Table 2.
A comparison of clinical findings of affected individuals reported with pathogenic variants in the KPTN gene
| Origin | Amish, Ohio | Amish, Ohio | Estonia |
Mixed, Kansas* | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genotype | Homozygous p.S259* | p.S259* /p.M241Q246Dup | Homozygous p.S223Qfs*50 | c.394 + 1G > A /p.M241Q 246Dup | n = 12 | |||||||||
| Patients | 1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | # | % |
| Gender | M | M | M | M | M | F | F | M | F | M | F | M | ||
| Age at evaluation (years) | 28.2 | 29 | 30 | 16.5 | 13.2 | 22.7 | 24.9 | 1.4 | 7.8 | 32 | 24 | 4 | ||
| Age at death (years) | n.a | 29 (head injury) | 30 (pneumonia) | n.a | n.a | n.a | n.a | n.a | n.a | n.a | n.a | 9 | ||
| Growth parameters | ||||||||||||||
| Birth weight, kg (SD) | 2.95 (0.7) | 2.92 (0) | 3.46 (+1.3) | 1.59 (−0.2) | 3.35 (−0.4) | 2.89 (+1.2) | 3.16 (−0.5) | 3.2 (+2.0) | 2.75 (+1.1) | ? | ? | 3.13 | ||
| Birth OFC, cm (SD) or birth macrocephaly reported | ? | 40.6 (+2.9) | 35.6 (+1.75) | ? | 51 (+3.9) | ? | ? | macrocephaly | macrocephaly | 34 (N) | 37 (N) | macrocephaly | 5 | 41.7 |
| Height, cm (SD) at evaluation | 166.7 (−1.6) | ? | 165.1 (−1.8) | 169 (−0.7) | 161.6 (+0.6) | 156.2 (−1.3) | 160.0 (−0.6) | ? | 123.5 (−0.4) | N | N | 100.0 (25th) | ||
| Weight, kg (SD) | 121.2 (+3.4) | ? | 66.2 (−0.2) | 63.1 (+0.1) | 51.5 (+0.8) | 107.9 (+3.6) | 82 (+2.2) | ? | ? | N | N | 16.8 (50th) | ||
| OFC, cm (SD) | 62 (+3.0) | ? | 63.5 (+3.6) | 62.5 (+3.4) | 61 (+3.3) | 63 (+5.4) | 60 (+3.2) | 52.5 (+3.2) | 55.5 (+2.1) | 63 (+4.5) | 60 (+4.0) | 57.0 (98th) | 11 | 91.7 |
| Parental OFC, cm (SD) | ? | Mother 55.5 (+0.1); Father 60 (+1.7) | ? | Mother 55.5 (+0.1); Father 60 (+1.7) | ? | Mother 58.5 (2.3) | ? | Mother 57 (+1.2); Father 59.5 (+1.5) | Mother 57 (+1.2); Father 59.5 (+1.5) | ? | ? | N | ||
| Development | ||||||||||||||
| Walked (years) | 1 | 1 | 1.33 | 1.9 | 4 | 3.8 | 2.4 | >2.2 | 2.2 | n.a | n.a | 2.5 | ||
| Expressive and receptive | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | 12 | 100.0 |
| Language deficit | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | nonverbal | 12 | 100.0 |
| Intellectual disability | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | 12 | 100.0 |
| Hearing | N | N | N | N | N | N | N | N | N | N | N | N | 0 | 0.0 |
| Neurology | ||||||||||||||
| Childhood hypotonia | –– | –– | –– | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ? | ? | ▪ | 7 | 58.3 |
| Seizures (onset) | AS/GTCS (3 mo) | AS/GTCS (7 yr) | GTCS (7 yr) | GTCS (10 mo) | GTC (3 mo) | 5 | 41.7 | |||||||
| Neuroimaging | N | ? | Ventriculomegaly | ? | ? | ? | ? | Widening of metopic suture | N | N | N | Abnormal** | 3 | 25.0 |
| Behavioral characteristics | ||||||||||||||
| Repetitive speech | ▪ | –– | –– | –– | ▪ | ▪ | ▪ | –– | –– | ▪ | –– | ▪ | 6 | 50.0 |
| Stereotypies | –– | –– | ▪ | ▪ | ▪ | ▪ | ▪ | –– | –– | ▪ | –– | ▪ | 7 | 58.3 |
| Hyperactivity | –– | –– | –– | ▪ | –– | –– | –– | –– | –– | ▪ | –– | ▪ | 3 | 25.0 |
| Autistic features | ? | ? | ? | ? | ? | ? | ? | ? | ? | ▪ | ▪ | ▪ | 3 | 25.0 |
| Anxiety | ▪ | –– | –– | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | 10 | 83.3 |
| Phobia | –– | –– | –– | –– | –– | –– | –– | ▪ | –– | ? | ? | –– | 1 | 8.3 |
| Physical anomalies | ||||||||||||||
| Frontal bossing | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | ▪ | 12 | 100.0 |
| High palate | ? | ? | ? | ? | ? | ? | ? | ? | ? | ▪ | ▪ | –– | 2 | 16.7 |
| Hypertelorism | –– | –– | –– | ▪ | –– | –– | –– | ▪ | –– | –– | –– | –– | 2 | 16.7 |
| Plagiocephaly | –– | –– | –– | ▪ | ▪ | –– | ▪ | ▪ | –– | –– | –– | –– | 4 | 33.3 |
| Prominent chin | ▪ | ▪ | ▪ | ▪ | –– | –– | –– | –– | ▪ | ▪ | ▪ | ▪ | 7 | 58.3 |
| Hepatosplenomegaly | –– | –– | –– | –– | –– | –– | ▪ | –– | –– | –– | –– | ▪ | 2 | 16.7 |
| Splenomegaly | –– | –– | –– | –– | –– | –– | –– | ▪ | –– | –– | –– | –– | 1 | 8.3 |
| Liver cirrhosis | –– | –– | –– | –– | –– | –– | ▪ | –– | –– | –– | –– | –– | 1 | 8.3 |
| Anemia | –– | –– | –– | –– | –– | –– | –– | ▪ | –– | –– | –– | –– | 1 | 8.3 |
| Recurrent Infections | –– | –– | ▪ | –– | –– | –– | ▪ | ▪ | –– | ? | ? | ▪ | 4 | 33.3 |
| 5th finger clinodactily | ▪ | ▪ | ▪ | –– | –– | –– | –– | –– | –– | –– | –– | –– | 3 | 25.0 |
| Fetal finger pad | –– | –– | –– | –– | –– | –– | –– | –– | ▪ | –– | –– | –– | 1 | 8.3 |
| Reference | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Baple et al. 2014 | Pajusalu et al. 2015 | Pajusalu et al. 2015 | n.a. | ||
(F) Female, (M) male, (OFC) occipitofrontal circumference, (SD) standard deviation score, (N/P) not performed, (▪) indicates presence of the clinical features in an affected individual, (–) indicates absence of the clinical features in an affected individual, (?) indicates the presence or absence of clinical features in an affected individual is unknown, (AS) absence of seizures, (GTC) generalized tonic-clonic seizures, (N) normal, ( n.a.) not applicable.