Table 1 Medical and neurodevelopmental features of individuals with CAS and pathogenic/likely pathogenic variants.
Family | Age, y;m | Sex | Core speech phenotype | Gene | Gross motor delay | Fine motor delay | Vision impaired | Hearing loss | MRI findings | Seizures | Other NDD | Dysmorphic features | Other medical | |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
1 | 16;8 | F | CAS | ARHGEF9 | Y | Y | Y | N | Small pineal cyst | Y | Mild ID, ASD | Clinodactyly 5th fingers*, severe class 3 malocclusion *with lateralisation of the mandible to the left | Prognathism and clinodactyly reported features | Cow milk allergy; selective IgA deficiency; polycystic ovaries; fibrous dysplasia of skull and jaw |
2 | 5;6 | F | Dysarthria | DDX3X | Y | Y | N | N | N | N | Mild ID, ASD, DCD | Upturned nose*, thin upper lip*, broad nasal tip*, small midface epicanthic folds | Gut inflammation, bowel issues, sleep disturbances | |
3 | 6;0 | F | CAS | KDM5C | N | N | N | N | Hypoplastic cerebellar vermis and brainstem, possibly decreased volume of white matter, dysmorphic corpus callosum and hypoplastic hippocampi | N | Mild ID | Downslanting palpebral fissures*, low columella*, hypoplastic alae nasi | Severe allergic rhinitis with development of Harrisons sulci, tonsillectomy, adenoidectomy, obstructive sleep apnoea, grommets | |
4 | 7;4 | M | CAS | PHF21A | Y | Y | N | N | N | N | Mild ID, attention difficulties, executive functioning difficulties | Hypoplasia of nasal septum, downturned corners of mouth*, supraorbital fullness*, smiling absent* | Eczema, adenoidectomy | |
5 | 3;2 | M | Inconsistent phonological delay and disorder | BRPF1 | Y | N | N | N | N | N | N | Periorbital fullness*, retrognathia, small cupped ears, thin lips, fine eyebrows, flat philtrum, downslanted palpebral fissures* | N | |
6 | 7;2 | F | Phonological disorder, articulation disorder | PURA | Y | Y | Glasses | N | N | N | Attention difficulties | Pointed chin,* long face* | Oropharyngeal dysmotility | |
7 | 4;8 | M | CAS | ZBTB18 | Y | Y | Glasses | N | N | N | Attention difficulties | Wide mouth, everted lower lip, small jaw | Viral induced asthma; eczema; moderate oral phase dysphagia | |
8 | 3;2 | F | CAS | HNRNPK | Y | Y | N | N | N | N | GDD | Slightly prominent forehead*, epicanthic folds, slightly broad nose* | Atrioventricular septal defect, hypotonia, grommets | |
9 | 5;9 | M | CAS, phonological disorder | SETD1A | Y | Y | N | N | N | N | Sensory difficulties | High forehead, high anterior hairline | Undescended testis, sleep disturbances | |
10 | 10;1 | M | CAS, phonological error patterns | SETD1B | Y | Y | Y | N | N | Y | N | Short philtrum*, anteverted ears*, prominent triangular nose*, small jaw | Low muscle tone, loose joints, short stature | |
11 | 4;3 | M | CAS, phonological error patterns | RBFOX3 | Y | Y | N | N | N | N | N | N | N | |
12 | 4;1 | M | CAS, phonological error patterns | TAOK2 | Y | Y | N | N | N | N | Mild ID, DCD | N | Collapsed lung | |
13 | 2;2 | M | CAS, minimally verbal | SPAST | Y | N | N | N | N | N | N | N | Spastic diplegia | |
14 | 3;7 | M | CAS, minimally verbal | SHANK3 | Y | Y | N | N | N | N | N | N | N | |
15 | 7;4 | M | CAS, phonological delay | DIP2C | Y | Y | N | N | N | N | N | N | N | |
16 | 3;11 | M | CAS | SETBP1 | Y | Y | N | N | N | N | Attention difficulties | Periorbital fullness*, broad nasal tip*, pointed chin | Motor dyspraxia, tongue tie (corrected) | |
17 | 4;6 | F | CAS, Dysarthria | TRIP12 | Y | Y | N | N | N/A | N | N | N | N | |
18 | 4;7 | M | CAS | ERF | N | N | N | N | CHIARI 1 Malformation Metopic craniosynostosis | N | N | N | N |
