SHOX-related short stature

SHOX-related short stature is a primary bone dysplasia characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones. Patients present normal bone age with normal growth velocity.

This condition can be caused by haploinsufficiency of the short stature homeobox-containing gene (SHOX), which is located on the X chromosome. The SHOX deficiency can result from various genetic mutations, including deletions or duplications of the SHOX gene.

The symptoms of SHOX-related short stature may include:

• Short stature that is 2 standard deviations below the mean height for a given age and sex
• Normal bone age and growth velocity
• Absence of obvious skeletal abnormalities and other diseases

It's worth noting that SHOX-related short stature can be part of a spectrum of conditions, ranging from mild, non-specific short stature to more severe presentations such as Leri-Weill dyschondrosteosis.

References:

[10] - This condition is characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones. [12] - Patients present normal bone age with normal growth velocity. [13] - SHOX-related short stature is a primary bone dysplasia characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones.

SHOX-related short stature is a primary bone dysplasia characterized by a height that is 2 standard deviations below the corresponding mean height for a given age, sex and population group, in the absence of obvious skeletal abnormalities and other diseases and with normal developmental milestones.

Individuals with SHOX deficiency may show additional signs and symptoms, depending on the type of SHOX-related condition they have [1]. Some common clinical features include:

• Short stature: This is a primary characteristic of SHOX-related short stature, where an individual's height is significantly below the average for their age group [2].
• Mesomelia: This refers to the shortening of the lower portion of the arm and leg, which can be observed in some individuals with SHOX deficiency [5].
• Madelung deformity: This is a condition where the forearm bones are abnormally aligned, leading to a characteristic "bowing" appearance [6].
• Abnormal alignment of the radius and ulna: In some cases, the radius and ulna bones in the forearm may be misaligned, which can lead to discomfort or pain [5].

It's worth noting that not all individuals with SHOX deficiency will exhibit these symptoms, and the severity of the condition can vary widely from person to person [11]. Additionally, some people with short stature and changes in the SHOX gene have been found to have subtle skeletal abnormalities [8].

In adults with SHOX deficiency, the proportion of LWD (Leri-Weill dyschondrosteosis) versus short stature without features of LWD is not well defined [11]. However, it's clear that SHOX-related short stature can have a significant impact on an individual's quality of life and overall health.

References:

[1] Context result 1 [2] Context result 2 [5] Context result 5 [6] Context result 6 [8] Context result 8 [11] Context result 11

SHOX-related short stature can be diagnosed through various tests, which are aimed at confirming the presence of a genetic mutation in the SHOX gene.

Genetic Testing

The primary diagnostic test for SHOX-related short stature is genetic testing. This involves analyzing DNA samples from affected individuals to identify mutations or deletions in the SHOX gene [1]. Genetic testing can confirm a diagnosis of SHOX syndrome and rule out other potential causes of short stature [2].

Diagnostic Algorithm

A diagnostic algorithm has been proposed for evaluating short stature, which includes genetic evaluation as one of the steps [13]. This algorithm helps healthcare providers to determine the likelihood of SHOX-related short stature among other possible causes.

Other Diagnostic Tests

While not specific to SHOX-related short stature, other diagnostic tests may be performed to rule out other potential causes of short stature. These include:

• Endocrine and metabolic disorders [14]
• Idiopathic short stature (defined as a height below the third percentile for chronological age or minus 2 standard deviations of national height standards) [15]

Specialist Referrals

A pediatrician or primary care physician may refer patients to specialists, such as geneticists or orthopedic surgeons, for further evaluation and diagnosis. Diagnostic teams for SHOX-related short stature may include genetics, orthopedics, and other specialists [11].

In summary, diagnostic tests for SHOX-related short stature primarily involve genetic testing to confirm the presence of a mutation in the SHOX gene. Other diagnostic tests may be performed to rule out other potential causes of short stature.

References:

[1] Context result 5 [2] Context result 3 [11] Context result 11 [13] Context result 13 [14] Context result 14 [15] Context result 15

SHOX-related short stature is a condition characterized by a height that is significantly below the average height for a given age and sex, due to a deficiency in the SHOX gene. The primary treatment for this condition involves the use of recombinant human growth hormone (rhGH) therapy.

Treatment Options:

• Recombinant human growth hormone (rhGH) therapy has been approved by regulatory agencies such as the US FDA and is supported by clinical studies [8][9].
• This therapy involves daily injections of rhGH, which have been shown to improve final height in patients with SHOX deficiency [5][10].

Benefits:

• Studies have demonstrated that rhGH therapy can lead to a significant gain in final height, ranging from 7-10 cm [10].
• The therapeutic effect of rhGH has been observed to be similar in girls with Turner syndrome and children with SHOX deficiency [7].

Guidelines and Recommendations:

• The Pediatric Endocrine Society has published guidelines for the use of growth hormone (hGH) and insulin-like growth factor-I (hIGF-I) treatment for GH deficiency, idiopathic short stature (ISS), and primary IGF-I deficiency in children and adolescents [11].
• Currently, two specialty drugs—recombinant human GH (rhGH) and recombinant human IGF-1 (rhIGF-1)—are available to treat childhood short stature [12].

Conclusion:

Recombinant human growth hormone (rhGH) therapy is the primary treatment for SHOX-related short stature, with a significant gain in final height observed in clinical studies. This therapy has been approved by regulatory agencies and is supported by guidelines from professional societies.

References: [5] - [10] are citations from the provided context. [8] - Context result 8 [9] - Context result 9 [11] - Context result 11 [12] - Context result 12

The differential diagnosis of SHOX-related short stature involves identifying other conditions that may present with similar symptoms. According to various medical sources [1, 2, 3], the differential diagnosis includes:

• Turner syndrome in females
• Leri-Weill dyschondrosteosis (LWD), a condition characterized by short stature and skeletal abnormalities
• Idiopathic short stature, which is not associated with any underlying disease or syndrome
• Down syndrome (trisomy 21)
• Silver-Russell syndrome
• Hypochondroplasia
• SHOX gene mutations

It's essential to note that SHOX deficiency can cause a range of phenotypes, from mild non-specific short stature to severe Leri-Weill dyschondrosteosis [4]. In adults with SHOX deficiency, the proportion of LWD versus short stature without features of LWD is not well defined [5].

To accurately diagnose SHOX-related short stature, healthcare professionals may use biochemical and radiological tests, including anthropometric measurements to assess height and skeletal abnormalities [6]. The diagnosis requires a comprehensive evaluation of the individual's medical history, physical examination, and laboratory results.

References: [1] Binder G. (2011) [2] Fukami M. (2016) [3] Vannelli S. (2020) [4] SHOX deficiency disorders [5] Adults with SHOX deficiency [6] Diagnosis of short stature