Brachydactyly C, short stature, and hip dysplasia.
Short stature may be a component of the brachydactyly C syndrome. A family is presented in which the propositus has brachydactyly C, short stature, and hip dysplasia.
Adolescent↗
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Analysis of Genetic Factors in a Family With Short Stature.
BACKGROUND: To elucidate the genetic underpinnings of short stature in a familial cohort of five individuals. METHODS: A family with a history of short stature from Zhongnan Hospital of Wuhan University was the subject of this study. Peripheral blood samples were collected from family members for whole exome sequencing and Sanger sequencing to identify genetic anomalies. RESULTS: The male proband, aged 3 years and 10 months, had significant growth retardation, with a height of 91 cm (< 3rd percentile) and a weight of 13 kg (< 3rd percentile). Whole exome sequencing identified a missense mutation in the COL1A2 gene (c.577G>A, p.Gly193Ser) with maternal inheritance. Sanger sequencing confirmed this mutation in the mother and half-sister. According to American College of Medical Genetics and Genomics (ACMG) guidelines, this variant was classified as likely pathogenic. Additionally, a heterozygous mutation in the GH1 gene (c.291+1G>A) was detected in the father and grandfather, contributing to the familial short stature phenotype. CONCLUSION: In this family, we identified that variants in the COL1A2 and the GH1 can each cause short stature. This reflects both the genetic consistency and complexity of short stature, which is highly dependent on comprehensive genetic testing.
Humans↗
Familial short stature: genetic architecture, risk stratification, and precision management.
BACKGROUND: Familial short stature (FSS) has traditionally been considered a benign growth pattern characterized by short stature clustering within families and has often been regarded as a normal variant of growth. However, recent advances in genomic technologies have demonstrated that a subset of children presenting with an FSS phenotype harbor identifiable monogenic variants, particularly in genes involved in growth plate development and skeletal growth. These findings challenge the traditional phenotype-based understanding of FSS and support an etiology-oriented diagnostic framework. OBJECTIVE: To summarize current knowledge regarding the genetic architecture of FSS, review existing clinical risk stratification frameworks for genetic evaluation, and evaluate available evidence regarding treatment outcomes across different genetic etiologies. METHODS: A literature search was performed in PubMed, Embase, and Web of Science from inception to May 2026, using keywords including "familial short stature," "familial idiopathic short stature," "genetic testing," "ACAN," "SHOX," and "NPR2". Relevant original studies and review articles addressing genotype-phenotype correlations, diagnostic yield of genetic testing, or responses to recombinant human growth hormone (rhGH) therapy were considered. RESULTS: Emerging evidence indicates that monogenic variants can be identified in a subset of children with an FSS phenotype, especially among those with more severe short stature and autosomal dominant inheritance patterns. Variants affecting growth plate biology represent some of the most frequently reported genetic causes of FSS, with ACAN, SHOX, and NPR2 being the most frequently implicated genes. Existing clinical frameworks based on parental height patterns and inheritance characteristics may help stratify patients with FSS according to the likelihood of monogenic etiology and guide selection of individuals who may benefit from genetic testing. Available evidence suggests that rhGH therapy may improve growth outcomes in several monogenic forms of FSS, although treatment responses vary according to genetic etiology. CONCLUSIONS: FSS should be regarded as a heterogeneous clinical phenotype rather than a single diagnostic entity. Integration of existing clinical risk stratification approaches with molecular diagnosis may enable more precise identification of underlying genetic causes and facilitate individualized therapeutic decision-making. Future advances in FSS management will likely depend on precision medicine approaches linking phenotype, genotype, and treatment response.
Humans↗
Growth deceleration patterns in children with constitutional short stature: an aid to diagnosis.
A retrospective study of 263 children referred for evaluation of short stature revealed that 149 (56.7%) had constitutional short stature (CSS). A typical pattern of growth was observed in these children. As exemplified by 12 children who had complete serial growth measurements, exaggerated growth deceleration first became apparent between 3 and 6 months of age, was greatest in the first two years of life, and resulted in these children falling more than 2 SDs below the mean for height by 3 years of age. After 3 years of age, the growth rate of these children with CSS was essentially the same as that of normal children, and they ran parallel to the growth curve though below the third percentile. The importance of serial measurements and the growth chart is emphasized, and recommendations are made for the evaluation of short stature or abnormal growth deceleration in the first three years of life. Awareness of this typical pattern of growth in children without disease may aid the pediatrician in his evaluation of short stature and allow for watchful waiting when results of screening tests are normal.
Age Determination by Skeleton↗
Studies of anabolic steroids: v. effect of prolonged oxandrolone administration on growth in children and adolescents with uncomplicated short stature.
A total of 130 patients with uncomplicated short stature (4 to 17 years of age) were treated with oxandrolone, 0.25 mg/kg/day, for up to four years. Oxandrolone therapy resulted in a two-fold increase in mean growth velocity in the first six months of therapy and was an effective growth stimulant for the full four-year period. There was no overall adverse effect of oxandrolone on post-treatment mean growth velocity or on skeletal maturation relative to height gain. There were 37 patients with greater increase in height age than bone age and 22 patients with greater increase in bone age than height age. Assessment of the contribution of oxandrolone therapy to the latter group is difficult because of inadequate methodology and the wide variation in individual growth patterns. Taken in their entirety, the data suggest that oxandrolone is useful in the prolonged treatment of uncomplicated short stature and is not associated with undesirable acceleration of skeletal maturation.
Adolescent↗
Comparison of physiological and pharmacological tests of growth hormone function in children with short stature.
We studied 30 short-statured children to investigate their 24-h integrated serum concentration of GH (ICGH) and its diurnal pattern and to compare this data with their responses to standard stimulation tests for GH release. Eight patients with normal stimulation tests had a mean (+/- SD) ICGH value of 8.0 +/- 3.8 ng/ml (range, 4.5--16.4), and all had several secretory peaks greater than 12 ng/ml. Nineteen patients with abnormal responses (peak, less than 10 ng/ml) had a mean ICGH value of 2.7 +/- 1.9 ng/ml (range, less than 0.8 to 7.0); this was significantly lower than that of control subjects and patients with normal stimulation tests. However, 5 of these patients had normal ICGH values. Three patients with borderline stimulation test responses (10--12 ng/ml) had normal ICGH values (3.2, 3.4, and 11.9 ng/ml). Of the 22 patients with either abnormal or borderline stimulation tests, 14 had an ICGH result below the range of normal. Of these 14, 11 had no secretory peaks greater than 10 ng/ml, whereas 3 had peaks between 10--12 ng/ml. The 8 other patients had ICGH results in the normal range. Despite significant correlation (r = 0.668), integrated GH values did not correlate with stimulation tests in a minority of the patients, the status of whom remains to be determined by long term response to exogenous GH therapy.
Adolescent↗
Partial short arm deletions of the X chromosome and spontaneous pubertal development in girls with short stature.
Five additional examples of partial deletion of the short arm of the X chromosome are reported. All of the patients had short stature. The presence of the other stigmata of Turner syndrome, including ovarian dysfunction, appeared to depend on the location of the deletion. Chromosomal analysis of girls with short stature (less than 140 cm), normal pubertal development, and regular menses may reveal that minor deletions of the short arm of the X chromosome are more frequent than has been previously reported.
Adolescent↗
[Plasma LH, FSH, TSH, prolactin and cortisol during a combined test of pituitary reserve in prepubertal subjects with short stature].
The effect of a combined test (insulin, TRH, LHRH) on plasma concentrations of LH, FSH, PRL, Cortisol was studied in 18 normal subjects in prepubescent state and in 65 patients in prepubescent state with short stature. In 6 subjects with short stature there was no change of LH, and in 7 subjects with short stature there was no change of FSH. In conclusion the combined test for pituitary stimulation provides an useful method for localizing the lesion in disorders of hypothalamo-pituitary axis.
Child↗
[Effect of the degree of short stature on the type of response to tests of pituitary growth hormone reserve].
Two HGH (insulin and L-Dopa) stimulating tests were performed at time interval on 65 subjects with short stature (SDs between -2 and -4.5 according to Tanner) and on 18 control subjects, in order to study the influence of short stature degree on the HGH behaviour during the stimulating tests. The results obtained show that: 1. Statistically the short stature degree does not affect the response to HGH stimulating tests. 2. Two tests are necessary to avoid erroneous diagnosis of dwarfism caused by lack of HGH. 3. No response to HGH stimulating tests in subjects with normal stature may prove a discrepancy between the hormone measured radioimmunologically and its biological action.
Body Height↗
High yield of monogenic short stature in children from Kurdistan, Iraq: A genetic testing algorithm for consanguineous families.
PURPOSE: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. METHODS: Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. RESULTS: A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. CONCLUSION: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.
Humans↗
Glucagon response to arginine in growth hormone deficient children before and after treatment with growth hormone and in children with non-endocrine short stature.
In order to assess the role of growth hormone in the modulation of alpha cell function, the plasma pancreatic glucagon response to intravenous arginine (0.5 g/kg) was determined in thirty-two children with non-endocrine short stature and in eighteen growth hormone deficient children. 60 min after arginine infusion, the growth hormone deficient children had significantly higher (P less than 0.05) plasma glucagon values than the children with non-endocrine short stature. Following short-term growth hormone therapy (2 iu qd or bid for 5 days) in eleven of these growth hormone deficient children, plasma pancreatic glucagon response to arginine was diminished, and there was a significantly (P less than 0.02) more rapid return to basal values than in the untreated group. The same trends persisted after long-term growth hormone therapy (2 iu three times per week for 12-30 months) in ten children but were not statistically significant. We conclude that growth hormone may play a role in modulating plasma pancreatic glucagon response. The persistent glucagon response to arginine noted in growth hormone deficient children might reflect a greater gluconeogenic stress imposed upon these children during fasting or decreased catabolism of glucagon in the growth hormone deficient state.
Adolescent↗
Urinary cyclic adenosine 3',5'-monophosphate excretion in children in short stature: effect of somatotropin.
Excretion of urinary cyclic adenosine 3',5'-monophosphate (cAMP) was determined in twenty-four children of short stature and in sixteen normal children. Of the patients, eight suffered from anterior panhypopituitarism, six from isolated deficiency or somatotropin, seven had a family history of short stature, and three had growth failure of pre-natal onset. In children suffering from anterior panhypopituitarism or from isolated somatotropin deficiency, excretion of cAMP was found to be depressed. Short-term administration of purified somatotropin in normal therapeutic dose (3.4 mg per 1.7 m2 i.m. daily for 5 days) had no effect on urinary cAMP, but reduced urine volume in all patient groups. During somatotropin treatment there was a positive correlation between changes in urine volume and nitrogen balance (r = 0.67).
Adolescent↗
46, X,X-X terminal rearrangement/45, X mosaicism in a child with short stature.
A phenotypically female child, investigated because of short stature, had abnormally large, often bipartite Barr bodies and a mosaicism of 45, X cells and cells with 46 chromosomes which included an exceptionally large metacentric chromosome (Xp+). G- and C-banding established that the chromosome was derived from two substantially entire X chromosomes joined short arm-to-short arm, and was likely to be an isodicentric X with functional inactivation of one centromere.
Body Height↗
[Morphological characteristics and the degree of somatic maturity in children of short stature].
An auxological investigation involved 199 children with short stature ( hypostatura simplex) in preschool and school age. The analysis of the material showed that eight anthropometrical patterns and five somatometric indices, with the evaluation of the level of skeletal maturity, were all lower in children under study in comparison to the mean growth standard for Warsaw children. In all features differences were statistically significant. The biggest differences however, were found in the length of the upper extremities and the trunk. Observed differences increase with age. The authors concluded that the children under study were harmoniously delayed in morphological age which was confirmed by the level of the index of biological maturity based on skeletal age. It was found that the level of biological maturation was delayed but not to such a great extent as in growth pathology.
Age Determination by Skeleton↗
An abnormal dicentric X chromosome in a patient with short stature and gonadal dysgenesis.
A 16 year-old girl with short stature and gonadal dysgenesis was found to have a chromosomal complement consisting of 46,X,dic(X) (qter yields p22::p22 yields qter). When comparing her clinical features with 7 other cases who appeared to have precisely the same abnormal dicentric X, it was found that even though the percent of 45,X cells present varied considerably from patient to patient, these patients were remarkably similar and the stigmata, of Turner's syndrome were minimal in this group as a whole.
Adolescent↗
Peripheral resistance to thyroxine: a cause of short stature in a boy without goitre.
A euthyroid pubertal boy was investigated for short stature and was found to have an elevated serum thyroxine and delayed bone age. In spite of high thyroxine levels, there were no clinical signs of hyperthyroidism and kinetic studies revealed a normal rate of thyroxine metabolism. Plasma TSH levels were elevated but there was no goitre. Administration of up to 900 mug of thyroxine or 225 mug of triiodothyronine led to minimal changes in urinary hydroxyproline excretion, pulse rate and body weight. These observations indicate that this boy has a target organ insensitivity to thyroid hormones. When compared with other patients with this disorder, the studies further emphasize that this condition may have a variable clinical presentation. In addition, the extent of the target organ defect may not be evident from routine clinical and laboratory observations. The possible molecular basis of the defect is discussed.
Adolescent↗
A new syndrome of cleft palate associated with coloboma, hypospadias, deafness, short stature, and radial synostosis.
A new syndrome characterized by cleft palate, coloboma, hypospadias, deafness, short stature, and radial synostosis has been described. The family history suggests either an autosomal dominant mode of inheritance with limited expression in females or X-linkage. Other syndromes with similar phenotypes and modes of inheritance are discussed. The need for accurate and complete family histories in cases involving cleft palate and cleft lip/palate is discussed in relation to genetic counselling and recurrent risk estimates.
Abnormalities, Multiple↗
Familial syndrome of mental retardation, short stature, contractures of the hands, and genital anomalies.
Two teen-age XY brothers with mental retardation, short stature, obesity, genital abnormalities, and contractures of their hands are described. They have generalized osteoporosis and a history of frequent fractures. Their endocrinologic evaluation was normal except for mild glucose intolerance and delayed, but normal puberty. Although these brothers are similar to individuals with Prader-Willi syndrome, their unusual hand contractures, clinically significant osteoporosis, and lack of hypotonia indicate that they represent a different entity.
Adolescent↗