Table 1.
Clinical Features of Affected Individuals with Recessive DYNC1I2 Variants
| Family ID | Family 1 (F157) | Family 2 | Family 3 | ||
|---|---|---|---|---|---|
| Variation in DYNC1I2 (GenBank:NM_001378.2and NP_001369.1) | Allele 1: c.607+1G>A, Allele 2: c.607+1G>A | Allele 1: c.740A>G (p.Tyr247Cys), Allele 2: 374 kb deletion at 2q31.1 | Allele 1: c.740A>G; (p.Tyr247Cys), Allele 2: c.868C>T; (p.Gln290∗) | ||
| Origin | Pakistani | Russian/Polish/Austrian/Ashkenazi Jewish/Irish/Swedish/German | Polish, Russian | ||
| Individual ID | 1-VI:1 | 1-VI:2 | 1-VI:3 | 2-II:1 | 3-II:1 |
| Sex | male | female | female | male | female |
| Age at last evaluation (years) | 20 | 32 | 34 | 3 | 8 months |
| Height (cm) | 156 | 152 | 145 | 90 | 61 |
| Head circumference (cm) | 47 (<1st percentile) | 48 (<1st percentile) | 48 (<1st percentile) | 41.8 (<1st percentile) | 35 (<1st percentile) |
| Intellectual disability | severe | severe | severe | yes | yes |
| Developmental delay | yes | yes | yes | yes | yes |
| Speech | delayed | delayed | delayed | delayed | delayed |
| Motor milestones | delayed | delayed | delayed | delayed | delayed |
| Behavioral problems | ADHD, aggressive | ADHD, aggressive | ADHD, aggressive | unknown | unknown |
| Facial dysmorphism | yes | yes | yes | yes | yes |
| Brain MRI | Microcephaly with simplified gyral pattern, near complete agenesis of corpus callosum with colpocephaly, and mild brain atrophy | not done | not done | Microcephaly with simplified gyral pattern, mega-cisterna magna, absence of the rostrum and genu of the corpus callosum and the septum pellucidum, and partial absence of the splenium. | Microcephaly with simplified gyral pattern, hypogenesis of the corpus callosum—small genu and splenium, reduced white matter volume, ventricle abnormality—and large trigones |
| Other symptoms | N/A | N/A | N/A | Seizures, multiple hemangiomas | Seizures, hypothyroidism, gastresophageal reflux, joint hyperextensibility, and unilateral hearing loss due to left cochlear defect |
Abbreviations are as follows: hom = homozygous; ADHD = Attention deficit hyperactivity disorder, and MRI = magnetic resonance imaging.