Table 1.
Clinical and molecular data of ITSN1 patients (NM_003024.2).
| Present reported cases | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | Patient 7 | Patient 8 | Patient 9 | Patient 10 | |
| Country | France | USA | USA | USA | Danmark | Canada | USA | USA | USA | USA |
| Sex | M | M | M | M | M | M | M | M | M | F |
| Age at last examination | 27 years 7months | 18 years | 3 years | 14 years | 10 years 1 month | 7 years | 6 years | 2 years 6 months | 7 years 5 months | 4 years 9 months |
| Weight | −0.5 SD | +0.3 SD | +2 SD | NA | +1 SD | <−2 SD | +2.5 SD | +1.5 SD | −0.2 SD | +0.79 SD |
| Height | +3.62 SD | −2 SD | +1.7 SD | NA | −1.5 SD | <−2 SD | +2 SD | +0.2 SD | 0 SD | +1.73 SD |
| OFC | +1.4 SD | 0 SD | 0 SD | NA | NA | −2 SD | +0.5 SD | +2.5 SD | +2 DS | NA |
| Cranio-facial features | Preauricular skin tag [HP:0000384], everted lower lip vermilion [HP:0000232], prominent nose [HP:0000448], prominent maxilla [HP:0430028] | Brachycephaly [HP:0000248], thickened helices [HP:0000391], epicanthus [HP:0000286], everted lower lip vermilion [HP:0000232] | Mild dolichocephaly [HP:0000268], broad forehead [HP:0000337], epicanthus [HP:0000286] | − | − | Microcephaly [HP:0000252], epicanthus [HP:0000286], prominent nose [HP:0000448], smooth philtrum [HP:0000319], thin upper vermillion [HP:0011339], micrognathia [HP:0000347] | Mild hypertelorism [HP:0000316], epicanthus [HP:0000286], wide mouth [HP:0000154], Widely spaced teeth [HP:0000687] | Macrocephaly [HP:0000256], High forehead [HP:0000348], epicanthus [HP:0000286] | High forehead [HP:0000348] | |
| Ocular anomalies | Cataract [HP:0000518], strabismus [HP:0000486] | Refractive error | NA | − | NA | Hypermetropia [HP:0000540], astigmatism [HP:0000483], | − | − | Hypermetropia [HP:0000540], astigmatism [HP:0000483], amblyopia [HP:0000646], accomodative esotropia [HP:0031764] | − |
| Hearing impairment [HP:0000365] | − | + | NA | − | − | − | − | − | − | − |
| Musculo-skeletal features | pes planus [HP:0001763], joint laxity [HP:0001388], arachnodactyly [HP:0001166], slender build [HP:0001533] | Pes cavus [HP:0001761], bilateral Hammertoe [HP:0001765] | Overlapping toe [HP:0001845] | − | − | Short stature [HP:0004322], brachydactyly [HP:0001156], single transverse palmar crease [HP:0000954] | − | Pes planus [HP:0001763] | Bilateral clinodactyly [HP:0030084] | − |
| Cardiac features | − | Syncopes [HP:0001279], | NA | − | − | − | − | − | − | − |
| Gastro-intestinal anomalies | Constipation [HP:0002019] | Constipation [HP:0002019], gastroesophageal reflux [HP:0002020], | NA | − | − | Gastroesophageal reflux [HP:0002020] | Diarrhea frequent in infancy [HP:0002014] | − | − | − |
| Other features | Striae extensae, Medullary thyroid carcinoma [HP:0002865], Episodic hypokalemia [HP:0012726], potomania | Eczema [HP:0000964], gynecomastia [HP:0000771], asthma [HP:0002099] | inguinal hernia [HP:0000023] Hydrocele [HP:4000037] | Sensitive gag reflex, Hydrocele [HP:4000037], Inguinal hernia [HP:0000023] | − | Eczema [HP:0000964] | - | Right undescended testicle, right inguinal hernia [HP:0000023], burried penis, phimosis [HP:0001741], Feeding difficulties [HP:0011968] | Café-au-lait spots, obstructive sleep apnea [HP:0002870] | Frequent ear infections, feeding difficulties [HP:0011968] |
| Global developmental delay [HP:0001263] | + | + | + | + | + | + | + | + | + | + |
| Intellectual disability (IQ test) [HP:0001249] | Mild (NA) | Mild (69) | NA | Mild (61) | Mild (67) | − | Mild-Moderate | NA | NA | NA |
| Autistic behavior [HP:0000729] | + | + | + | + | + | − | + | + | + | + |
| Delayed speech and language development [HP:0000750] | + | + | + | + | + | + | + | + | + | + |
| Echolalia [HP:0010529] | + | − | NA | + | NA | − | NA | NA | + | + |
| Speech apraxia [HP:0011098] | NA | + | NA | + | + | + | NA | NA | NA | NA |
| Seizure (age at onset) [HP:0001250] | + (12 years) | − | − | − | + (1 year 6 months) | − | − | − | + | − |
| Behavioral abnormality[HP:0000708] | Bulimia, anorexia, self-mutilation, anxiety, ADHD, stereotypies, aggressivity | ADHD | Poor socialization, repetitive behaviors | ADHD, anxiety, motor tics disorder | Stereotypies, social interaction problems | Impulsivity, aggressive behavior, ADHD, social difficulties | NA | − | ADHD | Tantrums |
| Gait disturbance [HP:0001288] | NA | + | − | − | − | − | NA | − | − | − |
| Hypotonia [HP:0001252] | + | + | + | + | − | − | + | − | − | − |
| Sleep disturbance [HP:0002360] | − | − | − | − | NA | − | NA | − | + | − |
| Psychiatric disorder | + | NA | NA | Very early onset psychosis | − | NA | NA | − | − | − |
| Brain MRI anomalies | − | − | NA | − | − | Prominent perivascular spaces, high signal white matter, slow myelination | Delayed myelinization, gliosis | − | NA | NA |
| Variant | chr21:g.35169690 C > T | chr21::g.35190737dupA | chr21:g.35138177 A > G | chr21:g.35154339 G > T | chr21: g.35254559 A > T | chr21:g.35144580 G > T | chr21:g.35147116_35147119delAGAA | chr21:g.35195890 G > A | chr21:g.35195890 G > A | chr21:g.35195890 G > A |
| c.1960C > T | c.2894dupA | c.789-2 A > G | c.1726G > T | c.4354 A > T | c.1258 G > T | c.1389_1392delAGAA | c.3116 G > A | c.3116 G > A | c.3116 G > A | |
| p.(Gln654*) | p.(Tyr965*) | p.? | p.(Glu576*) | p.(Asn1452Tyr) | p.(Glu420*) | p.(Lys463Asn*5) | p.(Trp1039*) | p.(Trp1039*) | p.(Trp1039*) | |
| PolyPhen-2 | NA | NA | NA | NA | 0.952 | NA | NA | NA | NA | NA |
| CADD | 38 | NA | NA | 39 | 29 | NA | NA | 40 | 40 | 40 |
| GnomAD frequency | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 | 0.00 |
| Inheritance | de novo | NA (adopted) | de novo | Inherited from father | de novo | NA (adopted) | NA | Inherited from father | Inherited from father | Inherited from father |
NA not available, ADHD attention-deficit hyperactivity disorder, MRI magnetic resonance imaging, OFC occipitofrontal circumference, HPO number are noted [HP].