Table 1. .
Clinical Findings for Patients with TCF4 Mutations[Note]
| Finding for Patient |
||||||
| Characteristic | 1a | 2a | 3 | 4 | 5 | 6 |
| Sex | M | M | M | F | M | F |
| Age (years) | 14 | 11 | 8 | 12 | 29 | 29 |
| Birth: | ||||||
| Weight, in grams | 2,800 (>P3) | 2,620 (>P10) | 2,520 (>P25) | 2,450 (P10) | 3,660 (P50) | 2,500 (P3) |
| Length, in cm | 48 (10th) | 47 (P10) | 49 (>P50) | 46 (P3) | 53? cm (<P75) | NA |
| OFC, in cm | 33 (3rd) | 33 (25th) | 32.5 (25th) | 31.5 (10th) | NA | NA |
| Postnatal growth: | NA | NA | Weight P75 | Weight P10 | Weight <P3 | Weight <P3 |
| Height | −3 SD | −3 SD | P10–P25 | P25 | <P3 | <P3 |
| OFC | −3 SD | −5 SD | P25 | P25 | <P3 | <P3 |
| Walking | Steps with aid | Steps with aid | Steps with aid | At age 5 years; ataxic | At age 14 years; ataxic | At age 7 years; wide base |
| Speech | No | No | Single words | No | No | No |
| Seizures | At age 9 years | At age 8 years | No | No | No | No |
| Hypotonia | Yes | Severe | Severe | Severe | Yes | Yes |
| H-A | Daytime | Daytime | No | Daytime | Yes | Yes |
| Age at onset (years) | 5 | 6 | … | 8 | 2 | 5 |
| MRI anomalies | HCC, small hippocampus, and bulging caudate nuclei | HCC, small hippocampus, and bulging caudate nuclei | Dilated cerebral ventricles | HCC and bulging caudate nuclei | NA | CT only; no structural abnormality |
| SDFC (finger[s]) | No | No | Yes (3 and 4, BL) | Yes (2, 3, and 4, BL) | Yes (3 and 4, BL) | Yes (4) |
| SPC | Yes | No | Yes | Yes | Yes | NA |
| Happy disposition | Yes | Yes | Yes | Yes | Unmotivated laughter episodes | Yes |
| Intestinal anomalies | Constipation | HSCR | No | No | Severe constipation | No |
| Other anomalies | Broad finger tips and wide and flat palate | Broad finger tips and wide and flat palate | Strabismus, scoliosis, sacral dimple, fetal finger pads, overriding 5th toe, and short metatarsal V | Supernumerary nipple, scoliosis, and long and slender fingers and toes | Strabismus, very anxious, autoaggressive behavior, short hands and feet, and hyperconvex nails | Lymphoma, fetal finger pads, slender feet with short IV/V metatarsals, dislocated hips, and frontal cowlick |
| Test result: | ||||||
| AS methylation | NA | NA | Normal | Normal | Normal | NA |
| UBE3A | NA | NA | Normal | Normal | NA | NA |
| TCF4 | c.1726/1738C→T p.R576/580W de novo | 1.2-Mb deletion de novo | c.692-694insT p.G232fsX256 de novo | c.965-969delATGCT p.D322fsX336 de novo | c.1153C→T p.R385X | IVS9-1G→C |
Note.— All patients have distinctive PHS facial features and severe mental retardation. Results of karyotype tests and MECP2 tests were normal for all patients. AS methylation=methylation-sensitive PCR at the SNRPN locus concerning Angelman syndrome; BL=bilateral; H-A=episodes of hyperventilation-apnea; HCC=hypoplasia of corpus callosum; NA=not available; SDFC=supernumerary digital flexion crease; SPC=single palmar crease(s); P=percentile; OFC=occipitofrontal circumference.
a
Patients 1 and 2 were published as cases 1 and 2, respectively, by Peippo et al.3