Table 2

The range of diagnoses identified in children found to have pathological causes for their short stature (‘pathological short stature’ group 1) (n=51)

Age or mean age (range)Clinical details
Primary growth failure (n=28)
Turner syndrome (n=1)F13.9Mosaic 46, XY (46) and 45, X (4)
Noonan syndrome (n=2)1:17.2
Het. SOS2 gene mutation (c.1775G>T) (n=1)
Het. A2ML1 gene mutation (c.1175G>T) (n=1)
Silver-Russell syndrome (n=1)M14.9Clinical diagnosis with NHCSS score 4/6*
SGA with no catch-up growth (n=21)15:66.2
Birth weight SDS <−2.0 and height <−2.0 SDS at 4 years
SHOX (n=1)M14.3Large deletion 47.5 kb 160 kb downstream of SHOX
Other genetic diagnosis (n=2)2:03.0
Leigh syndrome SURF1 gene mutation (p.Arg264fs)
Myhre syndrome SMAD4 gain of function gene mutation
Secondary growth failure (n=23)
GH deficiency (n=17)14:38.0
GH peak of <6.7 ng/L
Coeliac disease (n=1)F14.0Anti-TTG IgA >200, confirmed by duodenal biopsy
Hypothyroidism (n=1)F19.9TSH 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)3:18.5
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.