Table 1.
GA: Gestational age; HELLP syndrome: hemolysis, elevated liver enzymes, low platelet count, related with pregnancy; SD: standard deviation; OFC: occipito-frontal circumference; WIPPSI: Wechsler Preschool and Primary Scale of Intelligence; ADHD: attention deficit and hyperactivity disorder; MPD: Methyphenidate; MVRD: Midsaggital vermis relative diameter. * Subscores: Language 77, socialization 80, coordination 75, postural 34.
| Patient/Gender | 1 Female | 2 Male | 3 Female |
|---|---|---|---|
| Age | 8 years | 20 years | 7 years |
| Molecular findings/ inheritance |
c.4182C>A p.Phe1394Leu/De novo |
c.4991G>A p.Arg1664Gln/De novo |
c.5006G>A p.Arg1669Gln/De novo |
| Pregnancy & delivery/GA | Twin pregnancy/HELLP syndrome/C-section/ 35 weeks | Normal/eutocic/41 weeks | Normal pregnancy/forceps/40 + 6 weeks |
| Somatometry at birth (SD) | Weight 2150 g (+1.0SD) Height 43.5cm (+0.7 SD) OFC 32 cm (+0.5 SD) |
Weight 3520 g (+0,1 SD) Height 51 cm (+0.1 SD) OFC 36 cm (+0.4 SD) |
Weight 3400 g (+0.3 SD) Height 51 cm (+0.6 SD) OFC 35 cm (+0.1 SD) |
| Somatometry at last evaluation (SD) | 19.5 kg (−1.5 SD) 1.16 m (−0.5 SD) OFC 52.5 cm (+0.5 SD) |
77.2 kg (+0.2 SD) 176 m (−0.2 SD) OFC 59 cm (+1.5 SD) |
22.6 kg (−0.89 9 SD) 1.23 m (−0.69 7 SD) OFC 53.5 cm (+1.2 SD) |
| Initial neurological symptoms | Hypotonia Severe developmental delay |
Hypotonia Developmental delay |
Hypotonia Development delay |
| Cerebellar syndrome | Truncal ataxia and stereotypes Strabismus, terminal nystagmus | Mild ataxia/Dysarthria Oculomotor apraxia Nystagmus |
Mild ataxia |
| Neurodevelopment | Sitting position: 27 months Walk only with stroller: 5 years No speech (guttural sounds) Special schooling |
Sitting position: 8 months Independent walking: 30 months Language delay Occupational school |
Sitting position: 9 months Independent walking: 30 months Language Delay Ordinary school with support |
| Other neurological symptoms | Intellectual disability Autistic traits Attention deficit (treated with guanfacine) |
Mild intellectual disability Uncontrolled lateral head movements without consciousness abnormalities. | Mild intellectual disability Brunet−Lézine (30 months) 67 * WIPPSI IV (5.5 years): verbal IQ 70, performance IQ 68. ADHD (MPD) |
| Cranial magnetic resonance | 6 months: ventricular enlargement and increased extra−axial spaces. Normal posterior fossa structures. 16 months: cerebellar atrophy: increased interfolia spaces mainly in vermis. MVRD = 0.66 (mean for controls 0.77). 4 years 10 months: progression of generalized cerebellar atrophy. MVRD = 0.51 (mean for controls 0.80) |
6 years 10 months: cerebellar atrophy, with a MVRD = 0.76 (mean for controls 0. 82). 13 years 2 months: progressive generalized cerebellar atrophy. MVRD = 0.64 (mean for controls 0.87) |
15 months: no signs of cerebellar atrophy. 24 months: cerebellar atrophy: increase of interfolia spaces in the superior vermis |
| ICARS assessment | No collaboration, no comprehension | 17 years: 14/100 19 years: 12/100 |
4 years: 28/100 6 years: 19/100 |
| Acetazolamide therapy(at least during 8 months) | 12 mg/kg/day in two doses Improvement in muscle tone and communication intention. No objective positive response in the long term. |
250 mg /12 h Improvement in motor symptoms. Abolished stereotyped episodes. Withdrawn due to lithiasis |
12 mg/kg/day in two doses. No objective positive response |