Constitutional growth delay

Constitutional delay of growth and puberty (CDGP) is a term describing a temporary delay in the skeletal growth and thus height of a child with no physical abnormalities causing the delay. Short stature may be the result of a growth pattern inherited from a parent (familial) or occur for no apparent reason (idiopathic). Typically at some point during childhood, growth slows down, eventually resuming at a normal rate. CDGP is the most common cause of short stature and delayed puberty.

Background

Children with constitutional delay of growth and puberty (CDGP), the most common cause of short stature and pubertal delay in males, typically have slowed linear growth within the first 3 years of life. In this variant of normal growth, linear growth velocity and weight gain slows beginning as young as age 3–6 months, resulting in downward crossing of growth percentiles, which often continues until age 2–3 years. At that time, growth resumes at a normal rate, and these children grow either along the lower growth percentiles or beneath the curve but parallel to it for the remainder of the prepubertal years.

At the expected time of puberty, the height of children with CDGP begins to drift further from the growth curve because of delay in the onset of the pubertal growth spurt. Catch-up growth, onset of puberty, and pubertal growth spurt occur later than average, resulting in normal adult stature and sexual development. Although CDGP is a variant of normal growth rather than a disorder, delays in growth and sexual development may contribute to psychological difficulties, warranting treatment for some individuals. Recent studies have suggested that referral bias is largely responsible for the impression that normal short stature per se is a cause of psychosocial problems; nonreferred children with short stature do not differ from those with more normal stature in school performance or socialization.

Pathophysiology

CDGP is a global delay in development that affects every organ system. Delays in growth and sexual development are quantified by skeletal age, which is determined from bone age radiographic studies of the left hand and wrist. Growth and development are appropriate for an individual's biologic age (skeletal age) rather than for their chronologic age. Timing and tempo of growth and development are delayed in accordance with the biologic state of maturity.

Approximately 15% of patients with short stature referred for endocrinologic evaluation have CDGP. Individuals with CDGP and familial short stature represent another 23%. The frequency of CDGP may be underestimated because individuals with milder delays and those who are not psychologically stressed may not be seen by subspecialists. In a study of 555 (out of 80,000) schoolchildren below the third percentile in height for age with growth rates below normal (<5 cm/y), twice as many boys as girls were affected. CDGP was found in 28% of boys and 24% of girls, and another 18% of boys and 16% of girls had familial short stature in combination with CDGP.

Mortality/Morbidity

CDGP is not associated with increased mortality because it is a variant of normal growth rather than a disease. However, in some affected individuals, it can be associated with significant psychological stress, resulting in poor self-image and social withdrawal. In recent years, researchers have also found that individuals with CDGP may be at increased risk for reduced bone mass in adulthood because of the delay in sex steroid influence on bone accrual during adolescence.

Frequency

Although the epidemiologic data indicate that all variants of normal growth are twice as common in boys as in girls, referrals for short stature reflect an even more divergent sex ratio. This likely reflects greater concern about males who are shorter than their peers or who have delayed sexual development. No racial bias has been identified. Patterns of growth consistent with CDGP occur in infants as young as 3–6 months. However, individuals often do not seek medical attention until puberty, when lack of sexual development becomes a concern and discrepancy in height from peers is magnified by the delay in pubertal growth spurt.

Clinical History

Individuals with constitutional delay of growth and puberty (CDGP) are usually of normal size at birth. Deceleration in both height and weight velocity typically occurs within the first 3–6 months of life. This shift downward is similar to that observed in infants experiencing normal lag-down growth but tends to be more severe and prolonged. Individual variation is substantial; however, most children resume a normal growth velocity by age 2–3 years. During childhood, these individuals grow along or parallel to the lower percentiles of the growth curve.

Skeletal age, which is estimated from radiographic studies of the left hand and wrist, is usually delayed (typically 2-4 y by late childhood) and is most consistent with the child's height age (age for which a child's height is at the 50th percentile) rather than the child’s chronologic age. Because the timing of the onset of puberty, pubertal growth spurt, and epiphyseal fusion are determined by a child's skeletal age (biologic age), children with CDGP are often referred to as "late bloomers."

At the usual age for puberty, these children continue to grow at a prepubertal rate appropriate for their biologic stage of development. Natural slowing of linear growth just before onset of puberty may be exaggerated, emphasizing the difference in size from peers who are accelerating in growth. The timing of the pubertal growth spurt is delayed, and the spurt may be prolonged with a lower peak height velocity. In patients with both CDGP and familial short stature, the degree of growth retardation may appear more severe, but the adult height is appropriate for the genetic background.

Physical

Physical examination findings in patients with CDGP are essentially normal, with the exception of immature appearance for age. Body proportions may reflect the delay in growth. During childhood, the upper-to-lower body ratio may be greater than normal, reflecting more infantile proportions. In adults, the ratio is often reduced (i.e., <1 in whites, <0.9 in blacks) as a result of the longer period of leg (long bone) growth.

Causes

CDGP is thought to be inherited from multiple genes from both parents. The strong role of heredity is reflected in the 60-90% likelihood of this growth pattern in a family member of the same or opposite sex. A delay in the reactivation of the hypothalamic-pituitary pulse generator results in a later onset of puberty.

Synonyms

See also

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