Short stature
| Short stature | |
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| ICD-10 | E34.3 |
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| ICD-9 | 783.43 |
| DiseasesDB | 18756 |
| MedlinePlus | 003271 |
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ifrah Fatima, M.B.B.S[2]
Overview
Short stature is defined as a height more than 2 standard deviations below the mean for chronological age and sex. It corresponds to a linear height of less than the 3rd percentile. The most common causes of short stature are normal variants of growth like familial short stature and constitutional delay of growth and puberty.
Historical Perspective
[Disease name] was first discovered by [name of scientist], a [nationality + occupation], in [year]/during/following [event].
The association between [important risk factor/cause] and [disease name] was made in/during [year/event].
In [year], [scientist] was the first to discover the association between [risk factor] and the development of [disease name].
In [year], [gene] mutations were first implicated in the pathogenesis of [disease name].
There have been several outbreaks of [disease name], including -----.
In [year], [diagnostic test/therapy] was developed by [scientist] to treat/diagnose [disease name].
Classification
There is no established system for the classification of short stature. Based on the etiology, short stature may be classified into normal variants of growth or systemic pathological causes. Normal variants of growth include- [1]
- Familial short stature
- Constitutional delay of growth and puberty
- Small for gestational age with catch-up growth
- Idiopathic short stature
For more information about the pathological etiology, refer to causes below.
Pathophysiology
The exact pathogenesis of short stature is an interplay of many factors. Linear growth is determined by the factors affecting the growth plate cartilage of bones. [2][3]
- Genetic factors- GH gene (17q22), SHOX gene variants, Pit-gene mutations, Turner syndrome, Achondroplasia (FGF)[4]
- Hormones that promote growth-
- Hormones that inhibit growth plate cartilage-
- Paracrine factors- Fibroblast growth factor, parathyroid hormone-related protein
- Extracellular matrix proteins- Collagen, proteoglycans
Causes
The most common causes of short stature are the normal variants of growth- familial short stature and constitutional delay of growth and puberty. Normal variants of growth include-
- Familial short stature
- Constitutional delay of growth and puberty
- Idiopathic short stature
- Small for gestational age infants with catch-up growth
Pathological causes of short stature include- [6]
- Malnutrition
- Treatment with Glucocorticoids
- Endocrine causes-
- Genetic syndromes
- Systemic diseases-
- Gastrointestinal causes- Celiac disease, Inflammatory bowel disease (Crohn's disease), Malabsorption syndromes
- Pulmonary causes- Cystic fibrosis, obstructive diseases like bronchial asthma
- Cardiology causes- Untreated congenital heart diseases [7]
- Chronic Kidney Disease
- Malignancy
- Rheumatological causes- Idiopathic juvenile arthritis[8]
- Hematological causes- Sickle cell anemia
- Immunodeficiency- Immune deficiencies, HIV infection
- Infectious diseases- Parasitic infestations like Ascariasis, Enterobius.
- Environmental pollutants- Lead exposure [9]
Differentiating familial short stature from constitutional delay
| Feature | Familial short stature | Constitutional delay |
|---|---|---|
| Parents' height | Short | Normal or average |
| Growth | Normal | Slow |
| Bone age | Normal | Delayed |
| Puberty | Normal | Delayed |
| Adult height | Short | Normal |
Epidemiology and Demographics
The incidence of short stature according to its definition is approximately 2.5% i.e more than 2 standard deviations below the mean for chronological age and sex. The prevalence varies according to different environmental and genetic factors.
According to a study by Lindsay et al, the prevalence of growth hormone deficiency in the United States is 1: 1348. [12]
A study by Velayutham et al showed that the prevalence of short stature in school-going population in South India is 2.86%. [13]
According to a study by Mouzan et al, the prevalence of short stature ranged from 1.8% to 11.3% in males and 1.2% to 10.5% in females. [14]
There is no racial predilection to short stature.
Males are more commonly affected by short stature due to growth hormone deficiency.
Risk Factors
Common risk factors in the development of short stature include- [15][16][17]
- Genetic factors
- Environmental factors
- Diet- undernutrition during pregnancy, malnutrition of infants
- Low birth weight
- Low gestational age at birth
Screening
Linear height is measured serially and charted at every well-child visit. The growth pattern should be charted and height velocity must be noted. The infancy-childhood-puberty mathematical model may be used to detect abnormalities.[18][19]
- Infancy- Nutrition dependent; rapid linear growth of about 30-35cm
- Childhood- Growth hormone-dependent; linear growth with constant height velocity
- Puberty- Sex steroids and growth hormone; pubertal growth spurt at around age 10 for girls and age 12 for boys. [20]
Natural History, Complications, and Prognosis
If left untreated, short stature results in lower than normal adult height.
Diagnosis
Diagnostic Study of Choice
The diagnosis of short stature is based on the definition of a height more than 2 standard deviations(SD) below the mean for chronological age and sex. This corresponds to a height of less than 2.3rd percentile. Serial measurements of height and height velocity must be done at every well-child visit and a growth chart must be monitored. For infants less than 2 years of age, the length is measured lying down. For children more than 2 years of age, standing height is measured.
History and Symptoms
The majority of patients with short stature are diagnosed by serial measurements of height.
When short stature is associated with underlying pathology, history of the following may be seen-
- Premature birth, small for gestational age
- Malnutrition- Weight loss, loss of appetite
- Crohn's disease- Diarrhea, weight loss, rectal bleeding
- Immunodeficiency syndromes or cystic fibrosis- recurrent infections
- Hypothyroidism- Cold intolerance, weight gain, dry skin, constipation
- Cushing's syndrome- thin skin, striae, central obesity
- Asthma- chronic cough
- Arthralgia
- Chronic systemic illness
- Use of glucocorticoids
- Learning disability in developmental disorders
Physical Examination
Patients with short stature usually appear normal. If associated with underlying conditions, other features related to the underlying disease may be seen. The following features must be noted on physical examination- [21]
- Length or height plotted on a growth chart corresponding to age and sex
- Weight and weight-for-age
- Height velocity- measured in cm/year by calculating the difference in height with a time difference of at least 6 months
- Midparental height- Represents the potential or genetic target height [22]
- Boys- (father's height + mother's height + 13 cm)/2
- Girls- (father's height + mother's height − 13 cm)/2
- Bone age
- Delayed- Constitutional delay in growth and puberty, underlying systemic illness
- Normal- Familial short stature
- Advanced- Precocious puberty
- Adult height prediction
Other features suspicious of pathological causes of short stature may be associated with-
- Turner syndrome- webbed neck, low-set ears
- Malnutrition
- Celiac disease- oral ulcers, anal tags
- Cystic fibrosis- weight loss
Laboratory Findings
There are no specific diagnostic laboratory findings associated with short stature. Associated findings due to an underlying pathological illness may be seen. [23] [24] [25]
- Growth hormone deficiency- Low growth hormone; growth hormone provocative/stimualtion tests
- Low insulin-like growth factor 1 (IGF-1)
- Low thyroid hormone, high TSH- Hypothyroidism
- Karyotyping
- Immunoglobulin measurement- immunodeficiencies
- Positive IgA anti-tissue transglutaminase- Celiac disease
Electrocardiogram
An ECG may be helpful in the diagnosis of congenital heart disease as a cause of short stature.
X-ray
An x-ray is used to determine the bone age in the diagnosis of the cause of short stature.
Echocardiography or Ultrasound
Echocardiography/ultrasound may be helpful in the diagnosis of short stature when associated with congenital heart disease.
CT scan
There are no CT scan findings associated with short stature.
MRI
There are no MRI findings associated with short stature. An MRI may be useful when short stature is associated with growth hormone deficiency. Suggestive findings include absence of the anterior pituitary gland (empty sella), an ectopic posterior pituitary gland, and hypoplasia of the pituitary gland. [26] [27]
Other Imaging Findings
There are no other imaging findings associated with short stature.
Other Diagnostic Studies
There are no other diagnostic studies associated with short stature.
Treatment
Medical Therapy
The mainstay of treatment for short stature due to growth hormone deficiency is growth hormone replacement therapy. [28] [25]
- Recombinant human Growth hormone (rhGH)- Initial dosing and adjustments are based on weight, body surface area, growth response, and increase in height velocity.
- Dose- Starting recommended dose is 25 μg/kg/day up to 43 µg/kg/day
- Regular assessment with growth velocity and IGF-1 levels must be done every 6-12 months.
- Inadequate response [30]
- Height velocity <2 cm/year
- Change in height velocity with a standard deviation of less than <0.3/year during the first 6–12 months of therapy
Other pharmacologic medical therapies for other causes of short stature include- [25]
- Recombinant IGF-1
- Testosterone
- Aromatase inhibitors- Anastrazole, letrozole
- Estrogen
- GnRH analogs
Patients with an underlying disorder resulting in short stature should be treated for the disorder.
Surgery
Surgical intervention is not recommended for the management of short stature.
Primary Prevention
There are no established measures for the primary prevention of short stature. Adequate maternal nutrition during pregnancy is an important factor.
Secondary Prevention
There are no established measures for the secondary prevention of short stature.
References
- ↑ Rogol AD, Hayden GF (2014). "Etiologies and early diagnosis of short stature and growth failure in children and adolescents". J Pediatr. 164 (5 Suppl): S1–14.e6. doi:10.1016/j.jpeds.2014.02.027. PMID 24731744.
- ↑ Rimoin DL, Borochowitz Z, Horton WA (1986). "Short stature--physiology and pathology". West J Med. 144 (6): 710–21. PMC 1306754. PMID 2873688.
- ↑ Baron J, Sävendahl L, De Luca F, Dauber A, Phillip M, Wit JM; et al. (2015). "Short and tall stature: a new paradigm emerges". Nat Rev Endocrinol. 11 (12): 735–46. doi:10.1038/nrendo.2015.165. PMC 5002943. PMID 26437621.
- ↑ Hanew K, Tachibana K, Yokoya S, Fujieda K, Tanaka T, Igarashi Y; et al. (2006). "Clinical characteristics, etiologies and pathophysiology of patients with severe short stature with severe GH deficiency: questionnaire study on the data registered with the foundation for growth science, Japan". Endocr J. 53 (2): 259–65. doi:10.1507/endocrj.53.259. PMID 16618986.
- ↑ Nilsson O, Weise M, Landman EB, Meyers JL, Barnes KM, Baron J (2014). "Evidence that estrogen hastens epiphyseal fusion and cessation of longitudinal bone growth by irreversibly depleting the number of resting zone progenitor cells in female rabbits". Endocrinology. 155 (8): 2892–9. doi:10.1210/en.2013-2175. PMC 4098010. PMID 24708243.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Kaji M, Nishi Y (2006). "Lead and growth". Clin Pediatr Endocrinol. 15 (4): 123–8. doi:10.1297/cpe.15.123. PMC 4004863. PMID 24790332.
- ↑ Lanes R, Lee PA, Plotnick LP, Kowarski AA, Migeon CJ (1980). "Are constitutional delay of growth and familial short stature different conditions?". Clin Pediatr (Phila). 19 (1): 31–3. doi:10.1177/000992288001900105. PMID 7351094.
- ↑ 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.
- ↑ Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M (1994). "Utah Growth Study: growth standards and the prevalence of growth hormone deficiency". J Pediatr. 125 (1): 29–35. doi:10.1016/s0022-3476(94)70117-2. PMID 8021781.
- ↑ 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.
- ↑ El Mouzan MI, Al Herbish AS, Al Salloum AA, Foster PJ, Al Omer AA, Qurachi MM (2011). "Prevalence of short stature in Saudi children and adolescents". Ann Saudi Med. 31 (5): 498–501. doi:10.4103/0256-4947.84628. PMC 3183685. PMID 21911988.
- ↑ Amigo H, Bustos P (1995). "[Risk factors of short stature in Chilean school children from rural areas of high social vulnerability]". Arch Latinoam Nutr. 45 (2): 97–102. PMID 8729259.
- ↑ Matsumoto M, Nagano N, Awano H, Ohyama S, Fujioka K, Iwatani S; et al. (2019). "Incidence and Neonatal Risk factors of Short Stature and Growth Hormone treatment in Japanese Preterm Infants Born Small for Gestational Age". Sci Rep. 9 (1): 12238. doi:10.1038/s41598-019-48785-y. PMC 6706397 Check
|pmc=value (help). PMID 31439925. - ↑ Hussein A, Farghaly H, Askar E, Metwalley K, Saad K, Zahran A; et al. (2017). "Etiological factors of short stature in children and adolescents: experience at a tertiary care hospital in Egypt". Ther Adv Endocrinol Metab. 8 (5): 75–80. doi:10.1177/2042018817707464. PMC 5467802. PMID 28634534.
- ↑ Tse WY, Hindmarsh PC, Brook CG (1989). "The infancy-childhood-puberty model of growth: clinical aspects". Acta Paediatr Scand Suppl. 356: 38–43, discussion 44-5. doi:10.1111/j.1651-2227.1989.tb11238.x. PMID 2683573.
- ↑ Karlberg J (1989). "A biologically-oriented mathematical model (ICP) for human growth". Acta Paediatr Scand Suppl. 350: 70–94. doi:10.1111/j.1651-2227.1989.tb11199.x. PMID 2801108.
- ↑ Tanner JM, Davies PS (1985). "Clinical longitudinal standards for height and height velocity for North American children". J Pediatr. 107 (3): 317–29. doi:10.1016/s0022-3476(85)80501-1. PMID 3875704.
- ↑ Haymond M, Kappelgaard AM, Czernichow P, Biller BM, Takano K, Kiess W; et al. (2013). "Early recognition of growth abnormalities permitting early intervention". Acta Paediatr. 102 (8): 787–96. doi:10.1111/apa.12266. PMC 3738943. PMID 23586744.
- ↑ Cole TJ (2000). "A simple chart to identify non-familial short stature". Arch Dis Child. 82 (2): 173–6. doi:10.1136/adc.82.2.173. PMC 1718221. PMID 10648378.
- ↑ Maghnie M, Labarta JI, Koledova E, Rohrer TR (2017). "Short Stature Diagnosis and Referral". Front Endocrinol (Lausanne). 8: 374. doi:10.3389/fendo.2017.00374. PMC 5768898. PMID 29375479.
- ↑ Evans C, Gregory JW, All Wales Clinical Biochemistry Audit Group (2004). "The investigation of short stature: a survey of practice in Wales and suggested practical guidelines". J Clin Pathol. 57 (2): 126–30. doi:10.1136/jcp.2002.002238. PMC 1770205. PMID 14747433.
- ↑ 25.0 25.1 25.2 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. - ↑ Xu C, Zhang X, Dong L, Zhu B, Xin T (2017). "MRI features of growth hormone deficiency in children with short stature caused by pituitary lesions". Exp Ther Med. 13 (6): 3474–3478. doi:10.3892/etm.2017.4377. PMC 5450600. PMID 28587427.
- ↑ Kalina MA, Kalina-Faska B, Gruszczyńska K, Baron J, Małecka-Tendera E (2012). "Usefulness of magnetic resonance findings of the hypothalamic-pituitary region in the management of short children with growth hormone deficiency: evidence from a longitudinal study". Childs Nerv Syst. 28 (1): 121–7. doi:10.1007/s00381-011-1594-7. PMC 3252499. PMID 21935593.
- ↑ Grimberg A, DiVall SA, Polychronakos C, Allen DB, Cohen LE, Quintos JB; et al. (2016). "Guidelines for Growth Hormone and Insulin-Like Growth Factor-I Treatment in Children and Adolescents: Growth Hormone Deficiency, Idiopathic Short Stature, and Primary Insulin-Like Growth Factor-I Deficiency". Horm Res Paediatr. 86 (6): 361–397. doi:10.1159/000452150. PMID 27884013.
- ↑ Cohen P, Germak J, Rogol AD, Weng W, Kappelgaard AM, Rosenfeld RG; et al. (2010). "Variable degree of growth hormone (GH) and insulin-like growth factor (IGF) sensitivity in children with idiopathic short stature compared with GH-deficient patients: evidence from an IGF-based dosing study of short children". J Clin Endocrinol Metab. 95 (5): 2089–98. doi:10.1210/jc.2009-2139. PMID 20207829.
- ↑ Bang P, Ahmed SF, Argente J, Backeljauw P, Bettendorf M, Bona G; et al. (2012). "Identification and management of poor response to growth-promoting therapy in children with short stature". Clin Endocrinol (Oxf). 77 (2): 169–81. doi:10.1111/j.1365-2265.2012.04420.x. PMID 22540980.