14 | Molin et al. [9] | Total CNV and truncating variant | p value SNV/CNV and truncating variant (Fisher’s test) |
| Dalal et al. [6] | Vuillaume et al. [20] | ||||||
| Carvalho et al. [21] | Lowther et al. [18] | ||||||
| Posmyk et al. [22] | Quintela et al. [23] | ||||||
| Mattioli et al. [8] | |||||||
| Casertano et al. [14] | |||||||
| Alby et al. [13] | |||||||
| Stellacci et al. [24] | |||||||
| Grímsdóttir et al. [25] | |||||||
| Cleaver et al. [26] | |||||||
| General | |||||||
| Number of patients | 6 | 17 | 23 | 8 | 26 | 34 | |
| M/F | 2/4 | 10/7 | 12/11 | 6/2 | 14/12 | 20/14 | p = NS |
| Mean age (years) | 14.5 | 15.4 | 15.1 | 11.6 | 8.7 | 9.4 | p = NS |
| Extreme ages (years) | (2–40) | (1.5–43) | (1.5–43) | (3–38) | (0–41) | (0–41) | |
| Measurement | |||||||
| Birth weight > +2 SD | 0/5 | 1/15 | 1/20 (5%) | 0/8 | 0/18 | 0/26 (0%) | p = NS |
| Birth length > +2 SD | 1/5 | 2/11 | 3/16 (18.8%) | 0/8 | 1/13 | 1/21 (4.8%) | p = NS |
| Birth OFC > +2 SD | 3/5 | 4/10 | 7/15 (46.7%) | 1/8 | 4/11 | 5/19 (26.3%) | p = NS |
| Last weight > +2 SD | 0/5 | 4/16 | 4/21 (19%) | 2/7 | 6/20 | 8/27 (29.6%) | p = NS |
| Last length > +2 SD | 0/6 | 2/17 | 2/23 (8.7%) | 3/8 | 6/21 | 9/29 (31.0%) | p = NS |
| Last OFC > +2 SD | 4/5 | 10/17 | 14/22 (63.6%) | 3/8 | 7/20 | 10/28 (39.7%) | p = NS |
| Neurological | |||||||
| Developmental delay/ID | 6/6 | 17/17 | 23/23 (100%) | 8/8 | 21/21 | 29/29 (100%) | p = NS |
| Language delay | 6/6 | 17/17 | 23/23 (100%) | 8/8 | 17/19 | 25/27 (92.6%) | p = NS |
| Behavioral disorder | 1/6 | 7/17 | 8/23 (34.8%) | 3/8 | 2/3 | 5/11 (45.5%) | p = NS |
| Ataxia | 2/6 | 0/17 | 2/23 (8.7%) | 1/8 | 1/3 | 2/11 (18.2%) | p = NS |
| Epilepsy | 0/6 | 0/17 | 0/23 (0%) | 0/8 | 2/26 | 2/34 (5.9%) | p = NS |
| Corpus callosum anomalies | 5/6 | 14/17 | 19/23 (82.6%) | 2/8 | 7/26 | 9/34 (26.5%) | p = 0.00004 |
| Ventriculomegaly | 3/6 | 1/17 | 4/23 (17.4%) | 0/8 | 3/26 | 3/34 (8.8%) | p = NS |
| Cerebral calcification | 0/NA | 3/NA | NA | 0/8 | 0/26 | 0/34 (0%) | NA |
| Anxiety | 2/6 | 1/17 | 3/23 (13%) | 4/8 | 1/3 | 5/11 (45.5%) | p = NS |
| Motor stereotypies | 4/6 | 1/17 | 5/23 (21.7%) | 4/8 | 1/3 | 5/11 (45.5%) | p = NS |
| Autism | 0/6 | 2/17 | 2/23 (8.7%) | 1/8 | 4/26 | 5/34 (14.7%) | p = NS |
| ADHD | 0/6 | 1/17 | 1/23 (4.3%) | 0/8 | 6/26 | 6/34 (17.6%) | p = NS |
| Schizophrenia | 1/6 | 0/17 | 1/23 (4.3%) | 0/8 | 1/26 | 1/34 (2.9%) | p = NS |
| Sleep disturbances | 0/6 | 1/17 | 1/23 (4.3%) | 1/8 | 1/3 | 2/11 (18.2%) | p = NS |
| Facial features | |||||||
| Skull malformation | 0/6 | 3/17 | 3/23 (13%) | 3/8 | 7/26 | 10/34 (29.4%) | p = NS |
| Hypertelorism | 0/6 | 2/17 | 2/23 (8.7%) | 0/8 | 8/17 | 8/25 (32%) | p = NS |
| Prominent forehead | 3/6 | 8/17 | 11/23 (47.8%) | 2/8 | 10/14 | 12/22 (54.5%) | p = NS |
| Strabismus | 3/6 | 4/17 | 7/23 (30,4%) | 0/8 | 6/15 | 6/23 (26.1%) | p = NS |
| Downslanting palpebral fissures | 4/6 | 9/17 | 13/23 (56.5%) | 5/8 | 7/13 | 12/21 (57.1%) | p = NS |
| Ptosis | 2/6 | 5/17 | 7/23 (30.4%) | 1/8 | 5/11 | 6/19 (31.6%) | p = NS |
| Epicanthus | 5/6 | 4/17 | 9/23 (39.1%) | 2/8 | 9/15 | 11/23 (47.8%) | p = NS |
| Larges ears | 4/6 | 0/17 | 4/23 (17.4%) | 1/8 | 5/15 | 6/23 (26.1%) | p = NS |
| Depressed nasal bridge | 0/6 | 5/17 | 5/23 (21.7%) | 1/8 | 0/4 | 1/12 (8.3%) | p = NS |
| Broad nasal bridge | 0/6 | 6/17 | 6/23 (26.1%) | 0/8 | 2/13 | 2/21 (9.5%) | p = NS |
| Anteverted nares | 2/6 | 2/17 | 4/23 (17.4%) | 2/8 | 3/10 | 5/18 (27.8%) | p = NS |
| Downturned corners of the mouth | 2/6 | 4/17 | 6/23 (26.1%) | 1/8 | ND | 1/8 (12.5%) | p = NS |
| Small mouth | 3/6 | 4/11 | 7/17 (41.2%) | 0/8 | ND | 0/8 (0%) | p = NS |
| High-arched palate | 1/6 | 3/17 | 4/23 (17.4%) | 0/8 | ND | 0/8 (0%) | p = NS |
| Micrognathia/retrognathia | 0/6 | 2/17 | 2/23 (8.7%) | 2/8 | ND | 2/8 (25%) | p = NS |
| Muscular | |||||||
| Hypotonia | 5/6 | 10/17 | 15/23 (65.2%) | 6/8 | 14/18 | 20/26 (76.9%) | p = NS |
| Muscle wasting | 1/6 | 5/17 | 6/23 (26.1%) | 0/8 | 0/2 | 0/10 (0%) | p = NS |
| Muscle contractures | 1/6 | 4/17 | 5/23 (21.7%) | 0/8 | ND | 0/8 (0%) | p = NS |
| Sensory | |||||||
| Bilateral hearing loss (perceptive or mixed) | 5/6 | 13/17 | 18/23 (78.3%) | 1/8 | ND | 1/8 (12.5%) | p = 0.002 |
| Cataract | 0/6 | 1/17 | 1/23 (4.3%) | 0/8 | 1/25 | 1/33 (3%) | p = NS |
| Calcification of the external auditory canal | 0/6 | 1/17 | 1/23 (4.3%) | 0/8 | ND | 0/8 (0%) | NA |
| Orthopedic | |||||||
| Ossification delay | 3/3 | 3/NA | NA | NA | NA | NA | NA |
| Joint hyperlaxity | 3/6 | 3/17 | 6/23 (26.1%) | 3/8 | 1/24 | 4/32 (12.5%) | p = NS |
| Knee deformation | 2/6 | 2/17 | 4/23 (17.4%) | 3/8 | 0/24 | 3/32 (9.4%) | p = NS |
| Hip dysplasia | 0/6 | 1/17 | 1/23 (4.3%) | 0/8 | 1/24 | 1/32 (3.1%) | p = NS |
| Spine deformation | 1/6 | 5/17 | 6/23 (26.1%) | 2/8 | 5/24 | 7/32 (21.9%) | p = NS |
| Long fingers | 1/6 | 0/17 | 1/23 (4.3%) | 0/8 | 2/24 | 2/32 (6.3%) | p = NS |
| Feet deformation | 3/6 | 2/17 | 5/23 (21.7%) | 2/8 | 7/24 | 9/32 (28.1%) | p = NS |
| Total skeletal malformation | 5/6 | 10/17 | 15/23 (65.2%) | 4/8 | 14/24 | 18/32 (56.3%) | p = NS |
| Endocrinology | |||||||
| Hypothyroidism | 2/6 | 3/17 | 5/23 (21.7%) | 0/8 | 1/23 | 1/31 (3.2%) | p = 0.047 |
| Diabetes mellitus | 0/6 | 2/14 | 2/20 (10%) | 0/8 | 1/23 | 1/31 (3.2%) | p = NS |
| Delayed puberty | 1/2 | 0/6 | 1/8 (12.5%) | 1/3 | ND | 1/3 (33.3%) | p = NS |
| Others | |||||||
| Pinnae calcification | 2/NA | 3/NA | NA | NA | NA | NA | NA |
| Inguinal hernia (males) | 0/2 | 3/10 | 3/12 (25%) | 1/6 | 10/17 | 11/23 (47.8%) | p = NS |
| Congenital cardiopathy | 1/6 | 3/17 | 4/23 (17.4%) | 1/8 | 2/26 | 3/34 (8.8%) | p = NS |
ND no data, NC not concerned, NS not significant.
aOnly one truncating SNV.