Molecular and clinical data from the 17 patients with SYNGAP1 mutations*
| Patient ID | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 |
|---|---|---|---|---|---|---|---|---|---|
| Age at the time of the study (years) | 14 | 15 | 8.5 | 10.8 | 15 | 11 | 5 | 9.8 | 5.5 |
| Sex | M | F | F | M | F | M | F | F | F |
| Ancestry | Guinean | European | European | European | Moroccan | Malian | European | European | European |
| Genetics | |||||||||
| Mutation type | Intragenic deletion | Nonsense | Nonsense | Nonsense | Frameshift | Nonsense | Splice site | Frameshift | Frameshift |
| Mutation | c.68–1518-?_1530+?del | c.348C>A | c.403C>T | c.427C>T | c.455_459del | c.490C>T | c.509+1 G>T | c.828dup | c.1057delC |
| Protein level | p.? | p.Tyr116* | p.Arg135* | p.Arg143* | p.Arg152Glnfs*14 | p.Arg164* | p.? | p.Lys277Glnfs*7 | p.Leu353Trpfs*13 |
| Location in gene | Intron 1—exon 9 | Exon 4 | Exon 5 | Exon 5 | Exon 5 | Exon 5 | Intron 5 | Exon 8 | Exon 8 |
| Inheritance | De novo | De novo | De novo | De novo | De novo | De novo | De novo | Parents not tested | Parents not tested |
| Level of intellectual disability/age at evaluation | Severe/10 years | Mild/12 years | Moderate/5.5 years | Severe/10.8 years | Severe/11 years | Severe/11 years | Moderate/5 years | Moderate/4.5 years | Moderate/5.5 years |
|---|---|---|---|---|---|---|---|---|---|
| Developmental stages | |||||||||
| Age of sitting/walking | 7 months/24 months | 10 months/<18 months | 10 months/20 months | 10 months/24 months | 16 months/36 months | 8 months/20 months | 10 months/22 months | 9 months/15 months | NA/24 months |
| Age of first words/first sentences | 4 years/no sentences | 14 months/NA | 33 months/no sentences | 5 years (5 words)/no sentences | 4 years transient ‘mama’ ‘papa’/no sentences | NA/no sentences | 3 years/5 years | 23 months | 36 months/no sentences |
| Current language ability | Single words | NA | ∼50 words | 10 words | Absence of speech | Few words at 11 years | 5-word sentences | Short sentences | 15 words |
| Regressive episode during the development/age | Slowing of development with untreated epilepsy/2 years | No | No | No | Possible (loss of few acquired words) | No | Loss of few dissyllable words after 20 months | No | NA |
| Autism spectrum disorder | No | Yes | No | Yes | Yes | Yes | No | No | No |
| Clinical examination | |||||||||
| Age at examination | 14 years | 12 years | 5.5 years | 10.8 years | 11 years | 10 years | 5 years | 6 years | 5.5 years |
| Height in cm (SD)/weight in kg (SD)/head circumference in cm (SD) | 133 (−0.5)/28 (−0.5)/50.5 (−1) | 173 (+2.5)/40 (−1)/53 (−1) | 151 (+1)/53 (+3)/53.5 (−0.5) | NA | 156 (−0.75)/62 (+0.25)/NA | 143 (+4)/35 (+3.5)/51 (−0.5) | 15 (−1.5)/103 (−1.5)/49 (−1.5) | 105 (−0.5)/16 (−1)/52 (+0.5) | 110 (−1.5)/17.9 (−1.5)/50.5 (−0.5) |
| Neurological examination | Normal | Normal | Global hypotonia, gait ataxia | Truncal hypotonia | Nystagmus during the 1st year (possibly caused by myopia), clumsy gait | Facial and truncal hypotonia, broad-based gait | Truncal hypotonia | Facial hypotonia with drooling, gait ataxia | Truncal hypotonia, walking with inwards rotation of hips |
| Patient ID | 10 | 11 | 12 | 13 | 14 | 15 | 16 | 17 | Summary |
|---|---|---|---|---|---|---|---|---|---|
| Age at the time of the study (years) | 5 | 3 | 22 | 12 | 8 | 8.2 | 29 | 10 | Mean 11.4 |
| Sex | M | M | F | M | F | M | M | M | M=8, F=9 |
| Ancestry | European | Iraqi | European | Turkish | European | European | European | European | |
| Genetics | |||||||||
| Mutation type | Nonsense | Nonsense | Missense | Nonsense | Frameshift | Frameshift | Frameshift | Splice site | Nonsense 7; frameshift 5; splice 2; missense 1; intragenic deletion 1 |
| Mutation | c.1253_1254del | c.1630C>T | c.1685C>T | c.1995T>A | c.2214_2217del | c.2933del | c.3406dup | c.3408+1G>A | |
| Protein level | p.Lys418Argfs*54 | p.Arg544* | p.Pro562Leu | p.Tyr665* | p.Glu739Glyfs*20 | p.Pro978Hisfs*99 | p.Gln1136Profs*17 | p.? | |
| Location in gene | Exon 8 | Exon 10 | Exon 11 | Exon 12 | Exon 13 | Exon 15 | Exon 15 | Intron 15 | |
| Inheritance | De novo | De novo | De novo | Parents not tested | De novo | De novo | Parents not tested | De novo | |
| Level of intellectual disability/age at evaluation | Severe/4 years | Severe/3 years | Severe/22 years | Severe/12 years | Mild/8 years | Moderate/5 years | Severe/8.5 years | Severe/10 years | Mild n=2; moderate n=5; severe n=10/mean age at evaluation 8.7 years |
|---|---|---|---|---|---|---|---|---|---|
| Developmental stages | |||||||||
| Age of sitting/walking | 15–18 months/36 months | 12 months/walks only with aid | 12 months/38 months | NA/36 months | 8 months/18 months | 10 months/18months | 16 months/30 months | 25 months/4.5 years | Mean 12 months/ 27.7 months |
| Age of first words/first sentences | ∼29 months transient ‘mama’, ‘papa’/no sentences | 3 years ’papa’ only/no sentences | No words/no sentences | No words/no sentences | 12 months/6 years | 3 years/no sentences | 17 months/no sentences | No words/no sentences | Mean age first words 2.6 years |
| Current language ability | Absence of speech | Absence of speech | Absence of speech | Absence of speech | 120 words, 3- to 4-word sentences | 5 words | Absence of speech | Absence of speech | Absence of speech 7; speaks words 5; associates words or simple sentences 3 |
| Regressive episode during the development/age | Since age of 36 months loss of ‘mama’, ‘papa’ | No | 12 months—with febrile seizures | No | 14 months | No | Loss of words at age 18–30 months | Possible (loss of 2-syllable words) | n=7 |
| Autism spectrum disorder | Yes | Too young to be evaluated | No | No | Yes | No | Yes | Yes | Yes 8; no 8 |
|---|---|---|---|---|---|---|---|---|---|
| Clinical examination | |||||||||
| Age at examination | 5.2 years | 3 years | 22 years | 12 years | 8 years | 7 years | 8.5 years | 6.6 years | Mean 8.9 years |
| Height in cm (SD)/weight in kg (SD)/head circumference in cm (SD) | 149 (+1.5)/48.6 (+2)/52 (−1.5) | 105 (−0.5)/20 (+1.5)/49.3 (−1) | 93 (0)/13.8 (0)/48 (−2) | 146.5 (+1)/35 (+0.5)/55 (+1) | NA/21 (−1)/54 (+1) | 116 (+1)/21 (+1)/50 (0) | 124 cm (−1.5)/22 kg (−1.8)/50.8 cm (−1.7) | 116 cm (+0.4)/22.3 kg (+0.7)/51.3 cm (+0.4) | Normal OFC 15/15 |
| Neurological examination | Truncal hypotonia, broad-based gait, hypotonic-atactic movements | Truncal hypotonia, swallowing difficulties | Mild gait ataxia, flexion deformity of left hip, hyperlordotic lumbar spine | Hyperactive deep tendon reflexes, unsteady gait | Motor slowness and moderate akinesia, ataxic gait, truncal hypotonia, dystonic postures of hands and feet, plastic hypertonia | Truncal hypotonia, orthostatic truncal tremor, slight pyramidal tetraparesis, gait ataxia | Truncal hypotonia | Truncal hypotonia, orofacial hypotonia, wide-based gait | Clumsy/ataxic gait 10, truncal hypotonia 10, facial hypotonia 4, normal exam 2 |
*Patients are ordered by mutation from the 5′ end of the gene.
NA, not available; OFC, occipitofrontal circumference.