The range of diagnoses identified in children found to have pathological causes for their short stature (‘pathological short stature’ group 1) (n=51)
| Diagnosis | Sex M:F | Age or mean age (range) | Clinical details |
| Primary growth failure (n=28) | |||
| Turner syndrome (n=1) | F | 13.9 | Mosaic 46, XY (46) and 45, X (4) |
| Noonan syndrome (n=2) | 1:1 | 7.2 (5.3–9.1) | Het. SOS2 gene mutation (c.1775G>T) (n=1) Het. A2ML1 gene mutation (c.1175G>T) (n=1) |
| Silver-Russell syndrome (n=1) | M | 14.9 | Clinical diagnosis with NHCSS score 4/6* |
| SGA with no catch-up growth (n=21) | 15:6 | 6.2 (1.3–15) | Birth weight SDS <−2.0 and height <−2.0 SDS at 4 years |
| SHOX (n=1) | M | 14.3 | Large deletion 47.5 kb 160 kb downstream of SHOX |
| Other genetic diagnosis (n=2) | 2:0 | 3.0 (2.8–3.2) | Leigh syndrome SURF1 gene mutation (p.Arg264fs) Myhre syndrome SMAD4 gain of function gene mutation |
| Secondary growth failure (n=23) | |||
| GH deficiency (n=17) | 14:3 | 8.0 (2.0–15.8) | GH peak of <6.7 ng/L |
| Coeliac disease (n=1) | F | 14.0 | Anti-TTG IgA >200, confirmed by duodenal biopsy |
| Hypothyroidism (n=1) | F | 19.9 | TSH 19.0miU/L, fT4 11.6 pmol/L (NR 0.27–4.2 and 10.5–24.5, respectively) |
| GH-IGF-I axis disorder (n=4) | 3:1 | 8.5 (2.2–16.5) | Het. GHR gene mutation 42718139T>G, c.810–15T>G) (n=1) Het. missense IGFI gene variant (n=1) Large deletion (0.24 mB) at chromosome 15q26.3 (haploinsufficiency IGF1R gene) (n=1) Primary IGF-I deficiency - diagnosed by IGFGT (n=1) |
*Triangular face, large head, minimal subcutaneous fat, poor feeding and slow weight gain.
GH deficiency, growth hormone deficiency diagnosed on GH provocation test (insulin tolerance or glucagon as per standard protocols) 36 with sex hormone priming for boys >10 years and testicular volumes of 9 years with Tanner breast stage ≤2; IGFGT, IGF-1 generation test (GH 0.033 mg/kg/day over 5 days according to standard ‘IGFGT’ established protocol) primary IGF-I deficiency defined as IGF-1 increment <15 ng/mL; NR, normal range; SDS, SD scores; SGA, small for gestational age (birth weight and/or length <−2 SDS) with no catch-up growth after 2–3 years; SHOX, short stature homeobox gene.