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Annales d’Endocrinologie xxx (2017) xxx–xxx

Klotz Communications 2017: From the shortest to the tallest

How to investigate a child with excessive growth?

Que faire devant un enfant trop grand ?
Régis Coutant ∗, Aurélie Donzeau , Anne Decrequy , Mathilde Louvigné , Natacha Bouhours-Nouet
Paediatric Endocrinology Service, CHU d’Angers, 4, rue Larrey, 49000 Angers, France

Abstract
The diagnostic approach to tall stature in children is based on collecting birth data (macrosomia), sizes and family puberty, a family history of
constitutional or pathological tall stature, search for a delay of development, dysmorphia, disproportion, analysis of the growth velocity (normal or
accelerated), general examination and assessment of puberty, and bone age. When there is a history of psychomotor retardation, a family history of
pathological tall stature, or a disproportion in the clinical examination, the genetic causes of tall stature will be mentioned. The most frequent causes
are Marfan syndrome and similar, Sotos syndrome, Beckwith-Wiedemann syndrome, Klinefelter syndrome, and MEN2B. There are many genetic
syndromes with tall stature, justifying consultation with the geneticist. When the speed of growth is accelerated, first of all it evokes puberty and
early pseudopuberty, obesity and acromegaly. Finally, when the growth velocity is regular, and the parents are of tall stature, it evokes constitutional
tall stature: this is the most frequent diagnosis, to retain after having rejected pathological tall statures.
© 2017 Elsevier Masson SAS. All rights reserved.

Keywords: Tall stature; Growth velocity; Marfan syndrome; Sotos syndrome; MEN2B

Résumé
La démarche diagnostique devant une grande taille chez l’enfant s’appuie sur le recueil des coordonnées de naissance (macrosomie ?), des tailles
et pubertés familiales, des antécédents familiaux de grande taille constitutionnelle ou pathologique, la recherche d’un retard de développement,
d’une dysmorphie, d’une disproportion, sur l’analyse de la vitesse de croissance (normale ou accélérée), sur l’examen général et pubertaire, et
sur la réalisation d’un âge osseux. Lorsqu’il existe des ACTD de retard psychomoteur, une histoire familiale de grande taille pathologique, ou
une disproportion à l’examen clinique, les causes génétiques de grande taille seront évoquées. Les causes les plus fréquentes sont le syndrome de
Marfan et apparentés, le syndrome de Sotos, le syndrome de Wiedemann-Beckwith, le syndrome de Klinfelter, la MEN2B. Il existe de nombreux
syndromes génétiques avec grande taille, justifiant d’une consultation avec le généticien clinicien. Lorsque la vitesse de croissance est accélérée,
on évoque en premier lieu les pubertés et pseudopubertés précoces, l’obésité, l’acromégalie. Enfin, lorsque la vitesse de croissance est régulière,
et les parents de grande taille, on évoque la grande taille constitutionnelle : il s’agit du diagnostic le plus fréquent, à retenir après avoir éliminé les
grandes tailles pathologiques.
© 2017 Elsevier Masson SAS. Tous droits réservés.

Mots clés : Grande taille ; Vitesse de croissance ; Syndrome de Marfan ; Syndrome de Sotos ; MEN2B

1. Definitions and initial management
1.1. Definitions
Tall stature is defined as a size ranging beyond the threshold of
+2 standard deviations of the average population size for the age
∗ of more than 0.5 to 1 standard deviation) also merit medical
Corresponding author.
E-mail address: recoutant@chu-angers.fr (R. Coutant).
and gender. In France, a size greater than +2 standard deviations
at adult age corresponds to more than 187 cm for a man and more
than 175 cm for a woman. In the Netherlands, the same statistical
thresholds lead to a size greater than 194.5 cm and 180 cm, and
in Korea to 180 cm and 166.5 cm respectively (Fig. 1) [1].
A height beyond +2 standard deviations from the genetic tar-
get height (the average of the parental heights SD score) (Fig. 1),
or an acceleration of growth (arbitrarily a statural height gain
assessment (Fig. 2).

http://dx.doi.org/10.1016/j.ando.2017.04.006
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Please cite this article in press as: Coutant R, et al. How to investigate a child with excessive growth? Ann Endocrinol (Paris) (2017),
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Fig. 1. Size > +2 SD of the average population for age and sex, and > +2 SD the target genetic size.

Although the definition of tall stature is statistical (and there-
fore affects almost 2.5% of the population), it is a much less
frequent reason for consultation in Paediatrics that being small
(10 to 20 times less frequent), because tall stature is often
perceived as beneficial.
The request is often the result of a bad psychological toler-
ance towards tall stature, more often observed among girls [1–3]:
manifestations of anxiety and depression are more frequent
among girls of tall stature and could persist in adulthood [4].
However, women of tall stature have also reported the perception
of increased professional authority, accompanied by difficulties
with male subordinates, but no social or family disadvantages.
1.2. Initial management
The consultation will establish the height-weight growth
curve, body mass index, and cranial perimeter of the child,
collect the term and birth data (weight, length, and head circum-
ference), the height of the parents and first degree relatives (and
second degree), pubertal timing of the parents (age of menarche

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Fig. 2. “Abnormal” growth rate.

of the mother and approximate age of the pubertal growth spurt
of the father), personal and family history (neonatal hypogly-
caemia, cardiovascular pathology, ophthalmologic, neoplasia),
and delay of psychomotor development.
The clinical examination aims to find a heart murmur, anoma-
lies of the skin (stretch marks), skeletal (scoliosis, pectus
excavatum, hyperlaxity), facial dysmorphism and will evalu-
ate the pubertal stage. Standing height, sitting height, arm span,
and head circumference will be measured, all these elements are
important to the diagnostic orientation.
The determination of bone age is usual (in France, the most
often used reference is the atlas of radiographs of the left hand
and wrist by Greulich and Pyle). It can help to guide the diag-
nosis: strong advances of bone age being more often associated
with pathologies, while constitutional tall stature is more often
associated with a normal bone age; however, the sensitivity and

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Fig. 3. Diagnostic chart of tall stature.

Adapted from [5].

specificity of bone age for diagnosis have not been specifically
evaluated, and are likely to be very low. The interest of bone age
measurement or the determination of the height prognosis will
be discussed in the chapter by T. Edouard [2].
The diagnostic approach is to determine if the tall stature
is pathological or physiological (the latter is by far the most
frequent), to assess the organic and psychological conse-
quences of tall stature, and to assess the height prognosis
(the therapeutic modalities will be detailed in the chapter by
T. Edouard).
2. The main causes of tall stature
The main causes of tall stature, and the synthetic diagnos-
tic approach, are shown in Fig. 3. The diagnostic approach is
based on the study of the growth rate (normal or accelerated),
birth data (excess in foetal growth?), and the search for dysmor-
phia/disproportion/slow development. It is not in the objective
of this article to comprehensively summarise all aetiologies: we
cover the main ones [5].
2.1. Constitutional tall stature
Constitutional tall stature is a diagnosis of elimination, but it
is the most common [1,5]. Tall stature is usually present at birth
in tall stature families. The growth curve often shows accelerated
growth during the first years of life, then a stabilisation between
3 and 5 years on a growth corridor beyond +2SD. Bone age is
most often aligned with actual age. The hormonal balance is
normal, even if circulating IGF1 levels can sometimes be in the
upper half of the normal for the age and sex, the GH suppression
in response to an oral glucose tolerance test can be imperfect in
adolescence in particular, and the sensitivity to the growth hor-
mone can be increased [6]. If the child has a height > +2 standard
deviations from the genetic target height and levels of circulat-
ing IGF-1 also close to +2 SD score, carrying out an OGTT
and a cranial MRI is useful, in order to eliminate acromegaly.
A variant of constitutional tall stature is constitutional advanced
growth: the auxological characteristics are the same as those of
the constitutional tall stature, but bone age is advanced, and the
entire aetiological balance is negative.
2.2. Acromegalogigantism
Acromegalogigantism is very rare in paediatrics, due to a
somatotroph adenoma (or hyperplasia of the somatotroph cells).
The clinical presentation shows generally a pathological accel-
erated growth and not necessarily other clinical manifestations
(large features, enlargement of the nose and chin, thick skin,
large and wide limbs). Biologically, circulating IGF1 levels are,
in virtually all cases reported, very high for the age (higher
than +2 SD score), with circulating basal GH levels being easily
detectable (often greater than 15 ␮g/L), and GH secretion of GH
not suppressed during the OGTT. The pituitary MRI confirms the
diagnosis [7]. In adolescence, it may sometimes be difficult to
discriminate a physiological elevation of IGF-1 of a pathological
elevation (MRI is useful in case of doubt). Finally, in McCune-
Albright syndrome, one can observe a defect in GH suppression
during OGTT contrasting with circulating IGF-1 levels in the
limits of the normal, little growth advance (due to the bone dis-
ease), and advanced bone age (due to the gonadal and adrenal
autonomy)[8]. Somatotroph adenomas represent 1–20% of child
pituitary tumours, which represent less than 3% of supratentorial
child tumours. A molecular cause must be sought systematically:

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McCune-Albright syndrome, MEN1, AIP mutation, GPR101 2.5. Marfan syndrome

mutations, Carney complex [8–11].
2.3. Early puberty and early pseudopuberty
Early puberty and early pseudopuberty lead to growth
advance and advanced bone age, and the emergence of sec-
ondary sexual characteristics. Investigations will highlight the
origin of excess production of androgens/oestrogens (adrenal
tumour, adrenal hyperplasia, peripheral early puberty, central
early puberty, hCG tumour, exogenous exposure). They will be
not detailed in this chapter.
Marfan syndrome (1/5000 to 1/10,000) is a systemic pathol-
ogy of the connective tissue of dominant autosomal inheritance
(mutation of the NBF1 gene). The growth is excessive with
dolichostenomelia as a trait (excessive growth of limbs) giv-
ing an arm span/height ratio greater than 1.05. The clinical
symptoms are pectus excavatum, tall stature, stretch marks,
arachnodactyly, and hyperlaxity. Various diagnostic criteria have
been established (Table 1). In addition to skeletal disorders, there
are heart (dilatation of the aorta with risk of dissection) and
ophthalmologic (ectopia of the lens) problems.
2.6. Sotos syndrome

2.4. Excess weight Sotos syndrome (1/14,000) is a pathology of autosomal dom-

Excess weight is usually associated with accelerated growth.
This accelerated growth can go up to one standard deviation in
pre-puberty for an excess of weight up to 150% of the ideal
weight for the size. Bone age is then moderately advanced in
relation to the actual age to a maximum of 1 to 2 years. When
accelerated growth is significant with advance of bone age of
more than 2 years, it is important to search for a cause other
than tall stature. Thus, optic pathway glioma (OPG) have been
associated with obesity, early pubertal development, and also to
acromegaly (probably by hypothalamic activation of the GHRH)
[12].
inant inheritance (gene NSD1), often sporadic, combining tall
stature at birth with excessive growth, macrocephalia, facial
dysmorphism (bumps protruding from forehead, prognathism,
thinning hair in the fronto-parietal area), a delay of development
with school problems, epilepsy (25%), and increased tumour risk
(3%).
2.7. Beckwith-Wiedemann Syndrome
Beckwith-Wiedemann Syndrome (1/13,000) of autosomal
dominant inheritance (11p15), associates a large neonatal size
and an acceleration of the growth rate up to 6–7 years, and then

Table 1
The criteria diagnostics of Marfan syndrome.

Aortic root dilatation

Ectopia lentis
Wrist AND thumb sign–3 (Wrist OR thumb sign–1)
Pectus carinatum deformity–2 (pectus excavatum or chest asymmetry–1)
Hindfoot deformity–2 (plain pes planus–1)
Pneumothorax–2
Dural ectasia–2
Protrusio acetabuli–2
Reduced US/LS AND increased arm/height AND no severe scoliosis–1
Scoliosis or thoracolumbar kyphosis–1
Reduced elbow extension–1
Facial features (3/5)–1 (dolichocephaly, enophtalmos, downslanting palpebral
fissures, malar hyoplasia, retrognathia)
Skin striae–1
Myopia > 3 diopters–1
Mitral valve prolapse (all types)–1

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Table 2 is the most frequent diagnosis, to retain after having rejected

Diagnostic criteria of the Beckwith-Wiedemann syndrome. pathological tall statures. The therapeutic approach depends on
Major criteria the growth prognosis and psychological tolerance. It will be
Omphalocele/umbilical hernia addressed in the article by T. Edouard.
Macroglossia
Macrosomia
Indents/atrial fistulas
Disclosure of interest
Embryonic tumours
Hemihypertrophy The authors declare that they have no competing interest.
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Please cite this article in press as: Coutant R, et al. How to investigate a child with excessive growth? Ann Endocrinol (Paris) (2017),
http://dx.doi.org/10.1016/j.ando.2017.04.006