| |
Patient1
|
Patient2
|
Patient3
|
Patient4
|
Patient5
|
Patient6
|
Patient7
|
Patient8
|
Patient9
|
Patient10
|
Patient11
|
Patien12
|
Patient13
|
|---|
|
Age
|
3y0m
|
2y3m
|
6y8 m
|
4y2m
|
4y9m
|
4y6m
|
16y
|
4y8 m
|
7y4m
|
9y
|
2y10m
|
3y6m
|
2y0m
|
|
Sex
|
F
|
M
|
M
|
F
|
F
|
F
|
M
|
M
|
M
|
M
|
M
|
M
|
M
|
|
Elevated p-S6 protein (Relative density)
|
+ (3.4)
|
+ (3.0)
|
+ (3.8)
|
+ (3.6)
|
ND
|
+ (2.1)
|
+ (2.1)
|
+ (2.8)
|
+ (2.6)
|
- (0.8)
|
- (0.9)
|
- (1.1)
|
- (1.0)
|
|
Gene
|
AKT3
|
PIK3R2
|
PIK3R2
|
PTEN
|
PTEN
|
PTEN
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Mutation
|
c.686A > G p.(N229S)
|
c.1117G > A p.(G373R)
|
c.1117G > A p.(G373R)
|
c.640C > T p.(Q214*)
|
c.740 T > C p.(L247S)
|
c.1006C > G p.(Y336*)
|
Unknown
|
Unknown
|
Unknown
|
Unknown
|
Unknown
|
Unknown
|
Unknown
|
|
Inheritance
|
de novo
|
de novo
|
de novo
|
Mother negative
|
de novo
|
de novo
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Clinical features
|
|
Gestational age
|
36w5d
|
36w6d
|
40w1d
|
37w4d
|
38w6d
|
39w5d
|
36w6d
|
36w5d
|
41w0d
|
38w1d
|
39w
|
38w6d
|
38w3d
|
|
Birth weight g (SD)a
|
2942 (+1.4)
|
3450 (+2.7)
|
3532 (+1.2)
|
2536 (−0.3)
|
2854 (+0)
|
3200 (+0.7)
|
2915 (+1.0)
|
3490 (+3.0)
|
2464 (−2.3)
|
3885 (+3.3)
|
3830 (+2.6)
|
4120 (+3.5)
|
3866 (+3.0)
|
|
Birth length cm (SD)a
|
47.5 (+0.3)
|
49.2 (+1.0)
|
52.5 (+1.4)
|
47 (−0.4)
|
50 (+0.7)
|
51 (+1.0)
|
48 (+0.4)
|
48.8 (+0.9)
|
47 (−1.6)
|
50.6 (+1.3)
|
NA
|
NA
|
48.4 (+0)
|
|
Birth OFC cm (SD)a
|
39 (+4.9)
|
36 (+2.5)
|
34 (+0.4)
|
33 (+0.1)
|
33 (−0.1)
|
34 (+0.5)
|
35 (+1.8)
|
37 (+3.3)
|
30 (−2.0)
|
41 (+6.4)
|
36.5 (+3.0)
|
37 (+3.0)
|
39 (+4.6)
|
|
Birth OFC percentile a
|
>99
|
>99
|
67
|
53
|
44
|
70
|
96
|
>99
|
2
|
>99
|
>99
|
>99
|
>99
|
|
Last weight SDb
|
−1.9
|
0
|
−2.3
|
+0.4
|
−0.7
|
+0.8
|
−2.6
|
−0.2
|
−1.2
|
−0.2
|
+2.8
|
+2.2
|
+1.4
|
|
Last length SDb
|
−2.0
|
−0.2
|
−2.8
|
−0.4
|
−1.9
|
+0.2
|
−3.3
|
−1.3
|
−2.7
|
1.1
|
+0.7
|
−1.8
|
+0.2
|
|
Last OFC SDc
|
+6.3
|
+4.6
|
+3.0
|
+4.5
|
+4.3
|
+3.5
|
+4.9
|
+4.6
|
+2.0
|
+8.5
|
+5.4
|
+3.8
|
+4.5
|
|
Last OFC percentile c
|
>99
|
>99
|
>99
|
>99
|
>99
|
>99
|
>99
|
>99
|
98
|
>99
|
>99
|
>99
|
>99
|
|
Overgrowth /Asymmetry
|
-
|
+
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
+
|
-
|
+
|
-
|
|
Vascular malformations
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
+
|
-
|
-
|
+
|
|
Syndactyly
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
|
Polydactyly
|
-
|
-
|
-
|
-
|
-
|
-
|
+
|
-
|
-
|
+
|
-
|
+
|
-
|
|
Connective tissue dysplasia
|
-
|
+
|
-
|
-
|
-
|
-
|
-
|
-
|
+
|
-
|
-
|
-
|
-
|
|
Dysmorphic features
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
+
|
|
DQ (assessed method) age
|
DD
|
DQ 42 (Denver) 10 m
|
DD
|
DQ 76 (KIDS) 2y5m
|
DQ 85 (KIDS) 4y6m
|
DQ 59 (K-test) 4y1m
|
DQ 12 (KIDS) 6y6m
|
DQ 71 (K-test) 6y8 m
|
DQ 35 (KIDS) 5y9m
|
DD
|
DQ 72 (K-test) 3y0m
|
DQ 46 (K-test) 1y7m
|
NA
|
|
Meaningful words
|
-
|
-
|
-
|
1y6m
|
8 m
|
2y6m
|
+
|
2y
|
-
|
+
|
2y
|
-
|
-
|
|
Walking alone
|
-
|
-
|
-
|
2y4m
|
2y2m
|
1y6m
|
+
|
1y11m
|
1y11m
|
4y6m
|
1y6m
|
2y3m
|
1y3m
|
|
Hypotonia
|
+
|
+
|
+
|
-
|
+
|
-
|
+
|
+
|
+
|
-
|
-
|
+
|
+
|
|
Seizure
|
+
|
-
|
+
|
-
|
-
|
-
|
+
|
-
|
-
|
-
|
-
|
-
|
-
|
|
MRI findings
|
|
Ventriculomegaly
|
+
|
+
|
+
|
-
|
-
|
-
|
+
|
+
|
-
|
+
|
+
|
+
|
+
|
|
Polymicrogyria
|
+
|
+
|
+
|
-
|
-
|
-
|
+
|
-
|
-
|
+
|
-
|
+
|
-
|
|
Cerebellar tonsillar ectopia
|
-
|
-
|
-
|
-
|
-
|
-
|
-
|
+
|
-
|
+
|
-
|
+
|
-
|
|
White matter abnormalities
|
+
|
+
|
+
|
-
|
-
|
-
|
-
|
-
|
-
|
+
|
-
|
+
|
-
|
-
aSD and percentile were determined on the basis of the national data reported by the Ministry of Health, Welfare, and Labor in Japan in 2010
-
bSD was determined on the basis of the national data reported by the Ministry of Health, Welfare, and Labor in Japan in 2000
-
cSD and percentile were determined on the basis of CDC growth Charts for the United States in 2000
-
DD apparently developmentally delayed but not scored by a standardized method, Denver Denver Developmental Screening Test, DQ developmental quotient, F female, KIDS Kinder Infant Development Scale, K-test the revised version of Kyoto Scale of Psychological Development, M male, NA not available, OFC occipitofrontal circumference, p-S6 phosphorylated S6 protein, SD, standard deviation
- Accession number.: AKT3, NM_005465.4; PIK3R2, NM_005027.3; PTEN, NM_000314.5
