Table 1 Phenotypic information and SHOX testing results for the nine families from this study
Proband | Referral centre | Proband details | Inheritance | Variant type | Variant size | |
|---|---|---|---|---|---|---|
Minimum | Maximum | |||||
Patient 1 | Paediatric endocrinology | 14-year-old female of Bangladeshi origin with ISS (height 141.7 cm; − 2.84 SD) and poor weight gain. Karyotyping, thyroid function, coeliac screen, full blood count, renal liver, bone profile and IGF1 were all normal | Unknown | Deletion of CNE-3 | X:449,110–498,890 | X:446,596–499,211 |
Patient 2 | Paediatric endocrinology | 7-year-old British Caucasian male with ISS (height 106.4 cm; − 3.27 SD). Skeletal survey, investigations for bone age, IGF1 and growth hormone provocation were all normal. His mother’s height is 160.8 cm (− 0.36 SD) | Maternal | Deletion of CNE-3 | Not applicable (sequenced) | X:458,739–460,800 |
Patient 3 | Clinical genetics | 5-year-old female with “a diagnosis of ISS”. The family did not consent to further assessment | Unknown | Deletion | Not applicable (sequenced) | X:579,123–580,912 |
Patient 4 | Paediatric endocrinology | 12-year-old British Caucasian female. Normal weight, length, hearing, vision and development at birth. Had ISS at age 5 (height < − 2 SD) but height at age 12 was 138.5 cm (− 1.87 SD). IGF1, karyotype and celiac investigations were all normal. Mother’s height is 157 cm (− 1.13 SD). Her 7-year-old brother has a height of 119 cm (− 1.22 SD) | Maternal, and also present in her brother | Triplication of X:970,000 | X:907,457–1,232,802 | X:899,389–1,327,688 |
Patient 5 | Paediatrics | 6-year-old female of South Asian origin with ISS (height 101.2 cm; − 2.48 SD) | Unknown | Duplication of CNE-5 | X:307,417–399,032 | X:300,000–400,000 |
Patient 6 | Paediatrics | 8-year-old British Caucasian female. Short stature compared to parental heights (121.1 cm; − 1.1 SD). Karyotyping, growth hormone stimulation, cortisol, prolactin, IGF1, IGFBP-3 and parathyroid hormone investigations were all normal. Her bone age was 1.5 years delayed | Unknown | Duplication of CNE-5 | X:387,593–446,596 | X:380,503–449,110 |
Patient 7 | Paediatric endocrinology | 11-year-old Caucasian male of Eastern European origin with ISS (132.9 cm; − 2.03 SD). His bone age was < 1 year delayed. Baseline endocrinology tests were normal | Unknown | Duplication of X:970,000 | X:845,095–1,110,229 | X:836,131–1,113,655 |
Patient 8 | Clinical genetics | 9-year-old Caucasian female of mixed British and South American origin with LWD (height 124.5 cm; − 1.53 SD, and bilateral Madelung deformities with a typical thickened Vicker's ligament). Father has LWD (bilateral Madelung deformities, height 175 cm; − 0.21 SD) as does her 11 year-old sister (bilateral Madelung deformities, height 140 cm; − 1 SD) | Both paternal, and both also present in her sister | Duplication | X:694,790–694,862 | X:675,012–714,223 |
Duplication of ZED and CNE9 | X:809,260–963,755 | X:781,231–970,703 | ||||
Patient 9 | Paediatric endocrinology | 4-year-old Caucasian female of Central European origin with ISS (height 98.1 cm; − 2 SD). Karyotype, glucose, cortisol and somatotropin investigations were all normal. Her bone age was delayed by 1 year and 3 months. Her father has a height of 175 cm (− 0.2 SD) and her paternal grandmother has a height of 170 cm (+ 1 SD) | Paternal, and also present in her paternal grandmother | Duplication of X:970,000 | X:963,670–1,401,665 | X:899,389–1,471,351 |