Table 1.
Patients’ clinical and genetic characteristics. Patient 7 is the mother of patient 6. Patient 9 and 11 are not related.
| Patient # | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Variant | (15291644_15388348)x1 | (15330889_15419256)x1 | (15374392_15405436)x1 | c.2866dupG p.(Glu956GlyfsTer72) | c.2731 + 1G > C | (15383717_15462037)x1 | (15383717_15462037)x1 | deletion exons 6-18 * | c.2363G > A p.(Arg788Gln) | c.1930G > A p.(Glu644Lys) | c.2363G > A p.(Arg788Gln) |
| Genomic position (hg19) | - | - | - | (15511546dup) | (15507648G > C) | - | - | - | (15501555G > A) | (15497386G > A) | (15501555G > A) |
| Variant type | Del | Del | Del | FS | SS | Del | Del | Del | Mis | Mis | Mis |
| Inheritance | dn | dn | dn | dn | dn | mat | NA | dn | dn | dn | mat † |
| Classification | P | P | P | P | LP | P | P | P | VUS | VUS | VUS |
| Gender | M | F | F | M | M | F | F | M | F | M | M |
| Age (years) | 14 | 21 | 18 | 14 | 5 | 6 | 36 | 9 | 43 | 12 | 8 |
| Intellectual functioning | Mild ID (IQ 61-74) | Borderline intellectual functioning (IQ 82) | Mild ID (IQ 50) | Moderate ID(IQ NA) | IQ NA | Normal | Learning difficulties (IQ NA) | Mild ID (IQ NA) | Learning difficulties (IQ 79) | Mild ID (IQ 66) | Normal |
| Developmental delay | + | + | + | + | + | + | + | + | + | + | + |
| Behavior abnormalities | - | + | - | + | - | - | - | + | + | - | - |
| Autistic features | + | - | + | + | - | - | - | + | + | - | - |
| ASD diagnosis | - | - | - | + | - | - | - | + | + | - | - |
| Hypotonia | - | - | - | - | + | - | - | + (mild) | - | - | + (later spasticity) |
| Gait disturbance | - | - | - | - | - | + (previously rigid walking pattern) | - | + | - | - | + (due to spasticity) |
| MRI abnormalities | NA | NA | NA | Small posterior fossa cyst or mega cisterna magna | Arachnoid cyst | NA | NA | Normal spinal cord MRI | NA | NA | Brain MRI: lack of myelinization. Normal spinal MRI. |
| Dysmorphic features | |||||||||||
| - Broad forehead | + | - | - | - | + | - | - | + | - | - | + |
| - High anterior hair line | - | + | + | + | - | + | - | + | - | - | + |
| - Prominent supraorbital ridges | - | - | - | - | - | - | - | + | - | - | - |
| - Deeply set eyes | - | + | + | - | + | - | - | + | - | - | + |
| - Infraorbital dark circles | + | - | + | - | - | + | - | + | - | - | + |
| - Midface hypoplasia | - | + | - | - | - | - | - | - | - | - | + |
| - Depressed nasal bridge | - | - | + | - | - | - | - | slight | - | - | - |
| - Bulbous nasal tip | - | - | + | - | - | + | + | - | - | - | + |
| - Short philtrum | - | + | + | + | - | - | - | - | - | - | + |
| - Full lips | - | - | + | + | - | - | - | - | - | - | + |
| Other anomalies | Pes plano valgus, mild hypermetropia | Submucous cleft palate, bifid uvula | Fetal finger pads, slight tapering of digit II and V bilateral. | 2 café au lait macules | Right cryptorchidism, congenital torticollis | Supernumerary tooth | - | Kyfoscoliosis, bladder spasticity | Strabismus convergens, camptodactyly digiti V of the hands, syndactyly dig 2–3 of the feet | Severe global spasticity, neurogenic bladder |
Variants based on NM_004973.4. Del; Deletion, FS; Frameshift, SS; Splice site, Mis; missense, dn; de novo, mat; maternal, LP; likely pathogenic, P; pathogenic, VUS; variant of unknown significance, F; Female, M; Male, ID; intellectual disability, ASD; autism spectrum disorder, NA; not assessed, -; absent, +; present. Patient 1, 2, 3, 4, 6 and 7 are analyzed with array techniques and the notation arr[GRCH37]6p22.3 is used. * Exact position is not known. † Mother apparently unaffected.