Figure 1: Our patient was a 9 year old male with epilepsy, static encephalopathy, autism spectrum disorder, and (A) macrocephaly of unknown etiology who died of status epilepticus. (B) Several facial dysmorphisms were found, including frontal bossing, sunken eye sockets, down slanting palpebral fissures, small ears, thin upper lip, and small nose. (C) At four years old, he was with normal height and weight, but his head circumference measured 57 cm (>98th percentile)

Patients
1
2
3
4
5
6
7
8
9
10
11
12
#
%
Origin

Amish, Ohio

Amish, Ohio

Estonia

Mixed, Kansas*
n=12
Genotype

Homozygous p.S259*

p.S259* /p.M241Q246Dup

Homozygous p.S223Qfs*50

c.394+1G>A /p.M241Q

246Dup
Gender

M

M

M

M

M

F

F

M

F

M

F

M

Age at Evaluation (years)

28.2

29

30

16.5

13.2

22.7

24.9

1.4

7.8

32

24

4

Age at death (years)

n.a

29
(head injury)

30 (pneumonia)

n.a

n.a

n.a

n.a

n.a

n.a

n.a

n.a

9

Growth parameters

 

Birth weight kg (SD)

2.95 (0.7)

2.92 (0)

3.46 (+1.3)

1.59 (-0.2)

3.35 (-0.4)

2.89 (+1.2)

3.16 (-0.5)

3.2 (+2.0)

2.75 (+1.1)

?

?

3.13

 

 

Birth OFC cm (SD)  or Birth macrocephaly reported

?

40.6 (+2.9)

35.6 (+1.75)

?

51 (+3.9)

?

?

macrocephaly

macrocephaly

34 (N)

37 (N)

macrocephaly

5

41.7

Height  cm (SD) at evaluation

166.7 (-1.6)

?

165.1 (-1.8)

169 (-0.7)

161.6 (+0.6)

156.2 (-1.3)

160.0 (-0.6)

?

123.5 (-0.4)

N

N

100.0 (25th)

 

 

Weight kg (SD)

121.2 (+3.4)

?

66.2 (-0.2)

63.1 (+0.1)

51.5 (+0.8)

107.9 (+3.6)

82 (+2.2)

?

?

N

N

16.8 (50th)

 

 

OFC cm (SD)

62 (+3.0)

?

63.5 (+3.6)

62.5 (+3.4)

61 (+3.3)

63 (+5.4)

60 (+3.2)

52.5 (+3.2)

55.5 (+2.1)

63 (+4.5)

60 (+4.0)

57.0 (98th)

11

91.7

Parental OFC cm (SD)

?

Mother 55.5 (+0.1); Father 60 (+1.7)

?

Mother 55.5 (+0.1); Father 60 (+1.7)

?

Mother 58.5 (2.3)

?

Mother 57 (+1.2); Father 59.5 (+1.5)

Mother 57 (+1.2); Father 59.5 (+1.5)

?

?

N

 

 

Development

Walked (years)

1

1

1.33

1.9

4

3.8

2.4

>2.2

2.2

n.a

n.a

2.5

Expressive & Receptive

12

100.0

Language deficit

nonverbal

12

100.0

Intellectual disability

12

100.0

Hearing

N

N

N

N

N

N

N

N

N

N

N

N

0

0.0

Neurology

Childhood hypotonia

?

?

7

58.3

Seizures (onset)

AS/GTCS (3 mo)

AS/GTCS (7 yrs)

GTCS (7 yrs)

 

 

 

 

 

 

GTCS (10 mo)

 

GTC (3 mo)

5

41.7

Neuroimaging

N

?

Ventriculo-megaly

?

?

?

?

Widening of metopic suture

N

N

N

Abnormal**

3

25.0

Behavioral characteristics

Repetitive speech

6

50.0

Stereotypies

7

58.3

Hyperactivity

3

25.0

Autistic features

?

?

?

?

?

?

?

?

?

3

25.0

Anxiety

10

83.3

Phobia

?

?

1

8.3

Physical anomalies

Frontal bossing

12

100.0

High palate

?

?

?

?

?

?

?

?

?

2

16.7

Hypertelorism

2

16.7

Plagiocephaly

4

33.3

Prominent chin

7

58.3

Hepatosplenomegaly

2

16.7

Splenomegaly

1

8.3

Liver cirrhosis

1

8.3

Anemia

1

8.3

Recurrent Infections

?

?

4

33.3

5th finger clinodactily

3

25.0

Fetal finger pad

1

8.3

Reference:

4

4

4

4

4

4

4

4

4

5

5

n.a

   
Abbreviations: F, female; M, male; OFC, occipitofrontal circumference; SD, standard deviation score; N/P, not performed; (■), indicates presence of the clinical features in an affected individual; (−), indicates absence of the clinical features in an affected individual; (?), indicates the presence or absence of clinical features in an affected individual is unknown; AS, absence seizures; GTC, generalized tonic clonic seizures; N, normal; MO, months; YR, years; n.a, not applicable
Table 1: A comparison of Clinical Findings of Affected individuals reported with pathogenic variants in KPTN gene