Table 3 Clinical and neuroimaging features related to FOXG1 genotype groups in 76 patients with FOXG1 syndrome

From: FOXG1 syndrome: genotype–phenotype association in 83 patients with FOXG1 variants

FOXG1 genotype group

 

Group 1:

Group 2:

Group 3:

Group 4:

Group 5:

Association with FOXG1 variant

  

N-terminal

forkhead cs

forkhead

forkhead

C-terminal

2-group comparison:

5-group

  

fsh + non

missense

fsh + non

missense

fsh + non

group 1 vs. other

comparison

Sample percent, n

 

48.7%

37

15.8%

12

11.8%

9

11.8%

9

11.8%

9

P-multivar

P-univar

P-univar

Severity score

Median[IQ]

1.4 [1.3, 1.6]

0.9 [0.7, 1.1]

1.4 [1.3, 1.5]

1.3 [1.1, 1.3]

1.2 [0.7, 1.4]

–

0.0043

0.0161

Somatic growth: multivariate

0.3204

–

–

 Length at follow-up

 < −2 SD

53%

9/17

14%

1/7

80%

4/5

75%

3/4

43%

3/7

 

1.0000

0.1795

 BMI at follow-up

 < −2 SD

29%

5/17

57%

4/7

20%

1/5

75%

3/4

14%

1/7

 

0.7385

0.2115

 HC at follow-up

 < −2 SD

96%

23/24

50%

5/10

100%

5/5

100%

8/8

75%

6/8

 

0.1191

0.0074

 HC at birth

 < −2 SD

33%

6/18

13%

1/8

20%

1/5

50%

3/6

0%

0/8

 

0.3040

0.1803

Motor and speech development: multivariate

0.0007

–

–

 Sitting

Absent

50%

8/16

10%

1/10

80%

4/5

14%

1/7

38%

3/8

 

0.0003

0.00009

 

Assisted

38%

6/16

0%

0/10

20%

1/5

0%

0/7

0%

0/8

   

 Walking

Absent

91%

31/34

33%

4/12

100%

9/9

56%

5/9

56%

5/9

 

0.0071

0.0001

 

Assisted

3%

1/34

8%

1/12

0%

0/9

33%

3/9

22%

2/9

   

 No functional hand use

 

72%

23/32

8%

1/12

88%

7/8

43%

3/7

44%

4/9

 

0.0155

0.0004

 No verbal speech

 

86%

30/35

67%

8/12

100%

7/7

75%

6/8

56%

5/9

 

0.2454

0.1211

Behavior: multivariate

0.2632

–

–

 Social interaction

Absent

19%

6/31

0%

0/8

17%

1/6

0%

0/7

0%

0/8

 

0.1381

0.1328

 

Poor

19%

6/31

13%

1/8

0%

0/6

57%

4/7

50%

4/8

   

 Eye contact

Absent

12%

2/17

14%

1/7

0%

0/5

0%

0/7

14%

1/7

 

0.5229

0.5683

 

Poor

59%

10/17

14%

1/7

60%

3/5

57%

4/7

57%

4/7

   

 Abnormal sleep pattern

 

70%

16/23

57%

4/7

20%

1/5

100%

7/7

78%

7/9

 

1.0000

0.0480

Neurological features: multivariate

0.0098

–

–

 Epilepsy

 

81%

29/36

75%

9/12

67%

6/9

22%

2/9

56%

5/9

 

0.0289

0.0160

 Spasticity

 

76%

13/17

13%

1/8

50%

2/4

71%

5/7

57%

4/7

 

0.0637

0.0346

 Stereotypic movements

 

85%

23/27

75%

6/8

100%

5/5

100%

7/7

100%

9/9

 

0.4141

0.3991

 Dyskinesia

 

96%

23/24

73%

8/11

80%

4/5

100%

8/8

86%

6/7

 

0.2162

0.1313

 Feeding difficulties

 

100%

21/21

75%

6/8

100%

4/4

100%

5/5

50%

3/6

 

0.0497

0.0078

 Kypho-/scoliosis

 

39%

7/18

33%

2/6

80%

4/5

33%

2/6

29%

2/7

 

1.0000

0.4631

MRI features: multivariate

0.0128

–

–

 Corpus callosum anomalies

 

83%

20/24

33%

3/9

83

5/6

20%

1/5

57%

4/7

 

0.0176

0.0083

 Delayed myelination

 

78%

14/18

43%

3/7

100

3/3

0%

0/3

17%

1/6

 

0.0201

0.0034

 Cortical anomalies

 

70%

16/23

50%

3/6

75

3/4

83%

5/6

67%

4/6

 

1.0000

0.8519

Age at last follow-up (months)a

Median (IQ)

72 [43, 125]

89 [63, 138]

46 [28, 60]

96 [78, 192]

89 [60, 204]

–

0.8412

0.1811

 

Range

24–384

20–216

14–264

31–216

31–372

   
  1. BMI, body mass index; fsh, frameshift; HC, head circumference; IQ; interquartile range; non, nonsense; P-multivar, P value of joint test of several measures; P-univar, P value of test of single measure.
  2. Displayed are observed percentages of clinical, neurological, and behavioral anomalies and sample sizes within FOXG1 genotype groups for a total of n = 76 patients with FOXG1 syndrome. Significant P values for genotype–phenotype association are set bold, borderline significant P values are underlined. Multiple-testing adjusted significance levels were: α = 0.0287 (severity score of the displayed 20 clinical, neurological, and behavioral measures, Kruskal–Wallis rank-sum tests), α = 0.00909 (2-group comparisons: multivariate rank-sum tests on phenotypic categories (P-multivar) and closed testing principle on Fisher’s exact tests of contributing measures), α = 0.00188 (5-group comparisons: Fisher’s exact tests). 2-group and 5-group comparisons (P-multivar, P-univar) included all 20 displayed clinical, neurological, and behavioral measures and in addition: loss of motor skills, unexplained episodes of crying, paroxysmal laughter, strabismus, bruxism, hypersalivation, abnormal breathing pattern, gastric reflux, constipation (see Supplementary Table S3 online for a full version of this table). No association testing with FOXG1 genotypes was performed for diagnoses that were very rare (nystagmus, hypoplastic hippocampi, pachygyria), very frequent (hypotonia), or had very low numbers of observations in any FOXG1 genotype group (aspiration, autistic behavior).
  3. aAge at last follow-up did not significantly differ between FOXG1 genotype groups (Kruskal–Wallis rank-sum test). Full version is provided as Supplementary Table S3.
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