Table 2

The frequency thyroid function, plasma amino acids, urine organic acids, microarray, karyotype and MR imaging were positive subgroups of additional features

ParticipantsNo of participants in whom a cause was found (%)Investigations
No of participants receiving investigation/no of diagnostic tests (%)
TFTPlasma amino acidsUrine organic acidsKaryotypeMicroarrayFragile XMRI brain
All participants with EDI and additional features (n=557)152 (27.3%)378 (67.9%)
3/378 (0.8%)
338 (60.7%)
5/338 (1.5%)
265 (47.6%)
3/265 (1.1%)
86 (15.4%)
2/86 (2.3%)
363 (65.2)
42/363 (11.6%)
89 (16.0%)
0/89 (0%)
338 (60.7%)
81 (24.0%)
Additional features and a family history of EDI/LD or neurological disease like seizures (n=115)26 (22.6%)82 (71.3%)
1/82 (1.2%)
75 (65.2%)
1/75 (1.3%)
50 (43.5%)
0/50 (0%)
13 (11.3%)
0/13 (0%)
81 (70.4%)
10/81 (12.3%)
19 (16.5%)
0/19 (0%)
67 (58.3%)
10/67 (14.9%)
Consanguinity admitted by family (n=26)7 (26.9%)20 (76.9%)
0/20 (0%)
17 (65.4%)
0/17 (0%)
15 (57.7%)
0/15 (0%)
4 (15.4%)
0/4 (0%)
16 (61.5%)
2/16 (12.5%)
2 (7.7%)
0/2 (0%)
16 (61.5%)
5 (31.3%)
Dysmorphia (n=132)38 (28.8%)95 (72.0%)
0/95 (0%)
89 (67.4%)
2/89 (2.2%)
68 (51.5%)
1/68 (1.5%)
14 (10.6%)
0/14 (0%)
110 (83.3%)
13/110 (11.8%)
20 (15.2%)
0/20 (0%)
91 (68.9%)
19/91 (20.9%)
Macrocephaly (n=33)8 (24.2%)22 (66.7%)
0/22 (0%)
20 (60.6%)
0/20 (0%)
15 (45.5%)
0/15 (0%)
3 (9.1%)
0/3 (0%)
23 (69.7%)
4/23 (17.4%)
5 (15.2%)
0/5 (0%)
25 (75.8%)
4/25 (16.0%)
Microcephaly (n=162)46 (28.4%)110 (67.9%)
1/110 (0.9%)
106 (65.4%)
2/106 (1.9%)
85 (52.5%)
1/85 (1.2%)
27 (16.7%)
1/27 (3.7%)
112 (69.1%)
15/112 (13.4%)
27 (16.7%)
0 (0%)
100 (61.7%)
24 (24.0%)
Hypertonia/upper motor neuron findings (spasticity, dystonia, brisk reflexes) (n=82)40 (48.8%)56 (68.3%)
0/56 (0%)
57 (69.5%)
1/57 (1.8%)
51 (62.2%)
0/51 (0%)
10 (12.2%)
0/10 (0%)
60 (73.2%)
4/60 (6.7%)
3 (3.7%)
0/3 (0%)
79 (96.3%)
31 (39.2%)
Hypotonia (n=84)27 (32.1%)57 (67.9%)
1/57 (1.8%)
54 (64.3%)
1/54 (1.9%)
47 (56.0%)
0/47 (0%)
10 (11.9%)
0/10 (0%)
56 (66.7%)
5/56 (8.9%)
8 (9.5%)
0/8 (0%)
65 (77.4%)
18/65 (27.7%)
Gait abnormalities, tremor, cerebellar signs or other movement disorders (n=49)17 (34.7%)37 (75.5%)
0/37 (0%)
28 (57.1%)
0/28 (0%)
24 (49.0%)
0/24 (0%)
11 (22.4%)
0/11 (0%)
26 (53.1%)
3/26 (11.5%)
4 (8.2%)
0/4 (0%)
39 (79.6%)
11/39 (28.2%)
Epilepsy (n=29)17 (58.6%)17 (58.6%)
0/17 (0%)
22 (75.9%)
1/22 (4.5%)
16 (55.2%)
0/16 (0%)
4 (13.8%)
0/4 (0%)
17 (58.6%)
2/17 (11.8%)
1 (3.4%)
0/1 (0%)
27 (93.1%)
10/27 (37.0%)
Ophthalmological signs (n=96)43 (44.8%)64 (66.7%)
1/64 (1.6%)
59 (61.5%)
2/59 (3.4%)
46 (47.9%)
0/46 (0%)
15 (15.6%)
0/15 (0%)
64 (66.7%)
7/64 (10.9%)
9 (9.4%)
0/9 (0%)
78 (81.3%)
28/78 (35.9%)
Hearing difficulties (n=27)7 (25.9%)17 (63.0%)
0/17 (0%)
18 (66.7%)
0/18 (0%)
15 (55.6%)
0/15 (0%)
2 (7.4%)
0/2 (0%)
18 (66.7%)
2/18 (11.1%)
2 (7.4%)
0/2 (0%)
22 (81.5%)
4/22 (18.2%)
Cardiac disorder, including congenital cardiac lesions (n=24)8 (33.3%)14 (58.3%)
0/14 (0%)
13 (54.2%)
0/13 (0%)
11 (45.8%)
0/11 (0%)
2 (8.3%)
0/2 (0%)
20 (83.3%)
6/20 (30.0%)
1 (4.2%)
0/1 (0%)
13 (54.2%)
1/13 (7.7%)
Airway problem/tracheostomy/sleep apnoea (n=14)6 (42.9%)7 (50.0%)
0/7 (0%)
11 (78.6%)
0/11 (0%)
9 (64.3%)
0/9 (0%)
3 (21.4%)
1/3 (33.3%)
9 (64.3%)
2/9 (22.2%)
1 (7.1%)
0/1 (0%)
11 (78.6%)
3/11 (27.3%)
Feeding/swallowing difficulties (n=28)9 (32.1%)18 (64.3%)
0/18 (0%)
17 (60.7%)
0/17 (0%)
16 (57.1%)
0/16 (0%)
1 (3.6%)
0/1 (0%)
20 (71.4%)
2/10 (20.0%)
2 (7.1%)
0/2 (0%)
23 (82.1%)
7/23 (30.4%)
Hepatomegaly, abnormal liver function tests, splenomegaly or other features suggestive of inborn error of metabolism (n=12)3 (25.0%)9 (75.0%)
0/9 (0%)
12 (100%)
0/12 (0%)
10 (83.3%)
0/10 (0%)
4 (25.0%)
0/4 (0%)
7 (58.3%)
1/7 (14.3%)
2 (15.4%)
0/2 (0%)
12 (100%)
0/12 (0%)
Kidney, urinary tract abnormalities (n=17)6 (35.3%)9 (52.9%)
0/9 (0%)
12 (70.6%)
0/12 (0%)
9 (52.9%)
0/9 (0%)
5 (29.4%)
0/5 (0%)
11 (64.7%)
2/11 (18.2%)
1 (5.9%)
0/1 (0%)
12 (70.6%)
3/12 (25.0%)
Poor growth/failure to thrive/short stature (n=61)22 (36.1%)46 (75.4%)
0/46 (0%)
39 (63.9%)
1/39 (2.6%)
31 (50.8%)
2/31 (6.5%)
12 (19.7%)
0/12 (0%)
44 (72.1%)
5/44 (11.4%)
10 (16.4%)
0/10 (0%)
39 (63.9%)
14/39 (35.9%)
Obesity (n=17)2 (11.8%)12 (70.6%)
0/12 (0%)
9 (52.9%)
0/9 (0%)
7 (41.2%)
0/7 (0%)
1 (5.9%)
0/1 (0%)
9 (52.9%)
1/9 (11.1%)
1 (5.9%)
0/1 (0%)
7 (41.2%)
0/7 (0%)
Skeletal/rheumatological disorder (n=16)9 (56.3%)9 (56.3%)
0/9 (0%)
9 (56.3%)
0/9 (0%)
6 (37.5%)
0/6 (0%)
3 (18.8%)
0/3 (0%)
12 (75.0%)
3/12 (25.0%)
2 (12.5%)
0/2 (0%)
14 (87.5%)
6/14 (42.9%)
Features suggestive of ASD (n=99)13 (13.1%)62 (62.6%)
0/62 (0%)
54 (54.5%)
0/54 (0%)
44 (44.4%)
0/44 (0%)
19 (19.2%)
1/19 (5.3%)
55 (55.6%)
4/55 (7.3%)
26 (26.3%)
0/26 (0%)
42 (42.4%)
4/42 (9.5%)
Concerns about attention (n=14)2 (14.3%)9 (64.3%)
0/9 (0%)
5 (35.7%)
0/5 (0%)
2 (14.3%)
0/2 (0%)
3 (21.4%)
0/3 (0%)
8 (57.1%)
1/8 (12.5%)
3 (21.4%)
0/3 (0%)
8 (57.1%)
1/8 (12.5%)
Antenatal concerns for example, hydrops, alcohol or drug use (n=24)10 (41.7%)15 (62.5%)
1/15 (6.7%)
12 (50.0%)
0/12 (0%)
8 (33.3%)
0/8 (0%)
4 (16.7%)
0/4 (0%)
17 (70.8%)
2/17 (11.8%)
4 (16.7%)
0/4 (0%)
16 (66.7%)
5/16 (31.3%)
Ex-preterm (but not felt to explain EDI) (n=59)13 (22.0%)39 (66.1%)
1/39 (2.6%)
34 (57.6%)
0/34 (0%)
22 (37.3%)
1/22 (4.5%)
11 (18.6%)
0/11 (0%)
33 (55.9%)
2/33 (6.1%)
5 (8.5%)
0/5 (0%)
28 (47.5%)
5/28 (17.9%)
  • ASD, autistic spectrum disorder; EDI, early developmental impairment; LD, learning disabilities; TFT, thyroid function test; .