Short Stature: Difference between revisions

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{{Infobox disease |
__NOTOC__
  Name          = Short stature |
  Image          = |
  Caption        = |
  DiseasesDB    = 18756 |
  ICD10          = {{ICD10|E|34|3|e|20}} |
  ICD9          = {{ICD9|783.43}} |
  ICDO          = |
  OMIM          = |
  MedlinePlus    = 003271 |
  eMedicineSubj  = |
  eMedicineTopic = |
  MeshID        = |
}}
{{SI}}
{{SI}}
{{CMG}}; {{AE}} {{AyeshaFJ}}
{{CMG}}; {{AE}} {{AyeshaFJ}}


{{SK}}
==Overview==
==Overview==
'''Short stature''' is characterized as a [[condition]] in which the [[height]] of the [[person]] in the 3rd percentile is the [[average]] [[height]] of the [[age]] , [[sex]], and [[population]] [[group]]. According to Ranke (1996), “[[Short stature]] is [[defined]] as a [[condition]] in which the [[height]] of an [[individual]] is two [[standard deviations]] (SD) below the corresponding [[mean]] [[height]] of a given [[age]], [[sex]] and [[population]] [[group]].” <ref name="pmid32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=32310491 | doi= | pmc= | url= }} </ref> <ref name="pmidPMID: 31855368">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 31855368 | doi= | pmc= | url= }} </ref>
'''Short stature''' is characterized as a [[condition]] in which the [[height]] of the [[person]] in the 3rd percentile is the [[average]] [[height]] of the [[age]] , [[sex]], and [[population]] [[group]]. According to Ranke (1996), “[[Short stature]] is [[defined]] as a [[condition]] in which the [[height]] of an [[individual]] is two [[standard deviations]] (SD) below the corresponding [[mean]] [[height]] of a given [[age]], [[sex]] and [[population]] [[group]].” <ref name="pmid32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=32310491 | doi= | pmc= | url= }} </ref> <ref name="pmidPMID: 31855368">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 31855368 | doi= | pmc= | url= }} </ref>
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====Disproportionate short stature (DSS)====
====Disproportionate short stature (DSS)====
Whereas in disproportionate [[short stature]] (DSS), the normal proportion of [[limbs]] and [[trunk]] [[height]]  is [[absent]], and the [[individual]] shows a great difference in their [[sitting]] and [[standing]] [[height]]. <ref name="pmidPMID: 32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32310491 | doi= | pmc= | url= }} </ref>
Whereas in disproportionate [[short stature]] (DSS), the normal proportion of [[limbs]] and [[trunk]] [[height]]  is [[absent]], and the [[individual]] shows a great difference in their [[sitting]] and [[standing]] [[height]]. <ref name="pmidPMID: 32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32310491 | doi= | pmc= | url= }} </ref>
== Pathophysiology ==
* [[Short stature]] may be [[normal]]; therefore a detailed [[family history]] of [[growth]] patterns and direct [[measurement]] of the parents is an important part of evaluating if the [[short stature]] is due to the [[genetic]] [[causes]] and potentials of the [[child]].<ref name="pmidPMID: 32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32310491 | doi= | pmc= | url= }} </ref>
* If the [[Short stature]] results from [[growth]] [[failure]] or [[premature]] closure of the [[epiphysial]] [[growth plates]], it [[secondary]] to a [[pathologic]] [[condition]] or due to an [[inherited]] [[disorder]]. Therefore, [[pathophysiology]] depends on the underlying [[cause]].<ref name="pmidPMID: 32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32310491 | doi= | pmc= | url= }} </ref>


==Causes==
==Causes==
=== Physiological causes pf short stature ===
=== Physiological causes of short stature ===
====Familial short stature====
====Familial short stature====
* In [[familial]] [[short stature]], [[individuals]] have low-normal [[height]] [[velocity]] throughout their life.<ref name="pmidPMID: 32644549">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32644549 | doi= | pmc= | url= }} </ref>
* In [[familial]] [[short stature]], [[individuals]] have low-normal [[height]] [[velocity]] throughout their life.<ref name="pmidPMID: 32644549">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32644549 | doi= | pmc= | url= }} </ref>
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====Constitutional delay of growth and puberty ====
====Constitutional delay of growth and puberty ====
====Idiopathic short stature====
* [[Constitutional delay]] of [[growth]] and [[puberty]] (CDGP) is also called [[constitutional]] [[short stature]] for [[pre-pubertal]] [[children]], results in [[childhood]] [[short stature]] but leads to relatively [[normal]] [[height]] in adulthood.<ref name="pmidPMID: 23087852">{{cite journal| author=Soliman AT, De Sanctis V| title=An approach to constitutional delay of growth and puberty. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 | issue= 5 | pages= 698-705 | pmid=PMID: 23087852 | doi=10.4103/2230-8210.100650 | pmc=3475892 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23087852  }} </ref>
* Idiopathic short stature (ISS) is a height below 2 standard deviations (SD) of the mean for age, in the absence of any endocrine, metabolic, or other causes.


These children have normal height velocity at the lower limit, with no evidence of any lab findings.
* [[Children]] are of [[normal]] [[size]] at [[birth]]. However, a [[severe]] and [[prolonged]] decrease in [[growth rate]] is observed starting at three to six months of [[age]].<ref name="pmidPMID: 23087852">{{cite journal| author=Soliman AT, De Sanctis V| title=An approach to constitutional delay of growth and puberty. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 | issue= 5 | pages= 698-705 | pmid=PMID: 23087852 | doi=10.4103/2230-8210.100650 | pmc=3475892 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23087852  }} </ref>


and no biochemical or other evidence for a specific growth-retarding condition, which implies normal results for endocrine screening tests, including those for growth hormone deficiency. Genome-wide studies indicate that the majority of the variation in adult height is explained by several hundred genetic variations, each with a small effect [8]. However, in a small proportion of the population, short stature is caused by specific genetic variations with large effect. As an example, emerging evidence suggests that variants in the SHOX gene (short stature homeobox) are responsible for 1 to 4 percent of individuals who would otherwise have been classified as having "idiopathic" short stature (see 'SHOX gene variants' below). In a study of 565 individuals with unexplained short stature, whole-exome sequencing was performed in 200 subjects and was able to identify a genetic cause in 21 percent of syndromic cases and in 14 percent of those with isolated short stature [9]. In addition to these genetic contributors to ISS, it appears that epigenetic changes may play a role in some cases of ISS. In one study, ISS was associated with increased methylation of two promoter regions for the insulin-like growth factor 1 (IGF-1) gene; these epigenetic changes are predicted to reduce the individual's sensitivity to growth hormone [10]. (See "Growth hormone insensitivity syndromes", section on 'Impaired IGF1 promoter function'.)
* By three or four years of age, [[children]] with CDGP usually are growing at a low-normal [[rate]]. The [[growth curve]] that remains below the third percentile for [[height]].<ref name="pmidPMID: 23087852">{{cite journal| author=Soliman AT, De Sanctis V| title=An approach to constitutional delay of growth and puberty. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 | issue= 5 | pages= 698-705 | pmid=PMID: 23087852 | doi=10.4103/2230-8210.100650 | pmc=3475892 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23087852  }} </ref>


Growth hormone therapy is approved in the United States for children with ISS, which is defined for this purpose by a more stringent threshold for height (below -2.25 SD of the mean, and a predicted adult height is <63 inches [160 cm] for males and <59 inches [150 cm] for girls). However, the use of growth hormone for this group of patients remains controversial. Studies have shown that consumer preferences (family concern) and clinician attitudes are important drivers of treatment decisions, independent of patient characteristics [11]. Treatment indications and efficacy are discussed in detail separately. (See "Growth hormone treatment for idiopathic short stature".)
* In addition [[children]] also have delayed [[pubertal]] maturation. This leads to a marked [[height]] discrepancy during the early teenage years compared with their peers but is followed by catch-up [[growth]] when they do enter [[puberty]]. The hallmark of CDGP is delayed skeletal age.<ref name="pmidPMID: 23087852">{{cite journal| author=Soliman AT, De Sanctis V| title=An approach to constitutional delay of growth and puberty. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 | issue= 5 | pages= 698-705 | pmid=PMID: 23087852 | doi=10.4103/2230-8210.100650 | pmc=3475892 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23087852  }} </ref>


ISS is a diagnosis of exclusion. The child's height percentile is below the range predicted by the mid-parental height and the bone age is not delayed, but there is no evidence of underlying genetic, systemic, or endocrine disease [12]. Although this may be a variant of normal growth, patients with this growth pattern warrant monitoring for the possibility of unrecognized underlying disease.
====Idiopathic short stature====
* [[Idiopathic]] [[short stature]] (ISS) is a [[height]] below 2 [[standard deviation]] (SD) of the mean for [[age]], in the [[absence]] of any [[endocrine]], [[metabolic]], or other [[causes]].<ref name="pmidPMID: 23745354">{{cite journal| author=Vlaski J, Katanić D, Privrodski JJ, Kavecan I, Vorguicn I, Obrenović M| title=[Idiopathic short stature]. | journal=Srp Arh Celok Lek | year= 2013 | volume= 141 | issue= 3-4 | pages= 256-61 | pmid=PMID: 23745354 | doi=10.2298/sarh1304256v | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23745354  }} </ref>


There is ongoing controversy about the nomenclature of ISS. Here, we use the term to refer to nonfamilial cases (ie, those without patterns of familial short stature). Others consider familial short stature and CDGP to be subcategories of ISS [12,13].
* These children are at the lower limit of the [[normal]] [[height]] [[velocity]], with normal [[lab]] [[findings]]. <ref name="pmidPMID: 23745354">{{cite journal| author=Vlaski J, Katanić D, Privrodski JJ, Kavecan I, Vorguicn I, Obrenović M| title=[Idiopathic short stature]. | journal=Srp Arh Celok Lek | year= 2013 | volume= 141 | issue= 3-4 | pages= 256-61 | pmid=PMID: 23745354 | doi=10.2298/sarh1304256v | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23745354  }} </ref>


====Small for gestational age infants with catch-up growth ====
====Small for gestational age infants with catch-up growth ====
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* About 10 percent of [[SGA]] [[infants]], particularly those born with more severe [[SGA]], do not experience catch-up [[growth]]. This group of [[SGA]]infants can be considered to have a pathologic pattern of growth. <ref name="pmidPMID: 11566651">{{cite journal| author=Fewtrell MS, Morley R, Abbott RA, Singhal A, Stephenson T, MacFadyen UM | display-authors=etal| title=Catch-up growth in small-for-gestational-age term infants: a randomized trial. | journal=Am J Clin Nutr | year= 2001 | volume= 74 | issue= 4 | pages= 516-23 | pmid=PMID: 11566651 | doi=10.1093/ajcn/74.4.516 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11566651  }} </ref>
* About 10 percent of [[SGA]] [[infants]], particularly those born with more severe [[SGA]], do not experience catch-up [[growth]]. This group of [[SGA]]infants can be considered to have a pathologic pattern of growth. <ref name="pmidPMID: 11566651">{{cite journal| author=Fewtrell MS, Morley R, Abbott RA, Singhal A, Stephenson T, MacFadyen UM | display-authors=etal| title=Catch-up growth in small-for-gestational-age term infants: a randomized trial. | journal=Am J Clin Nutr | year= 2001 | volume= 74 | issue= 4 | pages= 516-23 | pmid=PMID: 11566651 | doi=10.1093/ajcn/74.4.516 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11566651  }} </ref>


===PATHOLOGIC CAUSES OF GROWTH FAILURE===
=== Pathologic causes of short stature ===
====Systemic disorders with secondary effects on growth====
==== Systemic disorders with secondary effects on growth ====
* Undernutrition
===== Malnutrition =====
* Glucocorticoid therapy
* Malnutrition can lead to [[short stature]] with a delayed pattern of growth. The hallmark is low weight-for-height.
* Gastrointestinal disease  
 
* Rheumatologic disease
* Malnutrition can be due to inadequate food supply, or it may be due to an underlying condition which affects food intake or absorption or increases energy requirement of the body. <ref name="pmidPMID: 12522024">{{cite journal| author=Checkley W, Epstein LD, Gilman RH, Cabrera L, Black RE| title=Effects of acute diarrhea on linear growth in Peruvian children. | journal=Am J Epidemiol | year= 2003 | volume= 157 | issue= 2 | pages= 166-75 | pmid=PMID: 12522024 | doi=10.1093/aje/kwf179 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=12522024  }} </ref> <ref name="pmidPMID: 24353507">{{cite journal| author=Waqar Rabbani M, Imran Khan W, Bilal Afzal A, Rabbani W| title=Causes of short stature identified in children presenting at a tertiary care hospital in Multan Pakistan. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 1 | pages= 53-7 | pmid=PMID: 24353507 | doi=10.12669/pjms.291.2688 | pmc=3809182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353507  }} </ref>
* Chronic kidney disease
===== Glucocorticoid therapy =====
* Cancer  
* [[Glucocorticoids]] are used for the [[treatment]] of a variety of [[diseases]] in [[children]], such as [[asthma]], leading to [[growth failure]] in [[children]]. <ref name="pmidPMID: 24353507">{{cite journal| author=Waqar Rabbani M, Imran Khan W, Bilal Afzal A, Rabbani W| title=Causes of short stature identified in children presenting at a tertiary care hospital in Multan Pakistan. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 1 | pages= 53-7 | pmid=PMID: 24353507 | doi=10.12669/pjms.291.2688 | pmc=3809182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353507  }} </ref>
* Pulmonary disease  
 
* Cardiac disease
* [[Glucocorticoids]] can interfere with [[endogenous]] [[growth hormone]] [[secretion]] and action, [[bone]] [[formation]], [[nitrogen]] [[retention]], and [[collagen formation]]. <ref name="pmidPMID 8879994">{{cite journal| author=Allen DB| title=Growth suppression by glucocorticoid therapy. | journal=Endocrinol Metab Clin North Am | year= 1996 | volume= 25 | issue= 3 | pages= 699-717 | pmid=PMID 8879994 | doi=10.1016/s0889-8529(05)70348-0 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8879994  }} </ref>
* Immunologic disease
 
* Metabolic diseases  
* The [[growth effects]] of [[glucocorticoids]] are related to the [[type]], [[dose]], and [[duration]] of the [[exposure]]. If [[glucocorticoids]] are discontinued, [[children]] usually experience some catch-up growth. [[Growth impairment]] is more pronounced if it is given for a [[longer]] [[duration of action]] and when it is used daily as compared with an alternate-day [[regimen]].<ref name="pmidPMID: 24353507">{{cite journal| author=Waqar Rabbani M, Imran Khan W, Bilal Afzal A, Rabbani W| title=Causes of short stature identified in children presenting at a tertiary care hospital in Multan Pakistan. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 1 | pages= 53-7 | pmid=PMID: 24353507 | doi=10.12669/pjms.291.2688 | pmc=3809182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353507  }} </ref>
 
===== Gastrointestinal disease =====
* Some [[chronic]] [[gastrointestinal]] [[diseases]] such as [[Inflammatory bowel disease]] and [[celiac disease]] results in [[short stature]]. [[Children]] tend to have a greater [[decrease]] in [[weight]] than the [[height]] (ie, they are underweight-for-height).
 
* The [[growth failure]] is caused by the [[inflammatory]] [[disease]] process, as well as decreased [[food intake]], [[malabsorption]], or [[glucocorticoids]].
 
===== Rheumatologic disease =====
* [[Childhood]] [[rheumatologic diseases]], especially [[systemic juvenile idiopathic arthritis]], are frequently associated with [[growth retardation]].<ref name="pmidPMID 29940586">{{cite journal| author=de Zegher F, Reynaert N, De Somer L, Wouters C, Roelants M| title=Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies. | journal=Horm Res Paediatr | year= 2018 | volume= 90 | issue= 5 | pages= 337-343 | pmid=PMID 29940586 | doi=10.1159/000489778 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=29940586  }} </ref>
 
* This can be partly due to the [[inflammatory]] process driven by the [[proinflammatory]] [[cytokines]] and also caused by the high-dose [[glucocorticoids]] often used for [[management]].<ref name="pmidPMID 19940490">{{cite journal| author=Bechtold S, Roth J| title=Natural history of growth and body composition in juvenile idiopathic arthritis. | journal=Horm Res | year= 2009 | volume= 72 Suppl 1 | issue=  | pages= 13-9 | pmid=PMID 19940490 | doi=10.1159/000229758 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19940490  }} </ref>
 
===== Chronic kidney disease =====
* [[Growth failure]] is seen in at least one-third of [[children]] with [[chronic kidney disease]]. <ref name="pmidPMID: 18797585">{{cite journal| author=Oliveira JC, Siviero-Miachon AA, Spinola-Castro AM, Belangero VM, Guerra-Junior G| title=[Short stature in chronic kidney disease: physiopathology and treatment with growth hormone]. | journal=Arq Bras Endocrinol Metabol | year= 2008 | volume= 52 | issue= 5 | pages= 783-91 | pmid=PMID: 18797585 | doi=10.1590/s0004-27302008000500010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18797585  }} </ref>
 
* The [[primary]] [[causes]] of [[growth failure]] in [[children]] with [[chronic kidney disease]] are disturbances of [[growth hormone]] [[metabolism]] and its main [[mediator]], [[insulin-like growth factor 1]] ([[IGF-1]]). <ref name="pmidPMID: 18797585">{{cite journal| author=Oliveira JC, Siviero-Miachon AA, Spinola-Castro AM, Belangero VM, Guerra-Junior G| title=[Short stature in chronic kidney disease: physiopathology and treatment with growth hormone]. | journal=Arq Bras Endocrinol Metabol | year= 2008 | volume= 52 | issue= 5 | pages= 783-91 | pmid=PMID: 18797585 | doi=10.1590/s0004-27302008000500010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18797585  }} </ref>
 
*Other factors may include [[metabolic acidosis]], [[uremia]], poor [[nutrition]] secondary to [[dietary]] restrictions, [[anorexia]] of [[chronic]] illness, [[anemia]], [[calcium]] and [[phosphorus]] imbalance, renal osteodystrophy, or use of high-dose [[glucocorticoids]]. Affected [[patients]] are candidates for [[growth hormone]] [[therapy]] until [[renal transplantation]], and some of these [[patients]] may also benefit from [[growth hormone]] [[therapy]] after [[transplantation]]. <ref name="pmidPMID: 18797585">{{cite journal| author=Oliveira JC, Siviero-Miachon AA, Spinola-Castro AM, Belangero VM, Guerra-Junior G| title=[Short stature in chronic kidney disease: physiopathology and treatment with growth hormone]. | journal=Arq Bras Endocrinol Metabol | year= 2008 | volume= 52 | issue= 5 | pages= 783-91 | pmid=PMID: 18797585 | doi=10.1590/s0004-27302008000500010 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18797585  }} </ref> <ref name="pmidPMID: 16773402">{{cite journal| author=Mahan JD, Warady BA, Consensus Committee| title=Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement. | journal=Pediatr Nephrol | year= 2006 | volume= 21 | issue= 7 | pages= 917-30 | pmid=PMID: 16773402 | doi=10.1007/s00467-006-0020-y | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16773402  }} </ref>
 
===== Cancer =====
* [[Children]] with [[cancer]] have poor [[growth rate]] due to poor food intake, [[nausea]], [[vomiting]], and [[increased]] [[caloric]] [[utilization]].<ref name="pmidPMID 18059086">{{cite journal| author=Nandagopal R, Laverdière C, Mulrooney D, Hudson MM, Meacham L| title=Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group. | journal=Horm Res | year= 2008 | volume= 69 | issue= 2 | pages= 65-74 | pmid=PMID 18059086 | doi=10.1159/000111809 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18059086  }} </ref> <ref name="pmidPMID 2893877">{{cite journal| author=Clayton PE, Shalet SM, Morris-Jones PH, Price DA| title=Growth in children treated for acute lymphoblastic leukaemia. | journal=Lancet | year= 1988 | volume= 1 | issue= 8583 | pages= 460-2 | pmid=PMID 2893877 | doi=10.1016/s0140-6736(88)91246-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2893877  }} </ref>
 
* Also, [[anorexia]], [[nausea]], and [[vomiting]] induced by [[chemotherapy]] and [[radiotherapy]] also can contribute to impaired [[growth]].<ref name="pmidPMID 18059086">{{cite journal| author=Nandagopal R, Laverdière C, Mulrooney D, Hudson MM, Meacham L| title=Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group. | journal=Horm Res | year= 2008 | volume= 69 | issue= 2 | pages= 65-74 | pmid=PMID 18059086 | doi=10.1159/000111809 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18059086  }} </ref> <ref name="pmidPMID 2893877">{{cite journal| author=Clayton PE, Shalet SM, Morris-Jones PH, Price DA| title=Growth in children treated for acute lymphoblastic leukaemia. | journal=Lancet | year= 1988 | volume= 1 | issue= 8583 | pages= 460-2 | pmid=PMID 2893877 | doi=10.1016/s0140-6736(88)91246-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2893877  }} </ref>
 
===== Pulmonary disease =====
* In [[pulmonary diseases]], such as [[cystic fibrosis]], [[growth failure]] is caused by multiple mechanisms, including poor food intake, [[maldigestion]] or [[malabsorption]], [[chronic]] and [[recurrent]] [[infection]], and [[increased]] [[energy]] requirements.<ref name="pmidPMID 1872173">{{cite journal| author=Karlberg J, Kjellmer I, Kristiansson B| title=Linear growth in children with cystic fibrosis. I. Birth to 8 years of age. | journal=Acta Paediatr Scand | year= 1991 | volume= 80 | issue= 5 | pages= 508-14 | pmid=PMID 1872173 | doi=10.1111/j.1651-2227.1991.tb11894.x | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1872173  }} </ref>
 
* In [[asthma]], [[growth failure]] is usually due to the use of [[glucocorticoids]] for the [[treatment]]. <ref name="pmidPMID: 24353507">{{cite journal| author=Waqar Rabbani M, Imran Khan W, Bilal Afzal A, Rabbani W| title=Causes of short stature identified in children presenting at a tertiary care hospital in Multan Pakistan. | journal=Pak J Med Sci | year= 2013 | volume= 29 | issue= 1 | pages= 53-7 | pmid=PMID: 24353507 | doi=10.12669/pjms.291.2688 | pmc=3809182 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24353507  }} </ref>
 
===== Cardiac disease =====
* In [[severe]] [[congenital heart diseases]], [[growth failure]] is common. Sometimes, it is the presenting feature of the [[heart disease]].<ref name="pmidPMID 1623850">{{cite journal| author=Thommessen M, Heiberg A, Kase BF| title=Feeding problems in children with congenital heart disease: the impact on energy intake and growth outcome. | journal=Eur J Clin Nutr | year= 1992 | volume= 46 | issue= 7 | pages= 457-64 | pmid=PMID 1623850 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1623850  }} </ref>
 
* The major causes include, [[anorexia]] and increased basal energy requirements. <ref name="pmidPMID 1623850">{{cite journal| author=Thommessen M, Heiberg A, Kase BF| title=Feeding problems in children with congenital heart disease: the impact on energy intake and growth outcome. | journal=Eur J Clin Nutr | year= 1992 | volume= 46 | issue= 7 | pages= 457-64 | pmid=PMID 1623850 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1623850  }} </ref>
 
===== Immunologic disease =====
 
* Growth failure is associated with immunologic deficiencies such as common variable immunodeficiency or severe combined immunodeficiency syndrome, and infections such as HIV.<ref name="pmidPMID: 29763203">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 29763203 | doi= | pmc= | url= }} </ref>
 
===== Metabolic diseases =====
[[Metabolic disorders]] can lead to [[growth failure]] in [[children]] and [[adolescents]].
 
* The most common [[metabolic disorder]] in [[children]] is [[type 1 diabetes mellitus]]. It causes [[short stature]] and attenuated [[growth]] because of the [[caloric deficit]] resulting from severe [[glucosuria]]. Also,  [[type 1 diabetes]] causes a decrease in [[IGF-1]] production or action, which has a negative correlation with [[adult]] [[height]]. [[Diabetes]] with very poor [[glycemic]] control leads to [[Mauriac syndrome]], characterized by attenuated [[linear growth]], and delayed [[puberty]], [[hepatomegaly]], and [[Cushingoid]] features.
 
* [[Vitamin D]] [[deficiency]] can lead to [[rickets]] in [[children]] characterized by abnormal [[epiphyseal]] [[development]], bowing of the [[extremities]], and diminished [[growth]].
 
====Genetic Causes====  
====Genetic Causes====  
Several genetic disorders have prominent effects on growth.
Several genetic disorders have prominent effects on growth.
* Turner's Syndrome
* [[Turner's Syndrome]] <ref name="pmidPMID: 26191517">{{cite journal| author=Seo GH, Kang E, Cho JH, Lee BH, Choi JH, Kim GH | display-authors=etal| title=Turner syndrome presented with tall stature due to overdosage of the SHOX gene. | journal=Ann Pediatr Endocrinol Metab | year= 2015 | volume= 20 | issue= 2 | pages= 110-3 | pmid=PMID: 26191517 | doi=10.6065/apem.2015.20.2.110 | pmc=4504991 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26191517  }} </ref>
* SHOX gene variant
* [[SHOX]] [[gene variant]] <ref name="pmid17182655">{{cite journal| author=Rappold G, Blum WF, Shavrikova EP, Crowe BJ, Roeth R, Quigley CA | display-authors=etal| title=Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency. | journal=J Med Genet | year= 2007 | volume= 44 | issue= 5 | pages= 306-13 | pmid=17182655 | doi=10.1136/jmg.2006.046581 | pmc=2597980 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17182655  }} </ref>
*Prader-Willi Syndrome
* [[Prader-Willi Syndrome]] <ref name="pmidPMID: 16128248">{{cite journal| author=Monzavi R, Fefferman RA, Pitukcheewanont P| title=Prader-Willi syndrome and mosaic Turner's syndrome. | journal=J Pediatr Endocrinol Metab | year= 2005 | volume= 18 | issue= 7 | pages= 711-7 | pmid=PMID: 16128248 | doi=10.1515/jpem.2005.18.7.711 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16128248  }} </ref>
*Noonan syndrome
* [[Noonan syndrome]] <ref name="pmidPMID: 30335302">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 30335302 | doi= | pmc= | url= }} </ref>
*Silver-Russell syndrome  
* [[Silver-Russell syndrome]] <ref name="pmidPMID: 32310491">{{cite journal| author=| title=StatPearls | journal= | year= 2020 | volume=  | issue=  | pages=  | pmid=PMID: 32310491 | doi= | pmc= | url= }} </ref>
*Skeletal dysplasias/growth plate abnormalities
* [[Skeletal dysplasia]]/[[growth plate]] [[abnormalities]] <ref name="pmidPMID: 25905353">{{cite journal| author=Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K | display-authors=etal| title=Endotext | journal= | year= 2000 | volume=  | issue=  | pages=  | pmid=PMID: 25905353 | doi= | pmc= | url= }} </ref>


====Endocrine Causes====
====Endocrine Causes====
*Cushing syndrome  
* Cushing syndrome: [[Cushing syndrome]] results in [[increased]] [[glucocorticoids]] and is characterized by the combination of [[weight gain]] and [[growth retardation]], resulting in [[excessive]] [[weight]]-for-[[height]]. [[Glucocorticoids]] directly inhibits the development of [[epiphyseal]] [[cartilage]] in [[growing]] [[long bones]] resulting in [[growth retardation]].<ref name="pmidPMID: 24412141">{{cite journal| author=Lodish MB, Gourgari E, Sinaii N, Hill S, Libuit L, Mastroyannis S | display-authors=etal| title=Skeletal maturation in children with Cushing syndrome is not consistently delayed: the role of corticotropin, obesity, and steroid hormones, and the effect of surgical cure. | journal=J Pediatr | year= 2014 | volume= 164 | issue= 4 | pages= 801-6 | pmid=PMID: 24412141 | doi=10.1016/j.jpeds.2013.11.065 | pmc=3963265 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24412141  }} </ref>
*Hypothyroidism
 
*Growth hormone deficiency
*Hypothyroidism: [[Growth failure]] is an [[important]] feature of [[hypothyroidism]]. Due to [[hypothyroidism]], the [[bone]] [[age]] is delayed. However, it is a [[treatable]] and [[reversible]] cause of [[short stature]] as once it is identified and [[treated]], [[children]] achieve the [[normal]] [[growth]] [[potential]].<ref name="pmidPMID: 2445271">{{cite journal| author=Virmani A, Menon PS, Karmarkar MG, Kochupillai N, Seth V, Ghai OP | display-authors=etal| title=Evaluation of thyroid function in children with undiagnosed short stature in north India. | journal=Ann Trop Paediatr | year= 1987 | volume= 7 | issue= 3 | pages= 205-9 | pmid=PMID: 2445271 | doi=10.1080/02724936.1987.11748508 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2445271  }} </ref>
 
*Growth hormone deficiency: If growth hormone deficiency is [[congenital]], then [[postnatal]] [[growth failure]] along with delayed [[bone]] [[age]] is seen. The [[patient]] has very [[low]] [[serum]] [[concentrations]] of [[growth hormone]], [[IGF-1]], and [[IGF-binding protein-3]] (IGFBP-3. Additional findings are [[hypoglycemia]], prolonged [[jaundice]], and [[micropenis]] in [[boys]], especially if [[gonadotropins]] are deficient as well. In [[children]], whose [[height]] may still be within the [[normal]] range for [[age]], has less severe [[growth failure]]. [[Acquired]] or secondary [[growth hormone]] [[deficiency]] occurs in case of [[intracranial]] [[tumor]] (eg, [[craniopharyngioma]]), [[cranial]] [[irradiation]], and [[head]] [[trauma]].<ref name="pmidPMID: 31514194">{{cite journal| author=Collett-Solberg PF, Ambler G, Backeljauw PF, Bidlingmaier M, Biller BMK, Boguszewski MCS | display-authors=etal| title=Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective. | journal=Horm Res Paediatr | year= 2019 | volume= 92 | issue= 1 | pages= 1-14 | pmid=PMID: 31514194 | doi=10.1159/000502231 | pmc=6979443 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31514194  }} </ref>


===Other causes of short stature===
*
===Psychosocial short stature===
===Psychosocial short stature===
It is a growth disorder that is observed between the ages of 2 and 15, caused by extreme emotional deprivation or stress.
It is a [[growth disorder]] that is observed between the ages of 2 and 15, caused by extreme [[emotional]] deprivation or [[stress]] which causes [[decrease]] in [[growth hormone]] ([[GH]]) and [[somatomedin]] [[secretion]], resulting in very [[short stature]]. Patient's [[weight]] is inappropriate for the [[height]] with immature [[skeletal]] age. <ref name="pmidPMID: 1524559">{{cite journal| author=Blizzard RM, Bulatovic A| title=Psychosocial short stature: a syndrome with many variables. | journal=Baillieres Clin Endocrinol Metab | year= 1992 | volume= 6 | issue= 3 | pages= 687-712 | pmid=PMID: 1524559 | doi=10.1016/s0950-351x(05)80119-3 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=1524559  }} </ref>
 
The symptoms include decreased growth hormone (GH) and somatomedin secretion, very short stature, weight that is inappropriate for the height, and immature skeletal age. This disease is a progressive one, and as long as the child is left in the stressing environment, their cognitive abilities continue to degenerate. Though rare in the population at large, it is common in feral children and in children kept in abusive, confined conditions for extended lengths of time. It can cause the body to completely stop growing but is generally considered to be temporary; regular growth will resume when the source of stress is removed


==Differential Diagnosis==
==Differential Diagnosis==
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== Diagnosis ==
== Diagnosis ==
===Diagnostic Criteria===
===Diagnostic Criteria===
*The diagnosis of [disease name] is made when at least [number] of the following [number] diagnostic criteria are met:
*The diagnostic criteria of [[short stature]] is when the [[height]] is 2 or more standard deviations below the mean for age and [[gender]] within a population (below the 2.5th percentile).<ref name="pmidPMID: 8506669">{{cite journal| author=Musilová J, Kölbel F, Král J, Simper D, Michalová K| title=[Cardiovascular changes in Turner's syndrome]. | journal=Vnitr Lek | year= 1993 | volume= 39 | issue= 2 | pages= 198-202 | pmid=PMID: 8506669 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8506669  }} </ref>
:*[criterion 1]
 
:*[criterion 2]
:*[criterion 3]
:*[criterion 4]
=== Symptoms ===
=== Symptoms ===
*[Disease name] is usually asymptomatic.
* Symptoms of the short stature depend on the underlying cause.
*Symptoms of [disease name] may include the following:
 
:*[symptom 1]
:*[symptom 2]
:*[symptom 3]
:*[symptom 4]
:*[symptom 5]
:*[symptom 6]
=== Physical Examination ===
=== Physical Examination ===
*Patients with [disease name] usually appear [general appearance].
* Short stature can be diagnosed by [[Anthropometric]] measurements including [[height]] [[vertex]], body [[weight]], [[trunk]] [[height]], and [[limb]] [[length]] of an individual. These are assessed in relation to [[age]], sex, and population.<ref name="pmidPMID: 8506669">{{cite journal| author=Musilová J, Kölbel F, Král J, Simper D, Michalová K| title=[Cardiovascular changes in Turner's syndrome]. | journal=Vnitr Lek | year= 1993 | volume= 39 | issue= 2 | pages= 198-202 | pmid=PMID: 8506669 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8506669  }} </ref>
*Physical examination may be remarkable for:
 
:*[finding 1]
* In [[achondroplasia]], enlarged [[head]] with [[frontal]] bossing, depressed [[nasal bridge]], mid-[[face]] [[hypoplasia]] and [[skull]].<ref name="pmidPMID: 8506669">{{cite journal| author=Musilová J, Kölbel F, Král J, Simper D, Michalová K| title=[Cardiovascular changes in Turner's syndrome]. | journal=Vnitr Lek | year= 1993 | volume= 39 | issue= 2 | pages= 198-202 | pmid=PMID: 8506669 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8506669  }} </ref>
:*[finding 2]
:*[finding 3]
:*[finding 4]
:*[finding 5]
:*[finding 6]


=== Laboratory Findings ===
=== Laboratory Findings ===
*There are no specific laboratory findings associated with [disease name].
The laboratory studies used to assess the major causes of short stature include,
* [[Measurement]] of [[serum]] [[levels]] of [[insulin-like growth factor-I]] ([[IGF-I]]), formerly named [[somatomedin C]], and [[IGF binding protein-3]] ([[IGFBP-3]]). [[Measurement]] of [[serum]] [[levels]] of [[growth hormone]].<ref name="pmidPMID: 11577173">{{cite journal| author=Laron Z| title=Insulin-like growth factor 1 (IGF-1): a growth hormone. | journal=Mol Pathol | year= 2001 | volume= 54 | issue= 5 | pages= 311-6 | pmid=PMID: 11577173 | doi=10.1136/mp.54.5.311 | pmc=1187088 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=11577173  }} </ref>
 
* [[Karyotype]] for the [[genetic]] [[causes]] of the [[short stature]].<ref name="pmidPMID: 31737054">{{cite journal| author=Ye CJ, Stilgenbauer L, Moy A, Liu G, Heng HH| title=What Is Karyotype Coding and Why Is Genomic Topology Important for Cancer and Evolution? | journal=Front Genet | year= 2019 | volume= 10 | issue=  | pages= 1082 | pmid=PMID: 31737054 | doi=10.3389/fgene.2019.01082 | pmc=6838208 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=31737054  }} </ref>
 
* Other tests include, 
** [[CBC]] for [[hematologic]] [[diseases]].<ref name="pmid32955036">{{cite journal| author=Bi H, Wang G, Li Z, Zhou L, Zhang M, Ye J | display-authors=etal| title=Erratum: Long Noncoding RNA (lncRNA) Maternally Expressed Gene 3 (MEG3) Participates in Chronic Obstructive Pulmonary Disease through Regulating Human Pulmonary Microvascular Endothelial Cell Apoptosis. | journal=Med Sci Monit | year= 2020 | volume= 26 | issue=  | pages= e927410 | pmid=32955036 | doi=10.12659/MSM.927410 | pmc=7518006 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=32955036  }} </ref>
** [[Serum]] total [[thyroxine]] (total T4) and [[thyrotropin]] (TSH) levels to test for [[hypothyroidism]].<ref name="pmidPMID: 30215224">{{cite journal| author=Soh SB, Aw TC| title=Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility. | journal=Ann Lab Med | year= 2019 | volume= 39 | issue= 1 | pages= 3-14 | pmid=PMID: 30215224 | doi=10.3343/alm.2019.39.1.3 | pmc=6143469 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=30215224  }} </ref>
** [[Antiendomysial]] [[immunoglobulin]] A (IgA) and [[immunoglobulin G]] ([[IgG]]), [[transglutaminase]] [[IgG]], and [[antigliadin]] [[IgG]] [[titers]] for [[gluten enteropathy]]. [[Erythrocyte sedimentation rate]] for [[inflammatory bowel disease]].<ref name="pmidPMID: 16474109">{{cite journal| author=Vermeire S, Van Assche G, Rutgeerts P| title=Laboratory markers in IBD: useful, magic, or unnecessary toys? | journal=Gut | year= 2006 | volume= 55 | issue= 3 | pages= 426-31 | pmid=PMID: 16474109 | doi=10.1136/gut.2005.069476 | pmc=1856093 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16474109  }} </ref>
** [[Serum]] [[transferrin]] and [[pre-albumin]] [[concentrations]] for [[malnutrition]].<ref name="pmidPMID: 27174435">{{cite journal| author=Bharadwaj S, Ginoya S, Tandon P, Gohel TD, Guirguis J, Vallabh H | display-authors=etal| title=Malnutrition: laboratory markers vs nutritional assessment. | journal=Gastroenterol Rep (Oxf) | year= 2016 | volume= 4 | issue= 4 | pages= 272-280 | pmid=PMID: 27174435 | doi=10.1093/gastro/gow013 | pmc=5193064 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27174435  }} </ref>
** [[Sweat]] [[chloride]] [[test]] for [[cystic fibrosis]]. <ref name="pmidPMID: 16648884">{{cite journal| author=Mishra A, Greaves R, Massie J| title=The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era. | journal=Clin Biochem Rev | year= 2005 | volume= 26 | issue= 4 | pages= 135-53 | pmid=PMID: 16648884 | doi= | pmc=1320177 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16648884  }} </ref> <ref name="pmidPMID: 3331206">{{cite journal| author=Landon C, Rosenfeld RG| title=Short stature and pubertal delay in cystic fibrosis. | journal=Pediatrician | year= 1987 | volume= 14 | issue= 4 | pages= 253-60 | pmid=PMID: 3331206 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=3331206  }} </ref>


*A  [positive/negative] [test name] is diagnostic of [disease name].
*An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
*Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
===Electrocardiogram===
===Electrocardiogram===
There are no ECG findings associated with [disease name].
* In [[Noonan syndrome]], which is one of the [[genetic]] cause of [[short stature]], [[electrocardiogram]] ([[ECG]]) shows [[left axis deviation]], [[abnormal]] R/S ratio over the left [[precordium]], and an [[abnormal]] [[Q wave]]. <ref name="pmidPMID: 18270737">{{cite journal| author=Raaijmakers R, Noordam C, Noonan JA, Croonen EA, van der Burgt CJ, Draaisma JM| title=Are ECG abnormalities in Noonan syndrome characteristic for the syndrome? | journal=Eur J Pediatr | year= 2008 | volume= 167 | issue= 12 | pages= 1363-7 | pmid=PMID: 18270737 | doi=10.1007/s00431-008-0670-9 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18270737  }} </ref>
 
OR


An ECG may be helpful in the diagnosis of [disease name]. Findings on an ECG suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
* In [[Turner's Syndrome]], [[ECG]] findings include [[ectopic]] [[supraventricular]] and [[ventricular]] activity. <ref name="pmidPMID: 8506669">{{cite journal| author=Musilová J, Kölbel F, Král J, Simper D, Michalová K| title=[Cardiovascular changes in Turner's syndrome]. | journal=Vnitr Lek | year= 1993 | volume= 39 | issue= 2 | pages= 198-202 | pmid=PMID: 8506669 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=8506669  }} </ref>


===X-ray===
===X-ray===
There are no x-ray findings associated with [disease name].
* [[Xray]] [[anteroposterior]] view of [[left]] [[hand]] and [[wrist]] is done to assess the [[bone]] [[age]] in children with [[short stature]].
* [[Xray]] findings of longstanding untreated [[hypothyroidism]] include [[epiphyseal]] [[dysgenesis]]. The [[spine]] shows [[platyspondyly]] and [[thoraco-lumbar]] [[kyphosis]].<ref name="pmidPMID: 2763957">{{cite journal| author=Kao SC, Waziri MH, Smith WL, Sato Y, Yuh WT, Franken EA| title=MR imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia. | journal=AJR Am J Roentgenol | year= 1989 | volume= 153 | issue= 3 | pages= 565-9 | pmid=PMID: 2763957 | doi=10.2214/ajr.153.3.565 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2763957  }} </ref>


OR
=== Ultrasound===
 
* [[Ultrasound]] helps in evaluation of [[thyroid]] [[pathologies]], such as [[thyroid]] [[dysgenesis]], [[ectopic]] [[thyroid]] [[gland]], [[goiter]] or [[thyroid]] [[mass]]. <ref name="pmidPMID: 2763957">{{cite journal| author=Kao SC, Waziri MH, Smith WL, Sato Y, Yuh WT, Franken EA| title=MR imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia. | journal=AJR Am J Roentgenol | year= 1989 | volume= 153 | issue= 3 | pages= 565-9 | pmid=PMID: 2763957 | doi=10.2214/ajr.153.3.565 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2763957 }} </ref>
An x-ray may be helpful in the diagnosis of [disease name]. Findings on an x-ray suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no x-ray findings associated with [disease name]. However, an x-ray may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
 
===Echocardiography or Ultrasound===
There are no echocardiography/ultrasound  findings associated with [disease name].
 
OR
 
Echocardiography/ultrasound  may be helpful in the diagnosis of [disease name]. Findings on an echocardiography/ultrasound suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
 
OR
 
There are no echocardiography/ultrasound findings associated with [disease name]. However, an echocardiography/ultrasound  may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].


===CT scan===
===CT scan===
Line 197: Line 206:


===MRI===
===MRI===
There are no MRI findings associated with [disease name].
OR
[Location] MRI may be helpful in the diagnosis of [disease name]. Findings on MRI suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].
OR


There are no MRI findings associated with [disease name]. However, a MRI may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].
* [[MRI]] is the [[modality]] of choice for the evaluation of [[pituitary-hypothalamic axis]] (PHA) in order to identify [[Congenital hypopituitarism]] or [[brain tumor]], which can cause isolated [[growth hormone]] [[deficiency]] (IGHD) or multiple [[pituitary]] [[hormone]] [[deficiencies]] (MPHDs) leading to [[growth retardation]].<ref name="pmidPMID: 23087851">{{cite journal| author=Chaudhary V, Bano S| title=Imaging in short stature. | journal=Indian J Endocrinol Metab | year= 2012 | volume= 16 | issue= 5 | pages= 692-7 | pmid=PMID: 23087851 | doi=10.4103/2230-8210.100641 | pmc=3475891 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=23087851  }} </ref>


===Other Imaging Findings===
* In [[achondroplasia]], [[MRI]] [[brain]] reveals small base of the [[skull]], narrowed [[foramen magnum]], [[syringomyelia]], [[myelomalacia]], [[hydrocephalus]], and [[lumbar]] [[spinal stenosis]].<ref name="pmidPMID: 2763957">{{cite journal| author=Kao SC, Waziri MH, Smith WL, Sato Y, Yuh WT, Franken EA| title=MR imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia. | journal=AJR Am J Roentgenol | year= 1989 | volume= 153 | issue= 3 | pages= 565-9 | pmid=PMID: 2763957 | doi=10.2214/ajr.153.3.565 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=2763957  }} </ref>
There are no other imaging findings associated with [disease name].
 
OR
 
[Imaging modality] may be helpful in the diagnosis of [disease name]. Findings on an [imaging modality] suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].


=== Other Diagnostic Studies ===
=== Other Diagnostic Studies ===
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[[Category:Signs and symptoms]]
[[Category:Signs and symptoms]]
[[Category:Physical examination]]
[[Category:Physical examination]]
 
[[Category:Primary care]]
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{{WikiDoc Sources}}

Latest revision as of 17:42, 30 November 2020

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ayesha Javid, MBBS[2]

Synonyms and keywords:

Overview

Short stature is characterized as a condition in which the height of the person in the 3rd percentile is the average height of the age , sex, and population group. According to Ranke (1996), “Short stature is defined as a condition in which the height of an individual is two standard deviations (SD) below the corresponding mean height of a given age, sex and population group.” [1] [2]

Historical Perspective

  • In 1967 by Pierre Maroteaux was the first man to ever mention dwarfism.

Classification

There are two types of short stature,

Proportionate short stature (PSS)

Proportionate short stature (PSS) is when the person is small, but limbs and trunk height are in proportions. [5]

Disproportionate short stature (DSS)

Whereas in disproportionate short stature (DSS), the normal proportion of limbs and trunk height is absent, and the individual shows a great difference in their sitting and standing height. [5]

Pathophysiology

Causes

Physiological causes of short stature

Familial short stature

Constitutional delay of growth and puberty

  • In addition children also have delayed pubertal maturation. This leads to a marked height discrepancy during the early teenage years compared with their peers but is followed by catch-up growth when they do enter puberty. The hallmark of CDGP is delayed skeletal age.[7]

Idiopathic short stature

Small for gestational age infants with catch-up growth

  • About 10 percent of SGA infants, particularly those born with more severe SGA, do not experience catch-up growth. This group of SGAinfants can be considered to have a pathologic pattern of growth. [9]

Pathologic causes of short stature

Systemic disorders with secondary effects on growth

Malnutrition
  • Malnutrition can lead to short stature with a delayed pattern of growth. The hallmark is low weight-for-height.
  • Malnutrition can be due to inadequate food supply, or it may be due to an underlying condition which affects food intake or absorption or increases energy requirement of the body. [10] [11]
Glucocorticoid therapy
Gastrointestinal disease
Rheumatologic disease
Chronic kidney disease
Cancer
Pulmonary disease
Cardiac disease
  • The major causes include, anorexia and increased basal energy requirements. [20]
Immunologic disease
  • Growth failure is associated with immunologic deficiencies such as common variable immunodeficiency or severe combined immunodeficiency syndrome, and infections such as HIV.[21]
Metabolic diseases

Metabolic disorders can lead to growth failure in children and adolescents.

Genetic Causes

Several genetic disorders have prominent effects on growth.

Endocrine Causes

Psychosocial short stature

It is a growth disorder that is observed between the ages of 2 and 15, caused by extreme emotional deprivation or stress which causes decrease in growth hormone (GH) and somatomedin secretion, resulting in very short stature. Patient's weight is inappropriate for the height with immature skeletal age. [30]

Differential Diagnosis

Epidemiology and Demographics

In the United States, 2.5% of the population is short. [5] A study conducted on the school children age 4-16 years in the South Indian Population shows the overall prevalence of short stature was 2.86%.[32]

Gender

  • Short stature is equally prevalent among both males and females, but studies show that boys were admitted more than the girls. This could be due to the reason that males are more likely to be brought to medical attention because of the prevalence of social expectations and pressures as compared to the females.
  • On the other hand, in Rosario, Argentina, the higher prevalence was found in females (16.4%) than males (8.4%) (p<0.001).[21] The short stature in females was related to age, weight, and abdominal obesity.

Age

  • Different ethnic groups have different average statures, which are essential to take into consideration while comparing mean parameters.
  • Any individual who has not attained the union of epiphyseal plates, can get affected.

Race

Risk Factors

Diagnosis

Diagnostic Criteria

  • The diagnostic criteria of short stature is when the height is 2 or more standard deviations below the mean for age and gender within a population (below the 2.5th percentile).[34]

Symptoms

  • Symptoms of the short stature depend on the underlying cause.

Physical Examination

Laboratory Findings

The laboratory studies used to assess the major causes of short stature include,

Electrocardiogram

X-ray

Ultrasound

CT scan

There are no CT scan findings associated with [disease name].

OR

[Location] CT scan may be helpful in the diagnosis of [disease name]. Findings on CT scan suggestive of/diagnostic of [disease name] include [finding 1], [finding 2], and [finding 3].

OR

There are no CT scan findings associated with [disease name]. However, a CT scan may be helpful in the diagnosis of complications of [disease name], which include [complication 1], [complication 2], and [complication 3].

MRI

Other Diagnostic Studies

  • [Disease name] may also be diagnosed using [diagnostic study name].
  • Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].

Treatment

Medical Therapy

Surgery

Prevention

References

  1. ↑ "StatPearls". 2020. PMID 32310491 Check |pmid= value (help).
  2. ↑ "StatPearls". 2020. PMID 31855368 PMID: 31855368 Check |pmid= value (help).
  3. ↑ Pauli RM (2019). "Achondroplasia: a comprehensive clinical review". Orphanet J Rare Dis. 14 (1): 1. doi:10.1186/s13023-018-0972-6. PMC 6318916. PMID 30606190 PMID: 30606190 Check |pmid= value (help).
  4. ↑ Shiang R, Thompson LM, Zhu YZ, Church DM, Fielder TJ, Bocian M; et al. (1994). "Mutations in the transmembrane domain of FGFR3 cause the most common genetic form of dwarfism, achondroplasia". Cell. 78 (2): 335–42. doi:10.1016/0092-8674(94)90302-6. PMID 7913883 PMID: 7913883 Check |pmid= value (help).
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 "StatPearls". 2020. PMID 32310491 PMID: 32310491 Check |pmid= value (help).
  6. ↑ 6.0 6.1 6.2 "StatPearls". 2020. PMID 32644549 PMID: 32644549 Check |pmid= value (help).
  7. ↑ 7.0 7.1 7.2 7.3 Soliman AT, De Sanctis V (2012). "An approach to constitutional delay of growth and puberty". Indian J Endocrinol Metab. 16 (5): 698–705. doi:10.4103/2230-8210.100650. PMC 3475892. PMID 23087852 PMID: 23087852 Check |pmid= value (help).
  8. ↑ 8.0 8.1 Vlaski J, Katanić D, Privrodski JJ, Kavecan I, Vorguicn I, Obrenović M (2013). "[Idiopathic short stature]". Srp Arh Celok Lek. 141 (3–4): 256–61. doi:10.2298/sarh1304256v. PMID 23745354 PMID: 23745354 Check |pmid= value (help).
  9. ↑ 9.0 9.1 Fewtrell MS, Morley R, Abbott RA, Singhal A, Stephenson T, MacFadyen UM; et al. (2001). "Catch-up growth in small-for-gestational-age term infants: a randomized trial". Am J Clin Nutr. 74 (4): 516–23. doi:10.1093/ajcn/74.4.516. PMID 11566651 PMID: 11566651 Check |pmid= value (help).
  10. ↑ Checkley W, Epstein LD, Gilman RH, Cabrera L, Black RE (2003). "Effects of acute diarrhea on linear growth in Peruvian children". Am J Epidemiol. 157 (2): 166–75. doi:10.1093/aje/kwf179. PMID 12522024 PMID: 12522024 Check |pmid= value (help).
  11. ↑ 11.0 11.1 11.2 11.3 Waqar Rabbani M, Imran Khan W, Bilal Afzal A, Rabbani W (2013). "Causes of short stature identified in children presenting at a tertiary care hospital in Multan Pakistan". Pak J Med Sci. 29 (1): 53–7. doi:10.12669/pjms.291.2688. PMC 3809182. PMID 24353507 PMID: 24353507 Check |pmid= value (help).
  12. ↑ Allen DB (1996). "Growth suppression by glucocorticoid therapy". Endocrinol Metab Clin North Am. 25 (3): 699–717. doi:10.1016/s0889-8529(05)70348-0. PMID 8879994 PMID 8879994 Check |pmid= value (help).
  13. ↑ de Zegher F, Reynaert N, De Somer L, Wouters C, Roelants M (2018). "Growth Failure in Children with Systemic Juvenile Idiopathic Arthritis and Prolonged Inflammation despite Treatment with Biologicals: Late Normalization of Height by Combined Hormonal Therapies". Horm Res Paediatr. 90 (5): 337–343. doi:10.1159/000489778. PMID 29940586 PMID 29940586 Check |pmid= value (help).
  14. ↑ Bechtold S, Roth J (2009). "Natural history of growth and body composition in juvenile idiopathic arthritis". Horm Res. 72 Suppl 1: 13–9. doi:10.1159/000229758. PMID 19940490 PMID 19940490 Check |pmid= value (help).
  15. ↑ 15.0 15.1 15.2 Oliveira JC, Siviero-Miachon AA, Spinola-Castro AM, Belangero VM, Guerra-Junior G (2008). "[Short stature in chronic kidney disease: physiopathology and treatment with growth hormone]". Arq Bras Endocrinol Metabol. 52 (5): 783–91. doi:10.1590/s0004-27302008000500010. PMID 18797585 PMID: 18797585 Check |pmid= value (help).
  16. ↑ Mahan JD, Warady BA, Consensus Committee (2006). "Assessment and treatment of short stature in pediatric patients with chronic kidney disease: a consensus statement". Pediatr Nephrol. 21 (7): 917–30. doi:10.1007/s00467-006-0020-y. PMID 16773402 PMID: 16773402 Check |pmid= value (help).
  17. ↑ 17.0 17.1 Nandagopal R, Laverdière C, Mulrooney D, Hudson MM, Meacham L (2008). "Endocrine late effects of childhood cancer therapy: a report from the Children's Oncology Group". Horm Res. 69 (2): 65–74. doi:10.1159/000111809. PMID 18059086 PMID 18059086 Check |pmid= value (help).
  18. ↑ 18.0 18.1 Clayton PE, Shalet SM, Morris-Jones PH, Price DA (1988). "Growth in children treated for acute lymphoblastic leukaemia". Lancet. 1 (8583): 460–2. doi:10.1016/s0140-6736(88)91246-9. PMID 2893877 PMID 2893877 Check |pmid= value (help).
  19. ↑ Karlberg J, Kjellmer I, Kristiansson B (1991). "Linear growth in children with cystic fibrosis. I. Birth to 8 years of age". Acta Paediatr Scand. 80 (5): 508–14. doi:10.1111/j.1651-2227.1991.tb11894.x. PMID 1872173 PMID 1872173 Check |pmid= value (help).
  20. ↑ 20.0 20.1 Thommessen M, Heiberg A, Kase BF (1992). "Feeding problems in children with congenital heart disease: the impact on energy intake and growth outcome". Eur J Clin Nutr. 46 (7): 457–64. PMID 1623850 PMID 1623850 Check |pmid= value (help).
  21. ↑ "StatPearls". 2020. PMID 29763203 PMID: 29763203 Check |pmid= value (help).
  22. ↑ Seo GH, Kang E, Cho JH, Lee BH, Choi JH, Kim GH; et al. (2015). "Turner syndrome presented with tall stature due to overdosage of the SHOX gene". Ann Pediatr Endocrinol Metab. 20 (2): 110–3. doi:10.6065/apem.2015.20.2.110. PMC 4504991. PMID 26191517 PMID: 26191517 Check |pmid= value (help).
  23. ↑ Rappold G, Blum WF, Shavrikova EP, Crowe BJ, Roeth R, Quigley CA; et al. (2007). "Genotypes and phenotypes in children with short stature: clinical indicators of SHOX haploinsufficiency". J Med Genet. 44 (5): 306–13. doi:10.1136/jmg.2006.046581. PMC 2597980. PMID 17182655.
  24. ↑ Monzavi R, Fefferman RA, Pitukcheewanont P (2005). "Prader-Willi syndrome and mosaic Turner's syndrome". J Pediatr Endocrinol Metab. 18 (7): 711–7. doi:10.1515/jpem.2005.18.7.711. PMID 16128248 PMID: 16128248 Check |pmid= value (help).
  25. ↑ "StatPearls". 2020. PMID 30335302 PMID: 30335302 Check |pmid= value (help).
  26. ↑ Feingold KR, Anawalt B, Boyce A, Chrousos G, de Herder WW, Dungan K; et al. (2000). "Endotext". PMID 25905353 PMID: 25905353 Check |pmid= value (help).
  27. ↑ Lodish MB, Gourgari E, Sinaii N, Hill S, Libuit L, Mastroyannis S; et al. (2014). "Skeletal maturation in children with Cushing syndrome is not consistently delayed: the role of corticotropin, obesity, and steroid hormones, and the effect of surgical cure". J Pediatr. 164 (4): 801–6. doi:10.1016/j.jpeds.2013.11.065. PMC 3963265. PMID 24412141 PMID: 24412141 Check |pmid= value (help).
  28. ↑ Virmani A, Menon PS, Karmarkar MG, Kochupillai N, Seth V, Ghai OP; et al. (1987). "Evaluation of thyroid function in children with undiagnosed short stature in north India". Ann Trop Paediatr. 7 (3): 205–9. doi:10.1080/02724936.1987.11748508. PMID 2445271 PMID: 2445271 Check |pmid= value (help).
  29. ↑ Collett-Solberg PF, Ambler G, Backeljauw PF, Bidlingmaier M, Biller BMK, Boguszewski MCS; et al. (2019). "Diagnosis, Genetics, and Therapy of Short Stature in Children: A Growth Hormone Research Society International Perspective". Horm Res Paediatr. 92 (1): 1–14. doi:10.1159/000502231. PMC 6979443 Check |pmc= value (help). PMID 31514194 PMID: 31514194 Check |pmid= value (help).
  30. ↑ Blizzard RM, Bulatovic A (1992). "Psychosocial short stature: a syndrome with many variables". Baillieres Clin Endocrinol Metab. 6 (3): 687–712. doi:10.1016/s0950-351x(05)80119-3. PMID 1524559 PMID: 1524559 Check |pmid= value (help).
  31. ↑ Derrick KM, Gomes WA, Gensure RC (2018). "Incidence and Outcomes of Pituitary Microadenomas in Children with Short Stature/Growth Hormone Deficiency". Horm Res Paediatr. 90 (3): 151–160. doi:10.1159/000489456. PMID 30261514 PMID: 30261514 Check |pmid= value (help).
  32. ↑ Velayutham K, Selvan SSA, Jeyabalaji RV, Balaji S (2017). "Prevalence and Etiological Profile of Short Stature among School Children in a South Indian Population". Indian J Endocrinol Metab. 21 (6): 820–822. doi:10.4103/ijem.IJEM_149_17. PMC 5729667. PMID 29285442 PMID: 29285442 Check |pmid= value (help).
  33. ↑ Grimberg A, Feemster KA, Pati S, Ramos M, Grundmeier R, Cucchiara AJ; et al. (2011). "Medically underserved girls receive less evaluation for short stature". Pediatrics. 127 (4): 696–702. doi:10.1542/peds.2010-1563. PMC 3065076. PMID 21422085 PMID: 21422085 Check |pmid= value (help).
  34. ↑ 34.0 34.1 34.2 34.3 Musilová J, Kölbel F, Král J, Simper D, Michalová K (1993). "[Cardiovascular changes in Turner's syndrome]". Vnitr Lek. 39 (2): 198–202. PMID 8506669 PMID: 8506669 Check |pmid= value (help).
  35. ↑ Laron Z (2001). "Insulin-like growth factor 1 (IGF-1): a growth hormone". Mol Pathol. 54 (5): 311–6. doi:10.1136/mp.54.5.311. PMC 1187088. PMID 11577173 PMID: 11577173 Check |pmid= value (help).
  36. ↑ Ye CJ, Stilgenbauer L, Moy A, Liu G, Heng HH (2019). "What Is Karyotype Coding and Why Is Genomic Topology Important for Cancer and Evolution?". Front Genet. 10: 1082. doi:10.3389/fgene.2019.01082. PMC 6838208 Check |pmc= value (help). PMID 31737054 PMID: 31737054 Check |pmid= value (help).
  37. ↑ Bi H, Wang G, Li Z, Zhou L, Zhang M, Ye J; et al. (2020). "Erratum: Long Noncoding RNA (lncRNA) Maternally Expressed Gene 3 (MEG3) Participates in Chronic Obstructive Pulmonary Disease through Regulating Human Pulmonary Microvascular Endothelial Cell Apoptosis". Med Sci Monit. 26: e927410. doi:10.12659/MSM.927410. PMC 7518006 Check |pmc= value (help). PMID 32955036 Check |pmid= value (help).
  38. ↑ Soh SB, Aw TC (2019). "Laboratory Testing in Thyroid Conditions - Pitfalls and Clinical Utility". Ann Lab Med. 39 (1): 3–14. doi:10.3343/alm.2019.39.1.3. PMC 6143469. PMID 30215224 PMID: 30215224 Check |pmid= value (help).
  39. ↑ Vermeire S, Van Assche G, Rutgeerts P (2006). "Laboratory markers in IBD: useful, magic, or unnecessary toys?". Gut. 55 (3): 426–31. doi:10.1136/gut.2005.069476. PMC 1856093. PMID 16474109 PMID: 16474109 Check |pmid= value (help).
  40. ↑ Bharadwaj S, Ginoya S, Tandon P, Gohel TD, Guirguis J, Vallabh H; et al. (2016). "Malnutrition: laboratory markers vs nutritional assessment". Gastroenterol Rep (Oxf). 4 (4): 272–280. doi:10.1093/gastro/gow013. PMC 5193064. PMID 27174435 PMID: 27174435 Check |pmid= value (help).
  41. ↑ Mishra A, Greaves R, Massie J (2005). "The relevance of sweat testing for the diagnosis of cystic fibrosis in the genomic era". Clin Biochem Rev. 26 (4): 135–53. PMC 1320177. PMID 16648884 PMID: 16648884 Check |pmid= value (help).
  42. ↑ Landon C, Rosenfeld RG (1987). "Short stature and pubertal delay in cystic fibrosis". Pediatrician. 14 (4): 253–60. PMID 3331206 PMID: 3331206 Check |pmid= value (help).
  43. ↑ Raaijmakers R, Noordam C, Noonan JA, Croonen EA, van der Burgt CJ, Draaisma JM (2008). "Are ECG abnormalities in Noonan syndrome characteristic for the syndrome?". Eur J Pediatr. 167 (12): 1363–7. doi:10.1007/s00431-008-0670-9. PMID 18270737 PMID: 18270737 Check |pmid= value (help).
  44. ↑ 44.0 44.1 44.2 Kao SC, Waziri MH, Smith WL, Sato Y, Yuh WT, Franken EA (1989). "MR imaging of the craniovertebral junction, cranium, and brain in children with achondroplasia". AJR Am J Roentgenol. 153 (3): 565–9. doi:10.2214/ajr.153.3.565. PMID 2763957 PMID: 2763957 Check |pmid= value (help).
  45. ↑ Chaudhary V, Bano S (2012). "Imaging in short stature". Indian J Endocrinol Metab. 16 (5): 692–7. doi:10.4103/2230-8210.100641. PMC 3475891. PMID 23087851 PMID: 23087851 Check |pmid= value (help).
  46. ↑ Lanes R, González Briceño LG (2017). "Alternatives in the Treatment of Short Stature". Adv Pediatr. 64 (1): 111–131. doi:10.1016/j.yapd.2017.03.004. PMID 28688585 PMID: 28688585 Check |pmid= value (help).
  47. ↑ Cattaneo R, Villa A, Catagni M, Tentori L (1988). "Limb lengthening in achondroplasia by Ilizarov's method". Int Orthop. 12 (3): 173–9. doi:10.1007/BF00547160. PMID 3182120 PMID: 3182120 Check |pmid= value (help).
  48. ↑ Ottaviani G, Randelli P, Catagni MA (2005). "Segmental cement extraction system (SEG-CES) and the Ilizarov method in limb salvage procedure after total knee cemented prosthesis removal in a former osteosarcoma patient". Knee Surg Sports Traumatol Arthrosc. 13 (7): 557–63. doi:10.1007/s00167-004-0575-8. PMID 15660273 PMID: 15660273 Check |pmid= value (help).
  49. ↑ Stathis SL, O'Callaghan MJ, Williams GM, Najman JM, Andersen MJ, Bor W (1999). "Behavioural and cognitive associations of short stature at 5 years". J Paediatr Child Health. 35 (6): 562–7. doi:10.1046/j.1440-1754.1999.00427.x. PMID 10634984 PMID: 10634984 Check |pmid= value (help).
  50. ↑ Kranzler JH, Rosenbloom AL, Proctor B, Diamond FB, Watson M (2000). "Is short stature a handicap? A comparison of the psychosocial functioning of referred and nonreferred children with normal short stature and children with normal stature". J Pediatr. 136 (1): 96–102. doi:10.1016/s0022-3476(00)90057-x. PMID 10636982 PMID: 10636982 Check |pmid= value (help).
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