Table 1.
Cerebral MRI scan and neurological features in 27 pediatric PHTS subjects.
| Pat.No | Sex | Mutation/Deletion in PTEN Gene (Localisation) | Age at DIAGNOSIS (Years) | Age at cMRI (Years) | Results of cMRI Scan | IQ > 85 | Delay in Motor Develop-ment | Muscle Hypotonia | Confirmed Autism | More Detailed Description of Neurological Features and Academic Performance | Age at Start of Walking Independently (Months) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| 1 | male | c.389G > A; Arg130 Gln (exon 5) | 3.8 | n.d. | n.d. | + | + | - | - | moderate delay in motor development, normal intelligence, secondary school −>university | 22 |
| 2 | male | c.389G > A; Arg130 Gln (exon 5) | 4 | 0.25 2.5 |
enlarged perivascular spaces | - | + | + | + | muscle hypotonia, autism, developmental delay in motor and language development, no expressive speech | 26 |
| 3 | male | c.540C > A; p.Y180X (exon 6) | 5.3 | 6 | enlarged perivascular spaces | + | + | - | - | delay of fine motor skills, normal intelligence, secondary school | 18 |
| 4 | male | c.737C > T.p.Pro246Leu (exon 7) | 1.3 | normal MRI scan (reported) | + | - | - | - | None, normal intelligence, secondary school | 17 | |
| 5 | male | c.209 + 5G > A (Intron 3) | 2 | 1.75 | white matter abnormalities, (periventricular posterior white matter), enlarged perivascular spaces | + | + | - | - | delay of gross and fine motor skills, normal intelligence, impulsivity, secondary school | 18 |
| 6 | male | c.445C > T; Gln149X (exon 5) | 3 | 2.0 | white matter abnormalities (posterior horn up to parietal white matter; smaller frontal and periventricular lesions), enlarged perivascular spaces | + | - | - | - | None, normal intelligence, elementary school | 18 |
| 7 | male | c.509G > A; pSer170Asn (exon 6) | 4 | n.d. | n.d. | + | + | - | - | moderat delay in fine motor skills, normal intelligence, elementary school | 14.5 |
| 8 | male | heterozygous deletion (exon 1–2) |
8 | 4.5 4.75 5.3 |
Ventriculo-peritoneal shunt, enlarged perivascular spaces | - | + | - | (-) | social behaviour problems, impulsivity, developmental delay, pseudotumor cerebri, Difficulties in regular school | ? |
| 9 | male | partial deletion (exon 6) | 1.5 | 1 2.5 4.5 |
Periventricular, occipital, parietal and and smaller frontal white matter abnormalities; enlarged perivascular spaces | + | + | + | - | muscle hypotonia, moderate delay in motor development, normal intelligence, secondary school diagnosis of PHTS because of MC and EPVS |
20 |
| 10 | male | c.697C > T;pArg233*(exon 7) | 11 | n.d. | n.d. | + | - | - | - | None, normal intelligence, secondary school | 18 |
| 11 | male | c.959T > G (p.Leu320*) | 7.5 | 0.3 7.8 8.3 9.3 |
Cavernoma right side cerebellum, enlarged perivascular spaces; slight parieto-occipital white matter abnormalities | + IQ 91 |
- | + | - | muscle hypotonia, difficulties in logical reasoning, impulsivity normal intelligence: HAWIK IV with 8 years: IQ 91 Special needs school | 14 |
| 12 | male | c.987dup T (p.Lys330*) (exon 8) | 6.5 | n.d. | n.d. | + IQ 84 |
+ | + | - | muscle hypotonia WPPSI-III, 2009–HAWIVA-III with 6 years: IQ 84, elementary school | 24 |
| 13 | male | c.(492 + 1_493–1)_(1026 + 1_1027–1)del | 0.9 | 0.6 | enlarged perivascular spaces | + | + | + | - | muscle hypotonia, delay in fine motor skills, normal intelligence, kindergarten | 19 |
| 14 | male | heterozygous deletion PTEN and BMPR1A Gene | 0.7 | 0.75 2 |
arachnoid cysts left and right of the pineal region, enlarged perivascular spaces, parietal and temporal white matter abnormalities (left sided pronounced), parietal Pacchioni granulation | + | - | + | - | muscle hypotonia | 18 |
| 15 | male | c.800_801delAG (exon 7) | 10 | 4.5 | enlarged perivascular spaces, slight parietal white matter abnormalities | −/+ IQ with 4.5 years: 70; with 5.9 years: IQ 89 |
+ | - | - | developmental delay in speech, cognition and motor development, HAWIWA III with 4.5 years: 70; HAWIVA III with 5.9 years: IQ 89, special needs school | 14 |
| 16 | male | c.464a > G; p.Tyr155Cys | 12 | 11.75 | enlarged perivascular spaces | + IQ 85 |
+ | - | - | problems in sense of balance, dyslexia, panic attacks, diagnosis of PHTS because of MC and EPVS | ? |
| 17 | male | p.Arg130Ter*;c.388C > T | 4.5 | n.d. | n.d. | + | + | - | - | delay in motor development, normal intelligence | 30 |
| 18 | male | c.266C > G (p.Pro89Arg) | 9 | 0.75 2.25 8 |
subependymal heterotopia at the top of the right lateral ventricle, enlarged perivascular spaces | + IQ 93 |
+ | + | + | delay in language and motor development. autism, ADHD, muscle hypotonia, obsessive-compulsive disorder, social behaviour problems, HAWIK: IQ 93, special needs school | 30 |
| 19 | female | c.741dupA; p.Pro248Thrfs*5 (exon 7) | 13.5 | n.d. | n.d. | + | - | - | - | None, secondary school −> university | 13 |
| 20 | female | c.302T > C; p.Ile101Thr (exon 5) | 5 | n.d. | n.d. | + IQ 89 |
+ | + | - | global developmental delay, muscle hypotonia, IQ testing: 89 | 24 |
| 21 | female | c.762dupA; p.Val255Serfs*43 (exon 7) | 5.5 | 6.2 | enlarged perivascular spaces | + IQ 96 |
+ | ++ | - | severe muscle hypotonia, difficulties in logical reasoning, HAWIK-IV/WISC-IV: IQ 96, special needs school | 24 |
| 22 | female | c.49C > T;p.Gln17* (exon1) | 6.8 | 8.5 | normal MRI scan, but enlarged perivascular spaces (reported) | + IQ 95 |
+ | + | - | ADHS, orofacial hypotonia, delay in motor development, normal intelligence, IQ with 6 years:95 Problems in elementary school |
18 |
| 23 | female | c.1008C > G;p.Tyr336* (exon 8) | 5.8 | 2.75 3 10.75 |
extremely large perivascular spaces, arachnoidal cysts | - | + | - | - | problems in sense of balance, ataxia, global developmental delay, special needs school | 19 |
| 24 | female | c.492delG; p.Gly165Glufs*2 (exon 5) | 2.8 | 1.25 | normal MRI scan enlarged perivascular spaces | + | - | - | - | None, normal intelligence, secondary school | 17 |
| 25 | female | c.1133_1136del.pArg378ilefs*37 (exon 9) | 3.5 | 1 | Chiari malformation type I, enlarged perivascular spaces | ? | + | - | - | delay in cross motor skills, language developmental delay, kindergarten | 29 |
| 26 | female | c.389G > A; p.(Arg130 Gln) (exon 5) | 2.3 | 0.8 | Supraventricular white matter abnormalities, left-sided; enlarged perivascular spaces | ? | + | + | - | muscle hypotonia, delay in language and motor development, kindergarten | 28 |
| 27 | female | c.406T > C(p.Cys136Arg) | 3 | n.d. | n.d. | ? | + | + | - | autism, muscle hypotonia, delay in language development, kindergarten | 20 |