Table 1.
Clinical features of patients
| Patient | V:1 | V:5 | V:6 | V:7 |
|---|---|---|---|---|
| Age at time of assessment (years) | 15.06 | 7.28 | 3.12 | 1.60 |
| Sex | Male | Male | Male | Female |
| Head circumference (SDS/cm) | −3.23 (51.0) | −1.69 (51.0) | −2.03 (48.7) | −3.55 (44.0) |
| Height (SDS/cm) | −2.24 (149.5) | −2.97 (108) | −2.17 (88.3) | −1.93 (76.2) |
| Development: | ||||
| Gross motor | A few independent steps, gradual decline in motor function | Cruises furniture, gradual decline in motor function | Cruises furniture | Crawling |
| Speech | Dysarthric, nasal speech, short sentences | Dysarthric, nasal speech, 2– 3-word sentences | A few single words | Babbling |
| Intellectual disability | Mild | Mild | Mild | |
| Neurology: | ||||
| Upper limb | ||||
| Spasticity | ✓ | x | x | x |
| Lower limb | ||||
| Spasticity | ✓ | ✓ | ✓ | ✓ |
| Hyperreflexia | ✓ | ✓ | ✓ | ✓ |
| Ankle clonus | ✓ | ✓ | x | ✓ |
| Extensor plantar responses | ✓ | ✓ | ✓ | ✓ |
| Brain MRI | High intensity signal in the periventricular trigonal area with atrophy in surrounding white matter | Increased T2 intensity signal in periventricular and subcortical white matter and along optic radiation | Increased T2 signal intensity in the periventricular white matter | Increased T2 signal intensity in the periventricular region more pronounced around the atria of the lateral ventricles |
| Nerve Conduction Studies | Motor conduction study of median/ulnar and common peroneal nerves – normal CMAP parameters (amplitude, latency, F-responses and conduction velocity). | Normal (age 5 years) | Borderline prolongation of the median nerve motor latencies, otherwise normal (age 3 years) | Normal |
| Median/ulnar and sural nerve sensory study – normal | ||||
| Posterior tibial CMAP amplitude – severely reduced and dispersed, borderline decline in conduction velocity. (age 11 years) | ||||
| Ophthalmic phenotype | Reduced visual acuity | Photophobic | Age appropriate visual behaviour | Age appropriate visual behaviour |
| No refractive error | Reduced visual acuity | Normal refraction | Mild hyperopic astigmatism | |
| No further phenotyping | Mild hyperopic astigmatism | Normal anterior segment | Mild retinal vessel tortuosity | |
| Mild retinal vessel tortuosity | RPE pigmentary disturbance | Dull macular reflex | ||
| Generalized RPE level pigmentary disturbance | No further phenotyping | No further phenotyping | ||
| Dull macular reflex | ||||
| Normal anterior segment | ||||
| ffERG findings of cone-rod dysfunction. | ||||
| No further phenotyping | ||||
| Cleft palate/bifid uvula | Bifid uvula, cleft palate | x | High arched palate | Bifid uvula |
Height, weight and OFC Z-scores were calculated using a Microsoft Excel add-in to access growth references based on the LMS method (Pan and Cole, 2012) using a reference European population (Cole et al., 1998).
SDS = standard deviation scores; ✓ = presence of a feature in an affected subject; × indicates absence of a feature in an affected subject; CMAP = compound muscle action potential; RPE = retinal pigment epithelium; ffERG = full-field electroretinography.