Tall Stature: A Challenge for Clinicians

Author(s): Beatriz Corredor, Mehul Dattani, Chiara Gertosio, Mauro Bozzola*.

Journal Name: Current Pediatric Reviews

Volume 15 , Issue 1 , 2019

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Graphical Abstract:


Abstract:

Clinicians generally use the term “tall stature” to define a height more than two standard deviations above the mean for age and sex. In most cases, these subjects present with familial tall stature or a constitutional advance of growth which is diagnosed by excluding the other conditions associated with overgrowth. Nevertheless, it is necessary to be able to identify situations in which tall stature or an accelerated growth rate indicate an underlying disorder. A careful physical evaluation allows the classification of tall patients into two groups: those with a normal appearance and those with an abnormal appearance including disproportion or dysmorphism. In the first case, the growth rate has to be evaluated and, if it is normal for age and sex, the subjects may be considered as having familial tall stature or constitutional advance of growth or they may be obese, while if the growth rate is increased, pubertal status and thyroid function should be evaluated. In turn, tall subjects having an abnormal appearance can be divided into proportionate and disproportionate syndromic patients. Before initiating further investigations, the clinician needs to perform both a careful physical examination and growth evaluation. To exclude pathological conditions, the cause of tall stature needs to be considered, although most children are healthy and generally do not require treatment to inhibit growth progression.

In particular cases, familial tall stature subject can be treated by inducing puberty early and leading to a complete fusion of the epiphyses, so final height is reached. This review aims to provide proposals about the management of tall children.

Keywords: Tall stature, proportionate syndromes, disproportionate syndromes, challenge, clinicians, puberty.

[1]
Backeljauw P, Dattani M, Cohen P, Rosenfeld R. Disorders of Growth Hormone/Insulin-Like Growth Factor. In: Sperling MA, Eds Pediatric endocrinology 4th Ed . Eselvier Philadelphia 2014; pp. 299-405.
[2]
Wei C, Gregory JW. Physiology of normal growth. Paediatr Child Health 2009; 19: 236-40.
[3]
Davies JH, Cheetham T. Investigation and management of tall stature. Arch Dis Child 2014; 99: 772-7.
[4]
Meazza C, Gertosio C, Giacchero R, Pagani S, Bozzola M. Tall stature: A difficult diagnosis? Ital J Pediatr 2017; 43: 66-74.
[5]
Kamien B, Ronan A, Poke G, et al. A clinical review of generalized overgrowth syndromes in the era of massively parallel sequencing. Mol Syndromol 2018; 9(2): 70-82.
[6]
Coutant R, Donzeau A, Decrequy A, Louvigné M, Bouhours-Nouet N. How to investigate a child with excessive growth? Ann Endocrinol 2017; 78(2): 98-103.
[7]
Albuquerque E, Scalco R, Jorge A. Management of endocrine disease: Diagnostic and therapeutic approach of tall stature. Eur J Endocrinol 2017; 176(6): 339-53.
[8]
Dickerman Z, Loewinger J, Laron Z. The pattern of growth in children with constitutional tall stature from birth to age 9 years. A longitudinal study. Acta Paediatr Scand 1984; 73: 530-6.
[9]
Barstow C, Rerucha C. Evaluation of short and tall stature in children. Am Fam Phys 2015; 92: 43-50.
[10]
Papadimitriou A, Nicolaidou P, Fretzayas A, Chrousos GP. Clinical review: Constitutional advancement of growth, a.k.a. early growth acceleration, predicts early puberty and childhood obesity. J Clin Endocrinol Metab 2010; 95: 4535-41.
[11]
Garrone S, Radetti G, Sidoti M, et al. Increased Insulin-like Growth factor (IGF)-II and IGF/IGF-binding protein ratio in prepubertal constitutionally tall children. J Clin Endocrinol Metab 2002; 87: 5455-60.
[12]
Júlíusson PB, Brannsether B, Kristiansen H, et al. Should children with overweight or obesity be excluded from height references? Arch Dis Child 2015; 100: 1044-8.
[13]
Marino R, Perez Garrido N, Costanzo M, et al. Five new cases of 46, XX aromatase deficiency: Clinical follow-up from birth to puberty, a novel mutation, and a founder effect. J Clin Endocrinol Metab 2015; 100: E301-7.
[14]
Smith EP, Boyd J, Frank GR, et al. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med 1994; 331: 1056-61.
[15]
Quaynor SD, Stradtman EW Jr, Kim HG, et al. Delayed puberty and estrogen resistance in a woman with estrogen receptor alpha variant. N Engl J Med 2013; 369: 164-71.
[16]
Neely E, Crossen S. Precocious puberty. Curr Opin Obstet Gynecol 2014; 26(5): 332-8.
[17]
El-Maouche D, Arlt W, Merke D. Congenital adrenal hyperplasia. The Lancet 2017; 390(10108): 2194-210.
[18]
Marques P, Korbonits M. Genetic aspects of pituitary adenomas. Endocrinol Metab Clin N Am 2017; 46: 335-74.
[19]
Pratt V, McLeod H, Dean L, Malheiro A, Rubinstein W, Eds. Medical Genetics Summaries [Internet]. Bethesda, MD: National Center for Biotechnology Information (US) 2012.
[20]
Boyce AM, Collins MT, Pagon RA, et al. editors GeneReviews® [Internet] . 1993-2017.
[21]
Edmondson A, Kalish J. Overgrowth syndromes. J Pediatr Genet 2015; 4(3): 136-43.
[22]
Tatton-Brown K, Douglas J, Coleman K, et al. Genotype-phenotype associations in sotos syndrome: An Analysis of 266 Individuals with NSD1 Aberrations. AJHG 2005; 77(2): 193-204.
[23]
Villani A, Greer M, Kalish J, Nakagawara A, et al. Recommendations for cancer surveillance in individuals with rasopathies and other rare genetic conditions with increased cancer risk. Clin Cancer Res 2017; 23(12): e83-90.
[24]
(a)Klaassens M, Morrogh D, Rosser EJ, et al. Malan syndrome: Sotos-like overgrowth with de novo NFIX sequence variants and deletions in six new patients and a review of the literature. Eur J Human Genet 2014; 23(5); (b)Kant S, Wit J, Breuning M. Genetic Analysis of Tall Stature. Horm Res Paediatr 2005; 64(3): 149-56.
[25]
Priolo M, Schanze D, Tatton-Brown K, et al. Further delineation of Malan syndrome. Hum Mutat 2018; 39(9): 1226-37.
[26]
Tatton-Brown K, Murray A, Hanks S, Douglas J, et al. Childhood Overgrowth Consortium Rahman N. Weaver syndrome and EZH2 mutations: Clarifying the clinical phenotype. Am J Med Genet A 2013; 161A: 2972-80.
[27]
Cohen A, Gibson W. EED-associated overgrowth in a second male patient. J Hum Genet 2016; 61(9): 831-4.
[28]
Imagawa E, Albuquerque E, Isidor B, et al. Novel SUZ12 mutations in Weaver-like syndrome. Clin Genet 2018; 94(5): 461-6.
[29]
Brown K, Zachariou A, Loveday C, et al. The Tatton-Brown-Rahman Syndrome: A clinical study of 55 individuals with de novo constitutive DNMT3A variants. Wellcome Open Res 2018; 3: 46.
[30]
Rajan-Babu IS, Chong SS. Molecular correlates and recent advancements in the diagnosis and screening of FMR1-related disorders. Genes (Basel) 2016; 7: E87.
[31]
Terracciano A, Chiurazzi P, Neri G. Fragile X syndrome. Am J Med Genet C Semin Med Genet 2005; 137C: 32-7.
[32]
Bernier R, Golzio C, Xiong B, et al. Disruptive chd8 mutations define a subtype of autism early in development. Cell 2014; 158(2): 263-76.
[33]
Garganta CL, Bodurtha JN. Report of another family with Simpson-Golabi-Behmel syndrome and a review of the literature. Am J Med Genet 1992; 44: 129-35.
[34]
DeBaun MR, Ess J, Saunders S. Simpson Golabi Behmel syndrome: Progress toward understanding the molecular basis for overgrowth, malformation, and cancer predisposition. Mol Gen Metab 2001; 72: 279-86.
[35]
Verstraeten A, Alaerts M, Van Laer L, Loeys B. Marfan syndrome and related disorders: 25 years of gene discovery. Hum Mutat 2016; 37: 524-31.
[36]
De Maio F, Fichera A, De Luna V, Mancini F, Caterini R. Orthopaedic aspects of Marfan syndrome: The experience of a referral center for diagnosis of rare diseases. Adv Orthop 2016; 2016: 8275391.
[37]
Silao CL, Fabella TD, Rama KI, Estrada SC. Novel cystathionine β-synthase gene mutations in a Filipino patient with classic homocystinuria. Pediatr Int 2015; 57: 884-7.
[38]
Soejima H, Higashimoto K. Epigenetic and genetic alterations of the imprinting disorder Beckwith-Wiedemann syndrome and related disorders. J Hum Genet 2013; 58(7): 402-9.
[39]
Tartaglia NR, Howell S, Sutherland A, Wilson R, Wilson L. A review of trisomy X (47,XXX). Orphanet J Rare Dis 2010; 5: 8.
[40]
Wigby K, D’Epagnier C, Howell S, et al. Expanding the phenotype of Triple X syndrome: A comparison of prenatal versus postnatal diagnosis. Am J Med GenetPart A 2016; 170(11): 2870-81.
[41]
Kant S, Wit J, Breuning M. Genetic analysis of tall stature. Horm Res Paediatr 2005; 64(3): 149-56.
[42]
Perola M, Sammalisto S, Hiekkalinna T, et al. Combined genome scans for body stature in 6,602 European twins: Evidence for common Caucasian loci. PLoS Genet 2007; 3: e97.
[43]
Silventoinen lventoinen K, Sammalisto S, Perola M, et al. Heritability of adult body height: A comparative study of twin cohorts in eight countries. Twin Res 2003; 6: 399-408.
[44]
Hendriks AE, Brown MR, Boot AM, Oostra BA, Drop SL, Parks JS. Genetic variation in candidate genes like the HMGA2 gene in the extremely tall. Horm Res Paediatr 2011; 76: 307-13.
[45]
Bocciardi R, Giorda R, Buttgereit J, et al. Overexpression of the C-type Natriuretic Peptide (CNP) is associated with overgrowth and bone anomalies in an individual with balanced t(2;7) translocation. Hum Mutat 2007; 28: 724-31.
[46]
Moncla A, Missirian C, Cacciagli P, et al. A cluster of translocation breakpoints in 2q37 is associated with overexpression of NPPC in patients with a similar overgrowth phenotype. Hum Mutat 2007; 28: 1183-8.
[47]
Miura K, Namba N, Fujiwara M, et al. An overgrowth disorder associated with excessive production of cGMP due to a gain-of-function mutation of the natriuretic peptide receptor 2 gene. PLoS One 2012; 7: e42180.
[48]
Miura K, Kim OH, Lee HR, et al. Overgrowth syndrome associated with a gain-of-function mutation of the natriuretic peptide receptor 2 (NPR2) gene. Am J Med Genet A 2014; 164A: 156-63.
[49]
Hannema SE, van Duyvenvoorde HA, Premsler T, et al. An activating mutation in the kinase homology domain of the natriuretic peptide receptor-2 causes extremely tall stature without skeletal deformities. J Clin Endocrinol Metab 2013; 98: E1988-98.
[50]
Toydemir RM, Brassington AE, Bayrak-Toydemir P, et al. A novel mutation in FGFR3 causes camptodactyly, tall stature, and hearing loss (CATSHL) syndrome. Am J Hum Genet 2006; 79: 935-41.
[51]
Makrythanasis P, Temtamy S, Aglan MS, Otaify GA, Hamamy H, Antonarakis SE. A novel homozygous mutation in FGFR3 causes tall stature, severe lateral tibial deviation, scoliosis, hearing impairment, camptodactyly, and arachnodactyly. Hum Mutat 2014; 35: 959-63.
[52]
Gupta S, Fahiminiya S, Wang T, et al. Somatic overgrowth associated with homozygous mutations in both MAN1B1 and SEC23A. Cold Spring Harb Mol Case Stud 2016; 2: a000737.
[53]
Pagani S, Radetti G, Meazza C, Bozzola M. Analysis of growth hormone receptor gene expression in tall and short stature children. J Pediatr Endocrinol Metab 2017; 30: 427-30.
[54]
Lin Y, van Duyvenvoorde H, Liu H, et al. Characterization of an activating R1353H insulin-like growth factor 1 receptor variant in a male with extreme tall height. Eur J Endocrinol 2018; 179(2): 85-95.
[55]
Gunnell D, Okasha M, Smith GD, Oliver SE, Sandhu J, Holly JM. Height, leg length, and cancer risk: A systematic review. Epidemiol Rev 2001; 23: 313-42.
[56]
Schouten LJ, Rivera C, Hunter DJ, et al. Height, body mass index, and ovarian cancer: A pooled analysis of 12 cohort studies. Cancer Epidemiol Biomarkers Prev 2008; 17: 902-12.
[57]
Green J, Cairns BJ, Casabonne D, Wright FL, Reeves G, Beral V. Height and cancer incidence in the Million Women Study: Prospective cohort, and meta-analysis of prospective studies of height and total cancer risk. Lancet Oncol 2011; 12: 785-94.
[58]
Benyl E, Linder M, Adami J, Palme M, Savendahl L. Positive association between height and cancer in the Swedish population. ESPE Abstracts (2015). 84 FC4.6
[59]
Joss EE, Temperli R, Mullis PE. Adult height in constitutionally tall stature: Accuracy of five different height prediction methods. Arch Dis Child 1992; 67: 1357-62.
[60]
de Waal WJ, Greyn-Fokker MH, Stijnen T, et al. Accuracy of final height prediction and effect of growth-reductive therapy in 362 constitutionally tall children. J Clin Endocrinol Metab 1996; 81: 1206-16.
[61]
Matthews D, Bath L, Högler W, Mason A, Smyth A, Skae M. Hormone supplementation for pubertal induction in girls. Arch Dis Child 2017; 102(10): 975-80.
[62]
Boehm U, Bouloux P, Dattani M, et al. European consensus statement on congenital hypogonadotropic hypogonadism-pathogenesis, diagnosis and treatment. Nat Rev Endocrinol 2015; 11(9): 547-64.
[63]
Howard S and, Dunkel L. Sex Steroid and Gonadotropin Treatment in Male Delayed Puberty. Puberty from Bench to Clinic Lessons for Clinical Management of Pubertal Disorders. Endocr Dev Basel Karger 2016; 29: 185-97.
[64]
Reinehr T, Gueldensupp M, Wunsch R, Bramswig JH. Treatment of tall stature in boys: Comparison of two different treatment regimens. Horm Res Paediatr 2011; 76: 343-7.
[65]
Upners EN, Juul A. Evaluation and phenotypic characteristics of 293 Danish girls with tall stature: Effects of oral administration of natural 17β-estradiol. Pediatr Res 2016; 80: 693-701.
[66]
de Waal W, Torn M, de Muinck Keizer-Schrama S, Aarsen R, Drop S. Long term sequelae of sex steroid treatment in the management of constitutionally tall stature. Arch Dis in Childhood 1995; 73(4): 311-5.
[67]
Hendriks AE, Boellaard WP, van Casteren NJ, et al. Fatherhood in tall men treated with high-dose sex steroids during adolescence. J Clin Endocrinol Metab 2010; 95: 5233-40.
[68]
Brook CG, Stanhope R, Preece MA, et al. Oestrogen treatment of tall stature. Arch Dis Child 1998; 79: 199.
[69]
Hindmarsh PC, Pringle PJ, Di Silvio L, Brook CG. A preliminary report on the role of somatostatin analogue (SMS 201-995) in the management of children with tall stature. Clin Endocrinol(Oxf) 1990; 32: 83-91.
[70]
Hindmarsh PC, Pringle PJ, Stanhope R, Brook CGD. The effect of a continuous infusion of a somatostatin analogue (octreotide) for two years on growth hormone secretion and height prediction in tall children. Clin Endocrinol 1995; 42: 509-15.
[71]
Noordam C, van Daalen S, Otten BJ. Treatment of tall stature in boys with somatostatin analogue 201-995: Effect on final height. Eur J Endocrinol 2006; 154: 253-7.
[72]
Hindmarsh PC. Long-term follow-up after bilateral percutaneous epiphysiodesis around the knee to reduce excessive predicted final height. Arch dis in childhood 2018; 103(3): 219-23.
[73]
Stalman SE, Pons A, Wit JM, Kamp GA, Plotz FB. Diagnostic work-up and follow-up in children with tall stature: A simplified algorithm for clinical practice. J Clin Res Pediatr Endocrinol 2015; 7: 260-7.
[74]
Hannema ES, Savendahl L. The evaluation and management of tall stature. Horm Res Paediatr 2016; 85: 347-52.
[75]
Benyi E, Berner M, Bjernekull I, et al. Efficacy and safety of percutaneous epiphysiodesis operation around the knee to reduce adult height in extremely tall adolescent girls and boys. Int J Pediatr Endocrinol 2010; 2010: 1-7.
[76]
Goedegebuure WJ, Jonkers F, Boot AM, et al. Long-term follow-up after bilateral percutaneous epiphysiodesis around the knee to reduce excessive predicted final height. Arch Dis Child 2018; 103: 219-23.


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Article Details

VOLUME: 15
ISSUE: 1
Year: 2019
Page: [10 - 21]
Pages: 12
DOI: 10.2174/1573396314666181105092917

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