Table 1.
Genetic and clinical features of all presently and previously reported patients with GTPBP2-associated disorder
| Patients reported by present study | Family published by Jaberi et al. (ref. 5 ) | |||||
|---|---|---|---|---|---|---|
| Individual patients | Index family 1 | Index family 2 | Index family 3 | DS100-03 | DS100-04 | DS100-05 |
| Homozygous DNA variant in GTPBP2 | c.1219[C>T]; [C>T] | c.1408[C>T]; [C>T] | c.430[C>T]; [C>T] | c.1237-1[G>T]; [G>T] | ||
| Predicted alteration at protein level | p.(Gln407*) | p.(Arg470*) | p.(Arg144*) | p.(Val413TrpfsTer3) | ||
| General | ||||||
| Consanguinity | Yes | Yes | Yes | Yes | ||
| Family history | Negative | Positive | Negative | Positive | ||
| Age at last examination | 6 yrs. | 10 yrs. | 2 yrs. | 34 yrs. | 30 yrs. | 29 yrs. |
| Gender | Female | Male | Male | Female | Male | Male |
| Biometry at birth | ||||||
| Weight | 2.7 kg (5th perc.) | 3 kg (10th perc) | NA | NA | ||
| Height | NA | NA | NA | NA | ||
| Occipitofrontal head circumference | 36.5 cm at 1 month of age (25–50 perc) | NA | NA | NA | ||
| Biometry at last examination | ||||||
| Weight | 16 kg (<3rd perc) | 9.2 kg* (<5th perc) | 12.65 kg (25th perc) | NA | ||
| Height | 103 cm (<3rd perc) | 76 cm* (10th perc) | 88 cm (50th perc) | NA | ||
| Occipitofrontal head circumference | 45 cm (<3rd perc) | 42 cm* (<3rd perc) | 43.5 cm (<3rd perc) | NA | ||
| Development | ||||||
| Failure to thrive | Yes | No | No | None described | ||
| Motor development | Severe delay (unable to sit) | Severe delay (on wheel chair), severe wasting of muscles | Severe delay (no head control, unable to roll over) | Moderate delay (sitting at 1 year, walking at 2 years) | ||
| Intelectual disability (expressivity) | Severe (no words, no social smile) | Severe | Severe (no words, not fixating/following moving objects) | Moderate | ||
| Regression | No | NA | NA | No | ||
| Neurologic examination | ||||||
| Dystonia | No | No | No | Yes | ||
| Ataxia | No | No | No | Yes (wide-based gait) | ||
| Llimb spasticity | Yes | NA | No | No | ||
| Reflexes | Brisk | NA | Brisk | Reduced deep tendon reflexes | ||
| Tone | Increased in all limbs, joint stiffness, truncal hypotonia | Severe hypotonia | Increased in all limbs | No | Hypotonia | Hypotonia |
| Seizures | Yes | Yes | Yes | No | ||
| Other | No | No | Choreoathetosis | Tremor, abnormal hand posturing | ||
| Skeletal deformities | ||||||
| Spine | Mild thoracolumbar scoliosis | Dorsolumbar kyphoscoliosis | Scoliosis | No | Scoliosis | Scoliosis |
| Others | Stiffness of interphalangeal joints and knees, equinovarus deformities | Flexion deformity of fingers (clenched hands), bilateral talipes | Mild joint hypermobility | None reported | None reported | Pectus carinatum |
| Hearing impairment | No (normal auditory brainstem response audiometry) | No | No | None reported | ||
| Visual impairment | Yes (bilateral optic atrophy left>right, strabismus, nystagmus) | Yes (blindness) | Yes | Yes (retinal anomalies) | Yes (retinal anomalies) | Yes (early onset cataracts) |
| Dysmorphic/other features | Facial (depressed broad nasal bridge, bi-temporal narrowing, prominent ears), midline hair defect | Ectodermal dysplasia (sparse scalp hair, scanty eyebrows and eyelashes, abnormal dentition) | Facial (large low-set ears, small nose, triangular mouth), sparse scalp hair, sparse eyebrows, hypodentition | Sparse, thin and brittle hair | ||
| Brain MRI | ||||||
| Corpus callosum abnormalities | Partial hypogenesis (rostrum absent) | Agenesis | Partial hypogenesis (rostrum absent) | None described | ||
| Brain atrophy | Yes | Yes | Yes | None described | ||
| Cerebellar hypoplasia | Yes (inferior vermian hypoplasia) | None reported | Yes (cerebellar hypoplasia) | Yes (cerebellar vermian atrophy) | ||
| Dandy-Walker malformation | Yes | None reported | No | No | ||
| Others | Mild hydrocephalus, hypoplastic pituitary gland | Abnormally large subarachnoid spaces, subdural hemorrhage on right side of frontoparietal area | Hypointensities in globus pallidus and substantia nigra | |||
NA not available
* Biometry taken at age of 16 months