Table 3 Main clinical manifestations in 47 individuals with PTHS

Facial features

 Narrow forehead

4747

74%

127/150

85%

–

–

 Square forehead

47/47

100%

–

–

–

–

 Prominent forehead

42/47

89%

–

–

–

–

 Thin lateral eyebrows

31/47

66%

110/149

74%

–

–

 Wide nasal bridge/ridge/tip

44/47

94%

137/150

91%

44/45

98%

 Flared nasal alae

46/47

98%

119/150

79%

27/47

57%

 Full cheeks/prominent midface

47/47

100%

127/150

85%

36/48

77%

 Wide mouth/full lips/cupid bow upper lip

47/47

100%

142/150

95%

37/48

79%

 Thickened/overfolded helix

47/47

100%

96/141

68%

–

–

 Short philtrum

34/47

72%

–

–

 Deep-set eyes

42/47

89%

–

–

23/41

56%

 Up slanting palpebral fissures

43/47

91%

–

–

–

–

 Widely spaced teeth

25/33

76%

–

–

–

–

 Short neck

47/47

100%

–

–

–

–

Development

 Severe ID/GDD

42/44

95%

146/150

97%

48/48

100%

 Very limited or absent speech

29/32

91%

135/150

90%

32/48

68%

 Delayed gross motor development

47/47

100%

142/149

95%

44/48

94%

 Gait ataxia

27/29

93%

88/128

69%

26/48

55%

 Hypotonia

38/41

93%

104/142

73%

27/48

57%, > 90%[20]

Autonomic dysregulation

 Breathing anomalies

19/45

42%

81/145

56%

19/48

40%

  Intermittent hyperventilation

17/45

38%

72/145

50%

–

–

  Apnea

4/45

9%

61/145

42%

–

48%

 Gastrointestinal abnormalities

  Constipation

31/47

66%

115/142

81%

40/48

85%

  Food intolerances/allergy

17/21

81%

–

–

–

–

 Sleep disturbances

2/27

7%

–

–

7/39

18% [6]

Neurological/behavioral features

 Microcephaly

3/47

6%

28/144

19%

84/144

59%

 Brain MRI abnormalities

30/38

79%

–

–

–

60–70%[20]

  Ventricle enlargement

17/38

45%

–

–

–

–

  Wide extracranial space

13/38

34%

–

–

–

–

  Myelination dysplasia/delay

7/38

18%

36/96

38%

–

–

  Corpus callosum hypoplasia or agenesis

5/38

13%

–

–

–

–

  Frontal lobe dysplasia

2/38

5%

 Electroencephalogram abnormalities

5/33

15%

–

–

–

–

 Seizures

5/46

11%

55/1

37%

17/47

36%

 Smiling appearance

31/34

91%

31/140

22%

82/94

97%

 Anxiety/agitation

15/31

48%

–

–

32/67

48%

 Autism spectrum disorder

10/15

67%

61%[18]

 Regression

3/47

6%

6/150

4%

–

–

Visual anomalies

35/41

85%

–

–

25/48

53%

 Myopia

22/34

65%

78/144

54%

110/207

54%

 Strabismus

25/35

71%

70/144

49%

114/234

49%

 Astigmatism

19/34

56%

45/144

31%

–

–

Hand features

 Slender fingers

47/47

100%

63/130

48%

–

–

 Single transverse palmar crease

22/35

64%

60/120

50%

65/109

60%

 Stereotypic hand movements

39/39

100%

87/146

60%

83/107

78%

Genitourinary features

 Small penis/ Cryptorchidism^a

9/14

64%

–

–

–

33%