Towards a Rational and Efficient Diagnostic Approach in Children Referred for Growth Failure to the General Paediatrician

Horm Res Paediatr. 2019;91(4):223-240. doi: 10.1159/000499915. Epub 2019 Jun 13.

Abstract

Based on a recent Dutch national guideline, we propose a structured stepwise diagnostic approach for children with growth failure (short stature and/or growth faltering), aiming at high sensitivity for pathologic causes at acceptable specificity. The first step is a detailed clinical assessment, aiming at obtaining relevant clinical clues from the medical history (including family history), physical examination (emphasising head circumference, body proportions and dysmorphic features) and assessment of the growth curve. The second step consists of screening: a radiograph of the hand and wrist (for bone age and assessment of anatomical abnormalities suggestive for a skeletal dysplasia) and laboratory tests aiming at detecting disorders that can present as isolated short stature (anaemia, growth hormone deficiency, hypothyroidism, coeliac disease, renal failure, metabolic bone diseases, renal tubular acidosis, inflammatory bowel disease, Turner syndrome [TS]). We advise molecular array analysis rather than conventional karyotyping for short girls because this detects not only TS but also copy number variants and uniparental isodisomy, increasing diagnostic yield at a lower cost. Third, in case of diagnostic clues for primary growth disorders, further specific testing for candidate genes or a hypothesis-free approach is indicated; suspicion of a secondary growth disorder warrants adequate further targeted testing.

Keywords: ACAN; Growth disorders; IHH; Microarray; NPR2; SHOX; Short stature; Turner syndrome.

Publication types

  • Practice Guideline

MeSH terms

  • Age Determination by Skeleton*
  • Child
  • Child, Preschool
  • DNA Copy Number Variations*
  • Failure to Thrive* / blood
  • Failure to Thrive* / diagnosis
  • Failure to Thrive* / genetics
  • Failure to Thrive* / pathology
  • Female
  • Human Growth Hormone* / blood
  • Human Growth Hormone* / deficiency
  • Humans
  • Karyotyping*
  • Male
  • Uniparental Disomy*

Substances

  • Human Growth Hormone