• Clinical science

Tall stature and abnormally rapid growth

Abstract

Tall stature is defined as a height of more than 2 standard deviations above the population mean or exceeding the 97th percentile for age and sex. In most cases, tall stature represents an acceptable normal variation in growth. However, tall stature can also be the result of an underlying pathology (i.e., endocrine or genetic abnormalities). Differentiating between normal or pathological growth variations involves a thorough medical history and clinical examination. Bone age tests, karyotyping, and endocrinological tests can confirm the diagnosis of a pathological cause.

Overview

  • Definition: A height of more than 2 standard deviations above the population mean or exceeding the 97th percentile on the normal growth curve for age and sex.
  • Most tall children do not have a pathological cause

Evaluation of growth

  1. History
    • Determine midparental height
    • Assess milestones (exclude developmental delay)
  2. Physical examination
    • Accurate serial measurements of individual body areas
      • Length or height
      • Growth velocity
      • Proportional vs disproportional growth
    • Exclude the following:
  3. Further diagnostic measures (if a pathological cause is suspected)

Differential diagnosis

Etiology Characteristic features
Nonpathological Familial/Constitutional tall stature
  • Family history
  • Projected height within 5 cm of midparental height
  • Advanced bone age
Endocrine Hyperthyroidism

Obesity

  • BMI
  • Slightly advanced bone age
  • Modest overgrowth
  • Early onset of puberty
  • Almost normal final height
Pituitary gigantism (growth hormone excess)
  • Coarse facial features, frontal bossing, prognathism
  • Tumor mass symptoms: headaches, visual impairment
  • ↑ serum IGF-1
  • GH after oral glucose test
Precocious puberty
  • : Breast development before 8 years
  • : Testicular enlargement before 9 years
  • Abnormal LH, FSH, estradiol, testosterone, 17 alpha-hydroxyprogesterone, BHCG levels
Genetic Beckwith-Wiedemann syndrome
Homocystinuria
  • Marfanoid habitus, inferior displacement of lens, developmental delay
  • Abnormal homocysteine and methionine
Klinefelter syndrome
Marfan syndrome
  • Marfanoid habitus, superior subluxation of lens, kyphoscoliosis, cardiac abnormalities
  • FBN1 gene mutation
Fragile X syndrome (Martin-Bell syndrome)
  • Large ears, high-arched palate, long face, pes planus, macroorchidism
  • FMR 1 gene mutation
Sotos syndrome (Cerebral gigantism)
Weaver syndrome
  • Micrognathia, broad forehead, camptodactyly
  • Advanced bone age
47,XYY syndrome and 47,XXX syndrome
  • 47,XYY syndrome
    • Developmental delay
    • Fertility problems
    • Acne
  • XXX syndrome
    • Tall stature
    • Delayed motor and language development
    • Learning disabilities
    • Menstrual abnormalities, occasionally fertility problems
Neurofibromatosis type 1
  • Cafe-au-lait spots or hyperpigmented macules, axillary or inguinal freckles, neurofibromas

References:[1][2][3][4][5]

Endocrine disorders

Gigantism

Other causes

References:[6][7]

Genetic disorders

Beckwith-Wiedemann syndrome

47,XYY syndrome and 47,XXX syndrome

  • Etiology: : excess growth syndrome, which is caused by an additional Y chromosome in males (XYY) and an additional X chromosome in females (XXX)
  • Epidemiology
  • Clinical features
    • XYY syndrome
      • Tall stature
      • Sometimes severe acne
      • Delayed language development
      • Learning disabilities
      • Behavioral problems
      • Fertility problems (decreased sperm count) possible
    • XXX syndrome
      • Tall stature
      • Delayed motor and language development
      • Learning disabilities
      • Menstrual abnormalities, occasionally fertility problems
  • Diagnosis
    • The majority of triple X women or double Y men are never diagnosed.
    • Chromosome analysis
  • Treatment
    • Only symptomatic treatment is possible
    • Speech therapy
    • Physical, occupational, and educational therapy
    • Reproductive specialist in case of fertility problems

Sotos syndrome (cerebral gigantism)

  • Epidemiology: ∼ 1/14,000 newborns
  • Etiology: excess growth syndrome, which manifests either congenitally or within the first 4 years of life. Sotos syndrome is caused by a mutation in the NSD1 gene on chromosome 5.
  • Symptoms
    • Tall stature
    • Macrocephalus
    • Facies
      • High forehead
      • Elongated face
      • Hypertelorism
      • Pointed chin
      • Receding hairline
    • Psychomotor retardation
    • Hypotonia
    • Delays in achieving milestones (e.g., walking, talking, clumsiness)
    • Diagnosis
      • Usually clinical
      • DNA studies (5q35 microdeletions and partial NSD1 deletions in ∼ 10–15% of cases.
      • Prenatal diagnosis possible
    • Treatment
      • Only symptomatic treatment is possible
      • Multiprofessional approach (pediatricians, neurologists, surgeons, speech pathologists, orthopedics, physical therapists and others).
    • Course
      • Normal growth rate from 3–5 years of age (only moderately increased adult height)
      • Permanent cognitive developmental impairments are common.

Other causes

References:[8][9][10][4][11][12][13]