Table 1

Clinical and molecular findings of patients with CDK5RAP2 mutations

SubjectPatient 1Patient 2Patient 3Patient 4Patient 5Patient 6patient 7
CDK5RAP2 variantc.564_565dup (p.Lys189Argfs*15)c.564_565dup (p.Lys189Argfs*15)c.5495dup, (p.Leu1832Phefs*3) ;
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 originTunisiaTunisiaSerbiaMoroccoMoroccoItalian/RomanianSwiss/Austrian
Mother HC (cm, SD)56 (+1)56 (+1)54.5 (0)Not availableNot available53 cmNot available
Father HC (cm, SD)60 (+3.5)60 (+3.5)57.5 (+1.5)Not availableNot available58.5 cmNot available
Pregnancy duration (weeks of amenorrhoea)38403939384139
Prenatally diagnosed microcephaly (ultrasounds)Third trimesterSecond trimesterNon-reported microcephalyNon-reported microcephalyThird trimesterSecond trimesterThird trimester
Fetal cranial MRINot performedNot performedNot performedNot performedNot performedNot availableNot 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)104.54.51110814.5
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)
Age of walking (months)10.5161411181218
Mastication (if delayed, age in months)Delayed (24)Delayed (24)NormalNormalDelayed (24)Delayed (30–36)Normal
Age of first comprehensive words (months)18183024541821
Age of first sentences (years)4.524.53Unvested, severe articulation disorders83.5
Language articulation (normal, delayed)NormalNormalDelayedNormalDelayedDelayed (30 mo)Delayed
Social interaction (normal/delayed)NormalNormalNormalNormalNormalNormalNormal
Years in kinder garden301
Elementary schoolFirst year in normal class, then home schooling
Neurological findings
Hypertonia within the first 2 years of life00000YesYes
Hypotonia within the first 2 years of life00000NoAxial hypotonia
Pyramidal syndrome00000No0
Inferior limb spasticity00000YesYes
Ataxia00000Incoordinate movementsYes
HyperactivityYesYesYesBefore 7–8 yearsBefore 7–8 yearsQuiet behaviour, but hyperactivity episodesNo
Tic disordersNoNoNoNo0(but repetitive movements)No
AgressivenessNoNoNoNo0Episodes of aggressivenessNo
Intellectual abilities
Total IQ626740565246
Sensorineural anomalies
Congenital hearing loss (unilateral/bilateral)NoNoNoNoNo0No
Progressive hearing loss (uni/bilateral), ageBilateral, 9 yearsNoUnilateral, 7 yearsNoBilateral, 7 yearsBilateral, 10 yearsNo
Hearing (auditory threshold)Right: severe deafness (70–80 dB)
Left: moderate deafness (20–50 dB)
Normal oto-acoustic emissions within the first months of lifeRight: 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)UnilateralNoUnilateralNoBilateralBilateralNo
Retinal hypopigmentation (unilateral/bilateral)BilateralBilateralBilateralBilateralBilateral?Yes
Retinal hyperpigmentation (unilateral/bilateral)BilateralBilateralBilateralBilateralBilateral?No
ERGNormalNormalNormalNormalNormalNot doneNormal
Skin anomalies
Area of hypopigmentationYesYesYesNoNoNoYes
Area of hyperpigmentationYesYesNoYesYesYes (several cafè-au-lait spots on trunk, arms and legs)Yes
  • CC, corpus callosum; ERG, electroretinogram; HC, head circumference; IQ, intellectual quotient.