Constitutional Delay of Growth and Puberty
Constitutional delay of growth and puberty (CDGP) is a benign variant of normal development characterized by deceleration of linear growth in the first 3 years of life, followed by normal growth velocity during childhood, delayed bone age, delayed puberty, and eventual attainment of normal adult height within genetic potential. 1
Key Defining Features
Growth Pattern:
- Initial deceleration of length/height occurs in the first 3 years of life 1
- Normal or near-normal height velocity is maintained during childhood after this initial deceleration 1, 2
- Growth velocity remains the single most useful indicator for assessment, ideally measured over 4-6 month intervals 1
Bone Age and Pubertal Development:
- Bone age is characteristically delayed compared to chronological age, which distinguishes CDGP from familial short stature where bone age matches chronological age 1, 2, 3
- The delayed bone age indicates increased remaining growth potential, allowing for catch-up growth during an extended growth period 1
- Pubertal development is delayed but eventually complete: boys have testicular volume <4 mL at age 14 years, and girls have breast stage <B2 at age 13.5 years 2
Family History:
- A familial pattern of delayed growth and development is frequently observed, with 50-75% of patients having 2 or more affected family members 2, 4
- Inheritance often follows an autosomal dominant pattern with variable penetrance 4
Clinical Presentation
Demographics:
- Male predominance is striking, with boys affected approximately 4-5 times more frequently than girls 5, 4
- Short stature (height-for-age less than 2 standard deviations below average, or below the 3rd percentile) is present in approximately 91% of cases 1, 4
Distinguishing from Pathologic Conditions:
- Unlike permanent hypogonadotropic hypogonadism, CDGP shows spontaneous pubertal progression before age 18 years 2, 6
- Unlike familial short stature, bone age is delayed rather than matching chronological age 2, 3
- Growth velocity remains normal during childhood, ruling out growth hormone deficiency or other pathologic causes 1, 3
Adult Height Outcomes
Expected Final Height:
- Final adult height typically falls within the normal range, though it may not fully reach mid-parental target height 1, 2
- Males may achieve mean adult height of approximately 169.5 cm (1.2 SD below the 50th percentile), falling about 5.1 cm below target height based on mid-parental height 7
- Females may achieve mean adult height of approximately 156 cm (1.3 SD below the 50th percentile), falling about 5.3 cm below target height 7
- Some degree of disproportionately short trunk may persist 8
Genetic Basis
Recent genetic studies have identified rare heterozygous variants in approximately 25% of CDGP patients, most commonly in genes involved in GnRH migration and metabolism, including IGSF10, GHSR, CHD7, SPRY4, WDR11, SEMA3A, and IL17RD 4. This suggests genetic heterogeneity underlying this common pediatric condition 4.
Clinical Significance
Psychosocial Impact:
- Despite being a variant of normal rather than a disease, short stature and delayed sexual development can cause significant psychological distress and poor academic performance 6
- Treatment may be indicated when adolescents experience psychological difficulties related to their delayed development 6
Common Pitfall:
- CDGP is a diagnosis of exclusion; other causes of delayed puberty must be systematically ruled out, including permanent hypogonadotropic hypogonadism, functional hypogonadotropic hypogonadism (from chronic diseases like celiac disease, inflammatory bowel disease, renal insufficiency, or anorexia nervosa), and primary gonadal failure 6, 9