Growth and Development Assessment

Introduction to Growth Abnormalities

• Crossing of several centile lines between 3 years and adolescence suggests pathology, according to the American College of Medical Genetics and Genomics 1
• Nearly 50% of children referred for short stature evaluation have non-pathologic causes, as reported by the American College of Medical Genetics and Genomics 1

Definition and Diagnosis of Short Stature

• Short stature is defined as height-for-age less than 2 standard deviations below the mean (below 3rd percentile) 1, 1
• Disproportionate short stature suggests skeletal dysplasia, while proportionate short stature with advanced bone age may indicate endocrine disorders or genetic conditions, as recommended by the Genetics Society 1

Pathologic Causes of Short Stature

• Chromosomal abnormalities, primarily Turner syndrome and variants, account for 19% of pathologic causes of short stature, as stated by the American College of Medical Genetics and Genomics 1
• Multiple malformation syndromes account for 3% of pathologic causes of short stature, according to the American College of Medical Genetics and Genomics 1
• Certain endocrinopathies with excess sex hormone production can cause accelerated bone maturation, leading to early growth cessation and compromised adult height, as indicated by the Endocrine Society 1
• Conditions such as heterozygous ACAN gene mutations and precocious puberty can also lead to accelerated bone maturation, resulting in significant implications for growth potential, as suggested by the Endocrine Society 1

Growth Hormone Therapy

• Growth hormone (GH) therapy is contraindicated in patients with accelerated bone maturation, as it will not improve final height and may accelerate epiphyseal fusion, according to the American Academy of Pediatrics, the Endocrine Society, and the American College of Medical Genetics and Genomics 2, 2, 2
• GH therapy may be considered for children with genetic syndromes, including SHOX gene-related disorders and cardio-facio-cutaneous syndrome with documented GH deficiency, as recommended by the American Academy of Pediatrics 3
• Contraindications for GH therapy include active malignancy, uncontrolled diabetes mellitus, pre-existing papilledema, and known hypersensitivity to growth hormone, as stated by the FDA and the American Academy of Pediatrics 2

Monitoring and Evaluation

• Regular bone age assessment every 6-12 months to track progression, and height velocity monitoring, as recommended by the American Academy of Pediatrics 2
• Monitoring bone age every 6 months is recommended for children receiving GH therapy, with annual bone age assessment and IGF-1 monitoring for safety and dosage adjustment 2
• Assessing growth velocity and pattern is crucial, as growth velocity below the 25th percentile with height below the 3rd percentile suggests pathologic growth failure, according to the American Academy of Pediatrics 2
• Evaluating for disproportionate vs. proportionate short stature is necessary, as it helps in identifying the underlying cause of short stature, as recommended by the Genetics Society 1

Special Considerations

• Chronic kidney disease (CKD) stages 3-5 or dialysis may require GH therapy when height is below the 3rd percentile and height velocity is below the 25th percentile, as recommended by the American Academy of Pediatrics and the National Kidney Foundation 2
• The mean first-year growth rate for CKD patients on GH therapy is 10.8 cm/yr, compared to 6.5 cm/yr in controls, according to the National Kidney Foundation 2
• For specific conditions like precocious puberty, GnRH agonists may help slow bone maturation and improve height outcomes, as suggested by the Endocrine Society 2, 1

Genetic Testing

• SHOX gene testing is recommended for children with subtle skeletal changes or significant short stature (>3 SD) without other diagnosis, with chromosomal analysis recommended for girls with short stature to rule out Turner syndrome, as noted by the American College of Medical Genetics and Genomics 1

• Early identification of SHOX-related phenotypes is crucial for correct diagnosis and management, with the American Academy of Pediatrics recommending evaluation for SHOX gene mutations in children with short stature and a family history of short stature or skeletal abnormalities consistent with Léri-Weill dyschondrosteosis 1