Clinical and molecular findings of patients with CDK5RAP2 mutations
| Family | 1 | 1 | 2 | 3 | 3 | 4 | 5 |
| Subject | Patient 1 | Patient 2 | Patient 3 | Patient 4 | Patient 5 | Patient 6 | patient 7 |
| Gender | M | F | F | F | M | M | F |
| CDK5RAP2 variant | c.564_565dup (p.Lys189Argfs*15) | c.564_565dup (p.Lys189Argfs*15) | c.5495dup, (p.Leu1832Phefs*3) ; c.217-220del, (p.Glu73Thrfs*4) | c.1303dup (p.Thr435Asnfs*4) | c.1303dup (p.Thr435Asnfs*4) | c.558_559del, (p.Glu186Aspfs*32) ; c.4441C>T, (p.Arg1481*) | c.3928G>T, (p.Glu1310*) ; c.4546G>T, (p.Glu1516*) |
| Ethnic origin | Tunisia | Tunisia | Serbia | Morocco | Morocco | Italian/Romanian | Swiss/Austrian |
| Consanguinity | Yes | Yes | Yes | Yes | Yes | No | No |
| Mother HC (cm, SD) | 56 (+1) | 56 (+1) | 54.5 (0) | Not available | Not available | 53 cm | Not available |
| Father HC (cm, SD) | 60 (+3.5) | 60 (+3.5) | 57.5 (+1.5) | Not available | Not available | 58.5 cm | Not available |
| Pregnancy duration (weeks of amenorrhoea) | 38 | 40 | 39 | 39 | 38 | 41 | 39 |
| Prenatally diagnosed microcephaly (ultrasounds) | Third trimester | Second trimester | Non-reported microcephaly | Non-reported microcephaly | Third trimester | Second trimester | Third trimester |
| Fetal cranial MRI | Not performed | Not performed | Not performed | Not performed | Not performed | Not available | Not performed |
| Weight at birth (kg, SD) | 2.490 (−2) | 3.160 (−0.5) | 2.965 (−1) | 2.260 (−2.5) | 1.520 (−3.5) | 2.900 (−1.5) | 2.005 (−3) |
| Length at birth (cm, SD) | 45 (−3.5) | 45 (−3) | 47 (−2.5) | 45 (−3) | 41 (−5.5) | 46 (−3) | 44 (−3) |
| HC at birth (SD) | 31 (−2.2) | 30.5 (−2.5) | 30.5 (−2.5) | 29.5 (−3) | 26.5 (−5) | 30.5 (−2.5) | 28 (−4) |
| Age at last examination (years) | 10 | 4.5 | 4.5 | 11 | 10 | 8 | 14.5 |
| Weight at last examination (kg, SD) | 52.5 (+5.5) | 12.5 (−2) | 19.5 (+2) | 48.3 (+3) | 21.5 (−2) | 26 (+0.5) | 34.3 (−3) |
| Length at last examination (m, SD) | 1.34 (0) | 0.94 (−2) | 1.07 (+1) | 1.44 (+0.5) | 1.27 (−1.5) | 118 (−1.5) | 146.4 (−2) |
| HC at last examination (cm, SD) | 48.5 (−3.4) | 42 (−6.6) | 42.5 (−6.2) | 47.5 (−4) | 42 (−7.7) | 42.8 cm (−7.2) | 43.2 (−7.3) |
| Development | |||||||
| Age of walking (months) | 10.5 | 16 | 14 | 11 | 18 | 12 | 18 |
| Mastication (if delayed, age in months) | Delayed (24) | Delayed (24) | Normal | Normal | Delayed (24) | Delayed (30–36) | Normal |
| Age of first comprehensive words (months) | 18 | 18 | 30 | 24 | 54 | 18 | 21 |
| Age of first sentences (years) | 4.5 | 2 | 4.5 | 3 | Unvested, severe articulation disorders | 8 | 3.5 |
| Language articulation (normal, delayed) | Normal | Normal | Delayed | Normal | Delayed | Delayed (30 mo) | Delayed |
| Social interaction (normal/delayed) | Normal | Normal | Normal | Normal | Normal | Normal | Normal |
| Years in kinder garden | 3 | 0 | 1 | ||||
| Elementary school | First year in normal class, then home schooling | ||||||
| Seizures | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Neurological findings | |||||||
| Hypertonia within the first 2 years of life | 0 | 0 | 0 | 0 | 0 | Yes | Yes |
| Hypotonia within the first 2 years of life | 0 | 0 | 0 | 0 | 0 | No | Axial hypotonia |
| Pyramidal syndrome | 0 | 0 | 0 | 0 | 0 | No | 0 |
| Inferior limb spasticity | 0 | 0 | 0 | 0 | 0 | Yes | Yes |
| Ataxia | 0 | 0 | 0 | 0 | 0 | Incoordinate movements | Yes |
| Behaviour | |||||||
| Hyperactivity | Yes | Yes | Yes | Before 7–8 years | Before 7–8 years | Quiet behaviour, but hyperactivity episodes | No |
| Tic disorders | No | No | No | No | 0 | (but repetitive movements) | No |
| Agressiveness | No | No | No | No | 0 | Episodes of aggressiveness | No |
| Intellectual abilities | |||||||
| Total IQ | 62 | 67 | 40 | 56 | 52 | 46 | |
| Sensorineural anomalies | |||||||
| Congenital hearing loss (unilateral/bilateral) | No | No | No | No | No | 0 | No |
| Progressive hearing loss (uni/bilateral), age | Bilateral, 9 years | No | Unilateral, 7 years | No | Bilateral, 7 years | Bilateral, 10 years | No |
| Hearing (auditory threshold) | Right: severe deafness (70–80 dB) Left: moderate deafness (20–50 dB) | Normal oto-acoustic emissions within the first months of life | Right: severe deafness (70 dB) Left: normal | Right: normal (15–20 dB) Left: normal (15–25 dB) | Right: severe deafness (80–90 dB) Left: severe deafness (60–70 dB) | Right: severe deafness (60–80 dB) Left: moderate-to-severe deafness (40–60 dB/60–80 dB) | Right and left: normal |
| Hearing aid (unilateral/bilateral) | Unilateral | No | Unilateral | No | Bilateral | Bilateral | No |
| Retinal hypopigmentation (unilateral/bilateral) | Bilateral | Bilateral | Bilateral | Bilateral | Bilateral | ? | Yes |
| Retinal hyperpigmentation (unilateral/bilateral) | Bilateral | Bilateral | Bilateral | Bilateral | Bilateral | ? | No |
| ERG | Normal | Normal | Normal | Normal | Normal | Not done | Normal |
| Skin anomalies | |||||||
| Area of hypopigmentation | Yes | Yes | Yes | No | No | No | Yes |
| Area of hyperpigmentation | Yes | Yes | No | Yes | Yes | Yes (several cafè-au-lait spots on trunk, arms and legs) | Yes |
CC, corpus callosum; ERG, electroretinogram; HC, head circumference; IQ, intellectual quotient.