Tall stature: a difficult diagnosis?

Meazza et al. Italian Journal of Pediatrics (2017) 43:66 DOI 10.1186/s13052-017-0385-5 REVIEW Open Access Tall stature: a difficult diagnosis? Cristina Meazza1* , Chiara Gertosio2, Roberta Giacchero3, Sara Pagani1 and Mauro Bozzola1 Abstract Referral for an assessment of tall stature is less common than for short stature. Tall stature is defined as a height more than two standard deviations above the mean for age. The majority of subjects with tall stature show a familial tall stature or a constitutional advance of growth (CAG), which is a diagnosis of exclusion. After a careful physical evaluation, tall subjects may be divided into two groups: tall subjects with normal appearance and tall subjects with abnormal appearance. In the case of normal appearance, the paediatric endocrinologist will have to evaluate the growth rate. If it is normal for age and sex, the subject may be classified as having familial tall stature, CAG or obese subject, while if the growth rate is increased it is essential to evaluate pubertal status and thyroid status. Tall subjects with abnormal appearance and dysmorphisms can be classified into those with proportionate and disproportionate syndromes. A careful physical examination and an evaluation of growth pattern are required before starting further investigations. Physicians should always search for a pathological cause of tall stature, although the majority of children are healthy and they generally do not need treatment to cease growth progression. The most accepted and effective treatment for an excessive height prediction is inducing puberty early and leading to a complete fusion of the epiphyses and achievement of final height, using testosterone in males and oestrogens in females. Alternatively, the most common surgical procedure for reducing growth is bilateral percutaneous epiphysiodesis of the distal femur and proximal tibia and fibula. This review aims to provide up-to-date information and suggestions about the diagnosis and management of children with tall stature. Keywords: Tall stature, Syndromes, Growth velocity, Puberty, Height Background Human growth is a complex and dynamic physiological process tightly regulated by genetic, hormonal, nutritional and environmental factors. It is characterised by somatic changes in stature, body proportion, and body composition that involve cell hyperplasia (increase in cell number), cell hypertrophy (increase in cell size) and apoptosis (programmed cell death) [1]. Growth can be considered to occur in four separate but closely integrated phases, according to dominant influence from different factors. The first of these is the intrauterine phase, dependent upon maternal factors, nutrition and placental function, and coordinated by growth-promoting factors. The second is the infancy phase of growth, occurring mainly during the first 2–3 years of post-natal life; * Correspondence: 1 Department of Internal Medicine and Therapeutics, Unit of Pediatrics and Adolescentology, University of Pavia, Fondazione IRCCS Policlinico San Matteo, Piazzale C. Golgi 19, 27100 Pavia, Italy Full list of author information is available at the end of the article this period is driven by nutritional factors. The third phase of growth is the childhood phase, during which growth hormone (GH) and thyroid hormones become important in regulating growth. Finally, the pubertal growth spurt is controlled by the synergistic action of GH and sex steroids. [1]. An individual’s potential for growth is influenced by a number of genetic, environmental and hormonal factors. Children with tall stature are rarely referred to a paediatric endocrinologist for investigations about their condition, much less often than a referral for short stature. However, although most tall children are healthy but there are pathological causes of tall stature, paediatricians should always consider this eventuality [2]. In fact, some syndromes with severe complications are associated with abnormal body measurements including sitting height and arm span. However, a thorough history including information on birth, physical examination and evaluation of the growth chart may suffice to conclude whether there is a © The Author(s). 2017 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Meazza et al. Italian Journal of Pediatrics (2017) 43:66 Page 2 of 8 benign cause for tall stature. For example, increased birth weight and length are observed in Beckwith-Wiedemann syndrome, while developmental problems may be associated with Klinefelter, Triple X, fragile X, homocystinuria, Sotos and Weaver syndrome. Furthermore, an accurate medical history may reveal a syndromic cause: lens luxation may suggest homocystinuria or Marfan syndrome, cardiovascular problems are typical of Marfan syndrome, neonatal hypotonia is present in Sotos syndrome and abdominal wall and macroglossia defects can be seen in Beckwith-Wiedemann syndrome. A careful history and a precise physical examination are essential in order to point towards the cause of tall stature and to decide which diagnostic tests are necessary to reach a diagnosis. An X-ray of the non-dominant hand should be used to evaluate the skeletal maturity of tall children and it is useful to predict adult height. The available methods to predict adult height are, however, imperfect as BayleyPinneau method overestimate adult height and TannerWhitehouse Mark 1 and 2 overestimate or underestimate it depending on bone age [3, 4]. Finally, in our opinion, it is important to follow-up tall subjects since some epidemiological studies have shown that taller people are at increased risk of common cancer such as breast, ovary, prostate and large bowel [5, 6]. In particular, a British study showed that tall women have a greater risk of developing breast, endometrium, colon and ovarian cancer [7] and another Swedish study found that total cancer risk and risks of breast cancer and melanoma were higher with increasing height [8]. Management of a child with tall stature Firstly, tall stature is defined as a height more than two standard deviations (SD) above the mean for age, i.e. greater than the 97th percentile for sex and age. It is important to take into account the ethnic background of the patient and use the appropriate growth charts when measuring a child. Secondly, a child can also be considered tall in relation to his/her midparental height (MPH), when his/her height is more than two SD (...truncated)