Table 1. Open in new tab Clinical...

Patient No.	Sex	Age, y	Patient`s Height (SDS)	Shorter Parent`s Height (SDS)	IGF-1 (SDS)	Stimulated GH, μg/L	Birth Weight (SDS)	Birth Length (SDS)	Additional Phenotypic Features	Gene	Mutation Status	Transcript Variant	Protein Variant	Parents Available for Genetic Testing	Conclusion
SGA only – 5/8 (62.5%) with P/LP variant
1	F	10	−4.32	−3.54	−1.68	11.0	−1.64	−3.05	—	COL11A1	M/n	c.2921C>A	p.Pro974Gln	Yes	Likely pathogenic
2	M	14	−4.10	−2.89	−3.68	10.0	−1.64	−2.39	Central hypothyroidism	TRHR	M/M	c.392T>C	p.Ile131Thr	Yes	Likely pathogenic (16)
3	M	12	−3.49	−3.00	−0.26	11.5	−3.01	−3.87	—	THRA	M/n	c.455G>A	p.Arg152Gln	Yes	Uncertain significance
4	M	10	−3.42	−3.03	−0.98	10.2	−1.62	−3.26	Advanced bone age (+1.9 years)	IHH	M/n	c.857C>T	p.Pro286Leu	No	Uncertain significance
5	M	9	−3.34	−2.67	−0.92	NA	−2.13	−3.52	—	COL9A2	M/n	c.1834G>A	p.Gly612Arg	Yes	Benign
6	M	16	−3.06	−2.75	0.16	19.3	−2.39	−2.57	Scoliosis	COL11A1	M/n	c.1543C>G	p.Gln515Glu	Yes	Likely pathogenic
7	M	10	−2.92	−3.30	−0.63	29.7	−1.35	−2.13	—	IGF1R	M/n	c.158C>T	p.Thr53Met	Yes	Likely pathogenic
8	F	11	−2.76	−2.75	−1.04	NA	−2.56	−4.14	Frequent OMA, genua valga, advanced bone age (+3.4 y)	COL2A1	M₁/M₂	c.410G>A / c.3106C>G	p.Arg137His/ p.Arg1036Gly	Yes	Likely pathogenic (6) / Likely pathogenic
GHD only – 4/9 (44.4%) with P/LP variant
9	M	14	−4.95	−2.89	−2.48	7.22	−0.94	−1.78	Minor stigmata, bilateral cryptorchidism	IGFALS	M/n	c.860C>T	p.Pro287Leu	No	Uncertain significance (17)
10	M	8	−4.48	−2.73	−1.11	6.36	−1.06	−1.75	B-cell immunity disorder, skin problems (hyperkeratosis, alopecia), corneal ulceration	MBTPS2	M/-	c.1538T>C	p.Leu513Pro	Yes	Likely pathogenic (19)
PIK3CD	M/n	c.1775T>C	p.Val952Ala	Yes	Uncertain significance
11	M	7	−4.37	−2.89	−1.86	9.40	−0.56	−1.04	Limb shortening	FGFR3	M/n	c.1612A>G	p.Ile538Val	Yes	Likely pathogenic (18)
12	F	8	−3.50	−2.60	−1.57	2.50	0.04	−0.95	Limb shortening	HSPG2	M/n	c.8044C>T	p.Arg2682Trp	Yes	Benign
13	M	13	−3.10	−2.59	−1.91	5.92	−0.85	−0.65	—	PAX6	M/n	c.13C>G c.392C>G	p.His5Asp p.Ala131Gly	Yes	Benign
14	M	5	−3.06	−3.86	−2.18	8.34	−1.94	−1.42	—	HMGA2	M/n	c.223C>T	p.Arg75Trp	Yes	Likely pathogenic
15	M	9	−3.04	−2.75	−1.82	6.06	−1.57	−1.68	Minor stigmata	IGFALS	M/n	c.589C>T	p.Arg197Cys	Yes	Pathogenic
IHH	M/n	c.1169G>A	p.Arg390His	Yes	Uncertain significance
16	M	8	−2.75	−2.75	−1.23	7.79	−1.02	−1.35	—	IGFALS	M/n	c.1195G>A	p.Gly399Arg	No	Uncertain significance
17	M	12	−2.53	−2.75	−1.28	8.30	−1.60	−0.65	—	GH1	M/n	c.478C>T	p.Arg160Trp	Yes	Benign
FBN1	M/n	c.902G>T	p.Gly301Val	Yes	Benign
SGA + GHD – 3/11 (27.3%) with P/LP variant
18	M	9	−4.17	−3.81	−1.98	5.18	−1.95	−3.09	Hypospadia, minor stigmata	HSPG2	M/n	c.12874G>A	p.Glu4292Lys	Yes	Benign
19	F	8	−3.82	−4.03	−0.44	7.77	−0.84	−2.14	Limb shortening	GLI2 GLI2	M/n	c.4332G>A c.4333C>T	p.Met1444Ile p.Leu1445Phe	Yes	Benign
20	M	6	−3.61	−3.25	−1.14	6.4	−2.16	−3.12	—	—	—	—	—	—	No variant found
21	M	14	−3.47	−2.89	−1.63	8.39	−2.39	−3.00	Microcephaly	COL2A1	M/n	c.3106C>G	p.Arg1036Gly	Yes	Likely pathogenic
22	M	8	−3.28	−2.89	−1.83	6.37	−0.60	−2.39	—	—	—	—	—	—	No variant found
23	M	13	−3.26	−2.81	−1.22	7.44	−2.18	−2.22	—	SHH	M/n	c.424G>A	p.Glu142Lys	Yes	Benign
24	F	14	−3.18	−2.75	−2.1	7.15	−2.56	−3.13	Lower-limb shortening, minor stigmata	GHSR	M/n	c.526G>A	p.Gly176Arg	Yes	Pathogenic
25	M	8	−2.84	−2.87	−0.98	5.91	−2.59	−2.83	Minor stigmata	COL10A1	M/n	c.1581G>C	p.Lys527Asn	Yes	Likely benign
26	F	12	−2.76	−2.89	−3.45	3.62	−2.78	−1.23	Shorter trunk, longer limbs, blue sclera, teeth decay, ectopic posterior pituitary	—	—	—	—	—	No variant found
27	M	10	−2.70	−2.75	−0.66	3.44	−2.39	−3.43	—	EXT2	M/n	c.2034G>C	p.Lys678Asn	No	Uncertain significance
28	M	5	−2.62	−3.60	−2.25	6.99	−1.40	−2.22	—	FLNB	M/n	c.1601T>G	p.Ile534Ser	Yes	Likely pathogenic

Patient No.

Sex

Age, y

Patient`s Height (SDS)

Shorter Parent`s Height (SDS)

IGF-1 (SDS)

Stimulated GH, μg/L

Birth Weight (SDS)

Birth Length (SDS)

Additional Phenotypic Features

Gene

Mutation Status

Transcript Variant

Protein Variant

Parents Available for Genetic Testing

Conclusion

SGA only – 5/8 (62.5%) with P/LP variant

−4.32

−3.54

−1.68

11.0

−1.64

−3.05

—

COL11A1

M/n

c.2921C>A

p.Pro974Gln

Yes

Likely pathogenic

−4.10

−2.89

−3.68

10.0

−1.64

−2.39

Central hypothyroidism

TRHR

M/M

c.392T>C

p.Ile131Thr

Yes

Likely pathogenic (16)

−3.49

−3.00

−0.26

11.5

−3.01

−3.87

—

THRA

M/n

c.455G>A

p.Arg152Gln

Yes

Uncertain significance

−3.42

−3.03

−0.98

10.2

−1.62

−3.26

Advanced bone age (+1.9 years)

IHH

M/n

c.857C>T

p.Pro286Leu

Uncertain significance

−3.34

−2.67

−0.92

−2.13

−3.52

—

COL9A2

M/n

c.1834G>A

p.Gly612Arg

Yes

Benign

−3.06

−2.75

0.16

19.3

−2.39

−2.57

Scoliosis

COL11A1

M/n

c.1543C>G

p.Gln515Glu

Yes

Likely pathogenic

−2.92

−3.30

−0.63

29.7

−1.35

−2.13

—

IGF1R

M/n

c.158C>T

p.Thr53Met

Yes

Likely pathogenic

−2.76

−2.75

−1.04

−2.56

−4.14

Frequent OMA, genua valga, advanced bone age (+3.4 y)

COL2A1

M₁/M₂

c.410G>A / c.3106C>G

p.Arg137His/ p.Arg1036Gly

Yes

Likely pathogenic (6) / Likely pathogenic

GHD only – 4/9 (44.4%) with P/LP variant

−4.95

−2.89

−2.48

7.22

−0.94

−1.78

Minor stigmata, bilateral cryptorchidism

IGFALS

M/n

c.860C>T

p.Pro287Leu

Uncertain significance (17)

−4.48

−2.73

−1.11

6.36

−1.06

−1.75

B-cell immunity disorder, skin problems (hyperkeratosis, alopecia), corneal ulceration

MBTPS2

M/-

c.1538T>C

p.Leu513Pro

Yes

Likely pathogenic (19)

PIK3CD

M/n

c.1775T>C

p.Val952Ala

Yes

Uncertain significance

−4.37

−2.89

−1.86

9.40

−0.56

−1.04

Limb shortening

FGFR3

M/n

c.1612A>G

p.Ile538Val

Yes

Likely pathogenic (18)

−3.50

−2.60

−1.57

2.50

0.04

−0.95

Limb shortening

HSPG2

M/n

c.8044C>T

p.Arg2682Trp

Yes

Benign

−3.10

−2.59

−1.91

5.92

−0.85

−0.65

—

PAX6

M/n

c.13C>G c.392C>G

p.His5Asp p.Ala131Gly

Yes

Benign

−3.06

−3.86

−2.18

8.34

−1.94

−1.42

—

HMGA2

M/n

c.223C>T

p.Arg75Trp

Yes

Likely pathogenic

−3.04

−2.75

−1.82

6.06

−1.57

−1.68

Minor stigmata

IGFALS

M/n

c.589C>T

p.Arg197Cys

Yes

Pathogenic

IHH

M/n

c.1169G>A

p.Arg390His

Yes

Uncertain significance

−2.75

−1.23

7.79

−1.02

−1.35

—

IGFALS

M/n

c.1195G>A

p.Gly399Arg

Uncertain significance

−2.53

−2.75

−1.28

8.30

−1.60

−0.65

—

GH1

M/n

c.478C>T

p.Arg160Trp

Yes

Benign

FBN1

M/n

c.902G>T

p.Gly301Val

Yes

Benign

SGA + GHD – 3/11 (27.3%) with P/LP variant

−4.17

−3.81

−1.98

5.18

−1.95

−3.09

Hypospadia, minor stigmata

HSPG2

M/n

c.12874G>A

p.Glu4292Lys

Yes

Benign

−3.82

−4.03

−0.44

7.77

−0.84

−2.14

Limb shortening

GLI2 GLI2

M/n

c.4332G>A c.4333C>T

p.Met1444Ile p.Leu1445Phe

Yes

Benign

−3.61

−3.25

−1.14

6.4

−2.16

−3.12

—

No variant found

−3.47

−2.89

−1.63

8.39

−2.39

−3.00

Microcephaly

COL2A1

M/n

c.3106C>G

p.Arg1036Gly

Yes

Likely pathogenic

−3.28

−2.89

−1.83

6.37

−0.60

−2.39

—

No variant found

−3.26

−2.81

−1.22

7.44

−2.18

−2.22

—

SHH

M/n

c.424G>A

p.Glu142Lys

Yes

Benign

−3.18

−2.75

−2.1

7.15

−2.56

−3.13

Lower-limb shortening, minor stigmata

GHSR

M/n

c.526G>A

p.Gly176Arg

Yes

Pathogenic

−2.84

−2.87

−0.98

5.91

−2.59

−2.83

Minor stigmata

COL10A1

M/n

c.1581G>C

p.Lys527Asn

Yes

Likely benign

−2.76

−2.89

−3.45

3.62

−2.78

−1.23

Shorter trunk, longer limbs, blue sclera, teeth decay, ectopic posterior pituitary

—

No variant found

−2.70

−2.75

−0.66

3.44

−2.39

−3.43

—

EXT2

M/n

c.2034G>C

p.Lys678Asn

Uncertain significance

−2.62

−3.60

−2.25

6.99

−1.40

−2.22

—

FLNB

M/n

c.1601T>G

p.Ile534Ser

Yes

Likely pathogenic

Patient No.	Sex	Age, y	Patient`s Height (SDS)	Shorter Parent`s Height (SDS)	IGF-1 (SDS)	Stimulated GH, μg/L	Birth Weight (SDS)	Birth Length (SDS)	Additional Phenotypic Features	Gene	Mutation Status	Transcript Variant	Protein Variant	Parents Available for Genetic Testing	Conclusion
SGA only – 5/8 (62.5%) with P/LP variant
1	F	10	−4.32	−3.54	−1.68	11.0	−1.64	−3.05	—	COL11A1	M/n	c.2921C>A	p.Pro974Gln	Yes	Likely pathogenic
2	M	14	−4.10	−2.89	−3.68	10.0	−1.64	−2.39	Central hypothyroidism	TRHR	M/M	c.392T>C	p.Ile131Thr	Yes	Likely pathogenic (16)
3	M	12	−3.49	−3.00	−0.26	11.5	−3.01	−3.87	—	THRA	M/n	c.455G>A	p.Arg152Gln	Yes	Uncertain significance
4	M	10	−3.42	−3.03	−0.98	10.2	−1.62	−3.26	Advanced bone age (+1.9 years)	IHH	M/n	c.857C>T	p.Pro286Leu	No	Uncertain significance
5	M	9	−3.34	−2.67	−0.92	NA	−2.13	−3.52	—	COL9A2	M/n	c.1834G>A	p.Gly612Arg	Yes	Benign
6	M	16	−3.06	−2.75	0.16	19.3	−2.39	−2.57	Scoliosis	COL11A1	M/n	c.1543C>G	p.Gln515Glu	Yes	Likely pathogenic
7	M	10	−2.92	−3.30	−0.63	29.7	−1.35	−2.13	—	IGF1R	M/n	c.158C>T	p.Thr53Met	Yes	Likely pathogenic
8	F	11	−2.76	−2.75	−1.04	NA	−2.56	−4.14	Frequent OMA, genua valga, advanced bone age (+3.4 y)	COL2A1	M₁/M₂	c.410G>A / c.3106C>G	p.Arg137His/ p.Arg1036Gly	Yes	Likely pathogenic (6) / Likely pathogenic
GHD only – 4/9 (44.4%) with P/LP variant
9	M	14	−4.95	−2.89	−2.48	7.22	−0.94	−1.78	Minor stigmata, bilateral cryptorchidism	IGFALS	M/n	c.860C>T	p.Pro287Leu	No	Uncertain significance (17)
10	M	8	−4.48	−2.73	−1.11	6.36	−1.06	−1.75	B-cell immunity disorder, skin problems (hyperkeratosis, alopecia), corneal ulceration	MBTPS2	M/-	c.1538T>C	p.Leu513Pro	Yes	Likely pathogenic (19)
PIK3CD	M/n	c.1775T>C	p.Val952Ala	Yes	Uncertain significance
11	M	7	−4.37	−2.89	−1.86	9.40	−0.56	−1.04	Limb shortening	FGFR3	M/n	c.1612A>G	p.Ile538Val	Yes	Likely pathogenic (18)
12	F	8	−3.50	−2.60	−1.57	2.50	0.04	−0.95	Limb shortening	HSPG2	M/n	c.8044C>T	p.Arg2682Trp	Yes	Benign
13	M	13	−3.10	−2.59	−1.91	5.92	−0.85	−0.65	—	PAX6	M/n	c.13C>G c.392C>G	p.His5Asp p.Ala131Gly	Yes	Benign
14	M	5	−3.06	−3.86	−2.18	8.34	−1.94	−1.42	—	HMGA2	M/n	c.223C>T	p.Arg75Trp	Yes	Likely pathogenic
15	M	9	−3.04	−2.75	−1.82	6.06	−1.57	−1.68	Minor stigmata	IGFALS	M/n	c.589C>T	p.Arg197Cys	Yes	Pathogenic
IHH	M/n	c.1169G>A	p.Arg390His	Yes	Uncertain significance
16	M	8	−2.75	−2.75	−1.23	7.79	−1.02	−1.35	—	IGFALS	M/n	c.1195G>A	p.Gly399Arg	No	Uncertain significance
17	M	12	−2.53	−2.75	−1.28	8.30	−1.60	−0.65	—	GH1	M/n	c.478C>T	p.Arg160Trp	Yes	Benign
FBN1	M/n	c.902G>T	p.Gly301Val	Yes	Benign
SGA + GHD – 3/11 (27.3%) with P/LP variant
18	M	9	−4.17	−3.81	−1.98	5.18	−1.95	−3.09	Hypospadia, minor stigmata	HSPG2	M/n	c.12874G>A	p.Glu4292Lys	Yes	Benign
19	F	8	−3.82	−4.03	−0.44	7.77	−0.84	−2.14	Limb shortening	GLI2 GLI2	M/n	c.4332G>A c.4333C>T	p.Met1444Ile p.Leu1445Phe	Yes	Benign
20	M	6	−3.61	−3.25	−1.14	6.4	−2.16	−3.12	—	—	—	—	—	—	No variant found
21	M	14	−3.47	−2.89	−1.63	8.39	−2.39	−3.00	Microcephaly	COL2A1	M/n	c.3106C>G	p.Arg1036Gly	Yes	Likely pathogenic
22	M	8	−3.28	−2.89	−1.83	6.37	−0.60	−2.39	—	—	—	—	—	—	No variant found
23	M	13	−3.26	−2.81	−1.22	7.44	−2.18	−2.22	—	SHH	M/n	c.424G>A	p.Glu142Lys	Yes	Benign
24	F	14	−3.18	−2.75	−2.1	7.15	−2.56	−3.13	Lower-limb shortening, minor stigmata	GHSR	M/n	c.526G>A	p.Gly176Arg	Yes	Pathogenic
25	M	8	−2.84	−2.87	−0.98	5.91	−2.59	−2.83	Minor stigmata	COL10A1	M/n	c.1581G>C	p.Lys527Asn	Yes	Likely benign
26	F	12	−2.76	−2.89	−3.45	3.62	−2.78	−1.23	Shorter trunk, longer limbs, blue sclera, teeth decay, ectopic posterior pituitary	—	—	—	—	—	No variant found
27	M	10	−2.70	−2.75	−0.66	3.44	−2.39	−3.43	—	EXT2	M/n	c.2034G>C	p.Lys678Asn	No	Uncertain significance
28	M	5	−2.62	−3.60	−2.25	6.99	−1.40	−2.22	—	FLNB	M/n	c.1601T>G	p.Ile534Ser	Yes	Likely pathogenic

Patient No.

Sex

Age, y

Patient`s Height (SDS)

Shorter Parent`s Height (SDS)

IGF-1 (SDS)

Stimulated GH, μg/L

Birth Weight (SDS)

Birth Length (SDS)

Additional Phenotypic Features

Gene

Mutation Status

Transcript Variant

Protein Variant

Parents Available for Genetic Testing

Conclusion

SGA only – 5/8 (62.5%) with P/LP variant

−4.32

−3.54

−1.68

11.0

−1.64

−3.05

—

COL11A1

M/n

c.2921C>A

p.Pro974Gln

Yes

Likely pathogenic

−4.10

−2.89

−3.68

10.0

−1.64

−2.39

Central hypothyroidism

TRHR

M/M

c.392T>C

p.Ile131Thr

Yes

Likely pathogenic (16)

−3.49

−3.00

−0.26

11.5

−3.01

−3.87

—

THRA

M/n

c.455G>A

p.Arg152Gln

Yes

Uncertain significance

−3.42

−3.03

−0.98

10.2

−1.62

−3.26

Advanced bone age (+1.9 years)

IHH

M/n

c.857C>T

p.Pro286Leu

Uncertain significance

−3.34

−2.67

−0.92

−2.13

−3.52

—

COL9A2

M/n

c.1834G>A

p.Gly612Arg

Yes

Benign

−3.06

−2.75

0.16

19.3

−2.39

−2.57

Scoliosis

COL11A1

M/n

c.1543C>G

p.Gln515Glu

Yes

Likely pathogenic

−2.92

−3.30

−0.63

29.7

−1.35

−2.13

—

IGF1R

M/n

c.158C>T

p.Thr53Met

Yes

Likely pathogenic

−2.76

−2.75

−1.04

−2.56

−4.14

Frequent OMA, genua valga, advanced bone age (+3.4 y)

COL2A1

M₁/M₂

c.410G>A / c.3106C>G

p.Arg137His/ p.Arg1036Gly

Yes

Likely pathogenic (6) / Likely pathogenic

GHD only – 4/9 (44.4%) with P/LP variant

−4.95

−2.89

−2.48

7.22

−0.94

−1.78

Minor stigmata, bilateral cryptorchidism

IGFALS

M/n

c.860C>T

p.Pro287Leu

Uncertain significance (17)

−4.48

−2.73

−1.11

6.36

−1.06

−1.75

B-cell immunity disorder, skin problems (hyperkeratosis, alopecia), corneal ulceration

MBTPS2

M/-

c.1538T>C

p.Leu513Pro

Yes

Likely pathogenic (19)

PIK3CD

M/n

c.1775T>C

p.Val952Ala

Yes

Uncertain significance

−4.37

−2.89

−1.86

9.40

−0.56

−1.04

Limb shortening

FGFR3

M/n

c.1612A>G

p.Ile538Val

Yes

Likely pathogenic (18)

−3.50

−2.60

−1.57

2.50

0.04

−0.95

Limb shortening

HSPG2

M/n

c.8044C>T

p.Arg2682Trp

Yes

Benign

−3.10

−2.59

−1.91

5.92

−0.85

−0.65

—

PAX6

M/n

c.13C>G c.392C>G

p.His5Asp p.Ala131Gly

Yes

Benign

−3.06

−3.86

−2.18

8.34

−1.94

−1.42

—

HMGA2

M/n

c.223C>T

p.Arg75Trp

Yes

Likely pathogenic

−3.04

−2.75

−1.82

6.06

−1.57

−1.68

Minor stigmata

IGFALS

M/n

c.589C>T

p.Arg197Cys

Yes

Pathogenic

IHH

M/n

c.1169G>A

p.Arg390His

Yes

Uncertain significance

−2.75

−1.23

7.79

−1.02

−1.35

—

IGFALS

M/n

c.1195G>A

p.Gly399Arg

Uncertain significance

−2.53

−2.75

−1.28

8.30

−1.60

−0.65

—

GH1

M/n

c.478C>T

p.Arg160Trp

Yes

Benign

FBN1

M/n

c.902G>T

p.Gly301Val

Yes

Benign

SGA + GHD – 3/11 (27.3%) with P/LP variant

−4.17

−3.81

−1.98

5.18

−1.95

−3.09

Hypospadia, minor stigmata

HSPG2

M/n

c.12874G>A

p.Glu4292Lys

Yes

Benign

−3.82

−4.03

−0.44

7.77

−0.84

−2.14

Limb shortening

GLI2 GLI2

M/n

c.4332G>A c.4333C>T

p.Met1444Ile p.Leu1445Phe

Yes

Benign

−3.61

−3.25

−1.14

6.4

−2.16

−3.12

—

No variant found

−3.47

−2.89

−1.63

8.39

−2.39

−3.00

Microcephaly

COL2A1

M/n

c.3106C>G

p.Arg1036Gly

Yes

Likely pathogenic

−3.28

−2.89

−1.83

6.37

−0.60

−2.39

—

No variant found

−3.26

−2.81

−1.22

7.44

−2.18

−2.22

—

SHH

M/n

c.424G>A

p.Glu142Lys

Yes

Benign

−3.18

−2.75

−2.1

7.15

−2.56

−3.13

Lower-limb shortening, minor stigmata

GHSR

M/n

c.526G>A

p.Gly176Arg

Yes

Pathogenic

−2.84

−2.87

−0.98

5.91

−2.59

−2.83

Minor stigmata

COL10A1

M/n

c.1581G>C

p.Lys527Asn

Yes

Likely benign

−2.76

−2.89

−3.45

3.62

−2.78

−1.23

Shorter trunk, longer limbs, blue sclera, teeth decay, ectopic posterior pituitary

—

No variant found

−2.70

−2.75

−0.66

3.44

−2.39

−3.43

—

EXT2

M/n

c.2034G>C

p.Lys678Asn

Uncertain significance

−2.62

−3.60

−2.25

6.99

−1.40

−2.22

—

FLNB

M/n

c.1601T>G

p.Ile534Ser

Yes

Likely pathogenic

Table 1.

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Clinical Features and Genetic Results of Children With Severe FSS Examined by WES

Patient No.	Sex	Age, y	Patient`s Height (SDS)	Shorter Parent`s Height (SDS)	IGF-1 (SDS)	Stimulated GH, μg/L	Birth Weight (SDS)	Birth Length (SDS)	Additional Phenotypic Features	Gene	Mutation Status	Transcript Variant	Protein Variant	Parents Available for Genetic Testing	Conclusion
SGA only – 5/8 (62.5%) with P/LP variant
1	F	10	−4.32	−3.54	−1.68	11.0	−1.64	−3.05	—	COL11A1	M/n	c.2921C>A	p.Pro974Gln	Yes	Likely pathogenic
2	M	14	−4.10	−2.89	−3.68	10.0	−1.64	−2.39	Central hypothyroidism	TRHR	M/M	c.392T>C	p.Ile131Thr	Yes	Likely pathogenic (16)
3	M	12	−3.49	−3.00	−0.26	11.5	−3.01	−3.87	—	THRA	M/n	c.455G>A	p.Arg152Gln	Yes	Uncertain significance
4	M	10	−3.42	−3.03	−0.98	10.2	−1.62	−3.26	Advanced bone age (+1.9 years)	IHH	M/n	c.857C>T	p.Pro286Leu	No	Uncertain significance
5	M	9	−3.34	−2.67	−0.92	NA	−2.13	−3.52	—	COL9A2	M/n	c.1834G>A	p.Gly612Arg	Yes	Benign
6	M	16	−3.06	−2.75	0.16	19.3	−2.39	−2.57	Scoliosis	COL11A1	M/n	c.1543C>G	p.Gln515Glu	Yes	Likely pathogenic
7	M	10	−2.92	−3.30	−0.63	29.7	−1.35	−2.13	—	IGF1R	M/n	c.158C>T	p.Thr53Met	Yes	Likely pathogenic
8	F	11	−2.76	−2.75	−1.04	NA	−2.56	−4.14	Frequent OMA, genua valga, advanced bone age (+3.4 y)	COL2A1	M₁/M₂	c.410G>A / c.3106C>G	p.Arg137His/ p.Arg1036Gly	Yes	Likely pathogenic (6) / Likely pathogenic
GHD only – 4/9 (44.4%) with P/LP variant
9	M	14	−4.95	−2.89	−2.48	7.22	−0.94	−1.78	Minor stigmata, bilateral cryptorchidism	IGFALS	M/n	c.860C>T	p.Pro287Leu	No	Uncertain significance (17)
10	M	8	−4.48	−2.73	−1.11	6.36	−1.06	−1.75	B-cell immunity disorder, skin problems (hyperkeratosis, alopecia), corneal ulceration	MBTPS2	M/-	c.1538T>C	p.Leu513Pro	Yes	Likely pathogenic (19)
10	M	8	−4.48	−2.73	−1.11	6.36	−1.06	−1.75		PIK3CD	M/n	c.1775T>C	p.Val952Ala	Yes	Uncertain significance
11	M	7	−4.37	−2.89	−1.86	9.40	−0.56	−1.04	Limb shortening	FGFR3	M/n	c.1612A>G	p.Ile538Val	Yes	Likely pathogenic (18)
12	F	8	−3.50	−2.60	−1.57	2.50	0.04	−0.95	Limb shortening	HSPG2	M/n	c.8044C>T	p.Arg2682Trp	Yes	Benign
13	M	13	−3.10	−2.59	−1.91	5.92	−0.85	−0.65	—	PAX6	M/n	c.13C>G c.392C>G	p.His5Asp p.Ala131Gly	Yes	Benign
14	M	5	−3.06	−3.86	−2.18	8.34	−1.94	−1.42	—	HMGA2	M/n	c.223C>T	p.Arg75Trp	Yes	Likely pathogenic
15	M	9	−3.04	−2.75	−1.82	6.06	−1.57	−1.68	Minor stigmata	IGFALS	M/n	c.589C>T	p.Arg197Cys	Yes	Pathogenic
15	M	9	−3.04	−2.75	−1.82	6.06	−1.57	−1.68	Minor stigmata	IHH	M/n	c.1169G>A	p.Arg390His	Yes	Uncertain significance
16	M	8	−2.75	−2.75	−1.23	7.79	−1.02	−1.35	—	IGFALS	M/n	c.1195G>A	p.Gly399Arg	No	Uncertain significance
17	M	12	−2.53	−2.75	−1.28	8.30	−1.60	−0.65	—	GH1	M/n	c.478C>T	p.Arg160Trp	Yes	Benign
17	M	12	−2.53	−2.75	−1.28	8.30	−1.60	−0.65	—	FBN1	M/n	c.902G>T	p.Gly301Val	Yes	Benign
SGA + GHD – 3/11 (27.3%) with P/LP variant
18	M	9	−4.17	−3.81	−1.98	5.18	−1.95	−3.09	Hypospadia, minor stigmata	HSPG2	M/n	c.12874G>A	p.Glu4292Lys	Yes	Benign
19	F	8	−3.82	−4.03	−0.44	7.77	−0.84	−2.14	Limb shortening	GLI2 GLI2	M/n	c.4332G>A c.4333C>T	p.Met1444Ile p.Leu1445Phe	Yes	Benign
20	M	6	−3.61	−3.25	−1.14	6.4	−2.16	−3.12	—	—	—	—	—	—	No variant found
21	M	14	−3.47	−2.89	−1.63	8.39	−2.39	−3.00	Microcephaly	COL2A1	M/n	c.3106C>G	p.Arg1036Gly	Yes	Likely pathogenic
22	M	8	−3.28	−2.89	−1.83	6.37	−0.60	−2.39	—	—	—	—	—	—	No variant found
23	M	13	−3.26	−2.81	−1.22	7.44	−2.18	−2.22	—	SHH	M/n	c.424G>A	p.Glu142Lys	Yes	Benign
24	F	14	−3.18	−2.75	−2.1	7.15	−2.56	−3.13	Lower-limb shortening, minor stigmata	GHSR	M/n	c.526G>A	p.Gly176Arg	Yes	Pathogenic
25	M	8	−2.84	−2.87	−0.98	5.91	−2.59	−2.83	Minor stigmata	COL10A1	M/n	c.1581G>C	p.Lys527Asn	Yes	Likely benign
26	F	12	−2.76	−2.89	−3.45	3.62	−2.78	−1.23	Shorter trunk, longer limbs, blue sclera, teeth decay, ectopic posterior pituitary	—	—	—	—	—	No variant found
27	M	10	−2.70	−2.75	−0.66	3.44	−2.39	−3.43	—	EXT2	M/n	c.2034G>C	p.Lys678Asn	No	Uncertain significance
28	M	5	−2.62	−3.60	−2.25	6.99	−1.40	−2.22	—	FLNB	M/n	c.1601T>G	p.Ile534Ser	Yes	Likely pathogenic

Patient No.	Sex	Age, y	Patient`s Height (SDS)	Shorter Parent`s Height (SDS)	IGF-1 (SDS)	Stimulated GH, μg/L	Birth Weight (SDS)	Birth Length (SDS)	Additional Phenotypic Features	Gene	Mutation Status	Transcript Variant	Protein Variant	Parents Available for Genetic Testing	Conclusion
SGA only – 5/8 (62.5%) with P/LP variant
1	F	10	−4.32	−3.54	−1.68	11.0	−1.64	−3.05	—	COL11A1	M/n	c.2921C>A	p.Pro974Gln	Yes	Likely pathogenic
2	M	14	−4.10	−2.89	−3.68	10.0	−1.64	−2.39	Central hypothyroidism	TRHR	M/M	c.392T>C	p.Ile131Thr	Yes	Likely pathogenic (16)
3	M	12	−3.49	−3.00	−0.26	11.5	−3.01	−3.87	—	THRA	M/n	c.455G>A	p.Arg152Gln	Yes	Uncertain significance
4	M	10	−3.42	−3.03	−0.98	10.2	−1.62	−3.26	Advanced bone age (+1.9 years)	IHH	M/n	c.857C>T	p.Pro286Leu	No	Uncertain significance
5	M	9	−3.34	−2.67	−0.92	NA	−2.13	−3.52	—	COL9A2	M/n	c.1834G>A	p.Gly612Arg	Yes	Benign
6	M	16	−3.06	−2.75	0.16	19.3	−2.39	−2.57	Scoliosis	COL11A1	M/n	c.1543C>G	p.Gln515Glu	Yes	Likely pathogenic
7	M	10	−2.92	−3.30	−0.63	29.7	−1.35	−2.13	—	IGF1R	M/n	c.158C>T	p.Thr53Met	Yes	Likely pathogenic
8	F	11	−2.76	−2.75	−1.04	NA	−2.56	−4.14	Frequent OMA, genua valga, advanced bone age (+3.4 y)	COL2A1	M₁/M₂	c.410G>A / c.3106C>G	p.Arg137His/ p.Arg1036Gly	Yes	Likely pathogenic (6) / Likely pathogenic
GHD only – 4/9 (44.4%) with P/LP variant
9	M	14	−4.95	−2.89	−2.48	7.22	−0.94	−1.78	Minor stigmata, bilateral cryptorchidism	IGFALS	M/n	c.860C>T	p.Pro287Leu	No	Uncertain significance (17)
10	M	8	−4.48	−2.73	−1.11	6.36	−1.06	−1.75	B-cell immunity disorder, skin problems (hyperkeratosis, alopecia), corneal ulceration	MBTPS2	M/-	c.1538T>C	p.Leu513Pro	Yes	Likely pathogenic (19)
10	M	8	−4.48	−2.73	−1.11	6.36	−1.06	−1.75		PIK3CD	M/n	c.1775T>C	p.Val952Ala	Yes	Uncertain significance
11	M	7	−4.37	−2.89	−1.86	9.40	−0.56	−1.04	Limb shortening	FGFR3	M/n	c.1612A>G	p.Ile538Val	Yes	Likely pathogenic (18)
12	F	8	−3.50	−2.60	−1.57	2.50	0.04	−0.95	Limb shortening	HSPG2	M/n	c.8044C>T	p.Arg2682Trp	Yes	Benign
13	M	13	−3.10	−2.59	−1.91	5.92	−0.85	−0.65	—	PAX6	M/n	c.13C>G c.392C>G	p.His5Asp p.Ala131Gly	Yes	Benign
14	M	5	−3.06	−3.86	−2.18	8.34	−1.94	−1.42	—	HMGA2	M/n	c.223C>T	p.Arg75Trp	Yes	Likely pathogenic
15	M	9	−3.04	−2.75	−1.82	6.06	−1.57	−1.68	Minor stigmata	IGFALS	M/n	c.589C>T	p.Arg197Cys	Yes	Pathogenic
15	M	9	−3.04	−2.75	−1.82	6.06	−1.57	−1.68	Minor stigmata	IHH	M/n	c.1169G>A	p.Arg390His	Yes	Uncertain significance
16	M	8	−2.75	−2.75	−1.23	7.79	−1.02	−1.35	—	IGFALS	M/n	c.1195G>A	p.Gly399Arg	No	Uncertain significance
17	M	12	−2.53	−2.75	−1.28	8.30	−1.60	−0.65	—	GH1	M/n	c.478C>T	p.Arg160Trp	Yes	Benign
17	M	12	−2.53	−2.75	−1.28	8.30	−1.60	−0.65	—	FBN1	M/n	c.902G>T	p.Gly301Val	Yes	Benign
SGA + GHD – 3/11 (27.3%) with P/LP variant
18	M	9	−4.17	−3.81	−1.98	5.18	−1.95	−3.09	Hypospadia, minor stigmata	HSPG2	M/n	c.12874G>A	p.Glu4292Lys	Yes	Benign
19	F	8	−3.82	−4.03	−0.44	7.77	−0.84	−2.14	Limb shortening	GLI2 GLI2	M/n	c.4332G>A c.4333C>T	p.Met1444Ile p.Leu1445Phe	Yes	Benign
20	M	6	−3.61	−3.25	−1.14	6.4	−2.16	−3.12	—	—	—	—	—	—	No variant found
21	M	14	−3.47	−2.89	−1.63	8.39	−2.39	−3.00	Microcephaly	COL2A1	M/n	c.3106C>G	p.Arg1036Gly	Yes	Likely pathogenic
22	M	8	−3.28	−2.89	−1.83	6.37	−0.60	−2.39	—	—	—	—	—	—	No variant found
23	M	13	−3.26	−2.81	−1.22	7.44	−2.18	−2.22	—	SHH	M/n	c.424G>A	p.Glu142Lys	Yes	Benign
24	F	14	−3.18	−2.75	−2.1	7.15	−2.56	−3.13	Lower-limb shortening, minor stigmata	GHSR	M/n	c.526G>A	p.Gly176Arg	Yes	Pathogenic
25	M	8	−2.84	−2.87	−0.98	5.91	−2.59	−2.83	Minor stigmata	COL10A1	M/n	c.1581G>C	p.Lys527Asn	Yes	Likely benign
26	F	12	−2.76	−2.89	−3.45	3.62	−2.78	−1.23	Shorter trunk, longer limbs, blue sclera, teeth decay, ectopic posterior pituitary	—	—	—	—	—	No variant found
27	M	10	−2.70	−2.75	−0.66	3.44	−2.39	−3.43	—	EXT2	M/n	c.2034G>C	p.Lys678Asn	No	Uncertain significance
28	M	5	−2.62	−3.60	−2.25	6.99	−1.40	−2.22	—	FLNB	M/n	c.1601T>G	p.Ile534Ser	Yes	Likely pathogenic

Abbreviations: F, female; GHD, GH deficiency; LP, likely pathogenic; M, male; M/n, heterozygote; M/M, homozygote; M₁/M₂, compound heterozygote; M/-, hemizygote; OMA, otitis media acuta; P, pathogenic; SDS, SD score; SGA, small for gestational age.

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