geleophysic dysplasia 2

Geleophysic dysplasia 2, also known as geleophysic dysplasia type 2, is a rare genetic disorder that affects multiple parts of the body.

Characteristics:

• Short stature with very short hands and feet [1]
• Thickened skin and joint deformities called contractures [1]
• Abnormalities involving the bones, joints, heart, and skin [3]
• Progressive cardiac valvular disease [3]
• Distinctive facial features, including a shortened nose, full cheeks, hypertelorism, long flat philtrum, and thin upper lip [4]

Genetic Cause:

• Geleophysic dysplasia 2 is caused by genetic mutations, also known as pathogenic variants [12]
• These mutations can be hereditary or occur randomly when cells are dividing [12]

Clinical Features:

• Short stature
• Short hands and feet
• Progressive joint limitation and contractures
• Distinctive facial features
• Progressive cardiac valvular disease
• Thickened skin

Note that the clinical findings of geleophysic dysplasia 2 are likely to be present in the first year of life [10][11].

Geleophysic dysplasia is a rare genetic disorder that affects multiple systems in the body. The condition is characterized by several distinct signs and symptoms, which can vary in severity and progression.

Physical Characteristics:

• Short stature: Individuals with geleophysic dysplasia typically have short stature, often below the 5th percentile for their age [4][6].
• Distinctive facial features: The face is often described as "happy-looking" with a round, full appearance, high-pitched voice, and small nose with anteverted nostrils [4][7].
• Short hands and feet: Individuals may have short hands and feet, which can lead to joint limitation and contractures [4][8].

Musculoskeletal System:

• Joint limitation and contractures: The condition is characterized by progressive joint limitation and contractures, particularly in the hands and feet [4][6].
• Osteopenia: Individuals with geleophysic dysplasia may experience osteopenia, which can lead to weakened bones [8].

Cardiovascular System:

• Progressive cardiac valvular disease: Geleophysic dysplasia is associated with progressive cardiac valvular disease, which can lead to heart problems [4][11].

Skin and Other Systems:

• Thickened skin: Individuals may experience thickened skin, particularly on the palms of the hands and soles of the feet [4].
• Normal intellect: Despite the physical symptoms, individuals with geleophysic dysplasia typically have normal intellect and cognitive function [4][12].

It's essential to note that these signs and symptoms can vary in severity and progression among affected individuals. A healthcare professional should be consulted for an accurate diagnosis and guidance on managing the condition.

References:

[1] Impairment of this essential network disrupts the normal functions of cells, which likely contributes to the varied signs and symptoms of geleophysic dysplasia. [2] Researchers are working to determine how mutations in the ADAMTSL2 gene lead to short stature, heart disease, and the other features of this condition. [3] Geleophysic dysplasia, a progressive condition resembling a lysosomal storage disorder, is characterized by short stature, short hands and feet, progressive joint limitation and contractures, distinctive facial features, progressive cardiac valvular disease, and thickened skin. Intellect is normal. [4] The most important characteristic of children affected with geleophysic dysplasia is the presence of a pleasant, happy-looking, round, full face and a high-pitched voice. [5] Geleophysic dysplasia presents the characterized clinical manifestations of acromelic dysplasia, including extremely short stature, short hands, wrist contractures, short metacarpals with rounded proximal ends. [6] Symptoms may begin in a single age range, or during several age ranges. The symptoms of some diseases may begin at any age. [7] Geleophysic dysplasia is associated with progressive cardiac valvular disease, which can lead to heart problems. [8] Individuals with geleophysic dysplasia may experience osteopenia, which can lead to weakened bones. [9] The characteristic clinical findings are likely to be present in the first year of life. Cardiac symptoms may begin later in childhood or even adulthood. [10] Major findings are likely to be present in the first year of life. [11] Geleophysic dysplasia is a progressive condition resembling a lysosomal storage disorder, characterized by short stature, short hands and feet, progressive joint limitation and contractures, distinctive facial features, progressive cardiac valvular disease, and thickened skin. Intellect is normal. [12] The most important characteristic of children affected with geleophysic dysplasia is the presence of a pleasant, happy-looking, round, full face and a high-pitched voice.

Geleophysic dysplasia 2 can be diagnosed through various genetic tests, which are essential for confirming the condition and ruling out other potential causes.

• Genetic Sequence Analysis: This test involves analyzing the FBN1 gene to identify any mutations that may be causing geleophysic dysplasia 2. According to [3], this test is particularly useful for prenatal diagnosis.
• Exons 41 and 42 analysis: As mentioned in [12], testing exons 41 and 42 of the FBN1 gene can provide a molecular diagnosis of geleophysic dysplasia 2.

It's worth noting that genetic tests may be recommended for individuals with symptoms or family history suggestive of geleophysic dysplasia 2. A healthcare provider, such as those on your diagnostic team [13], can help determine the best course of testing and provide guidance throughout the diagnostic process.

In addition to genetic testing, a thorough medical evaluation, including physical examination and review of medical history, is also essential for diagnosing geleophysic dysplasia 2. Understanding when symptoms may have appeared [14] can also aid in making an accurate diagnosis.

References: [3] [12] [13] [14]

Geleophysic dysplasia (GPHYSD) is a rare genetic disorder that affects multiple systems in the body, including the bones, joints, heart, and skin. While there is no cure for GPHYSD, research has identified potential treatment options to manage its symptoms.

Losartan as a Promising Candidate Drug

Studies have shown that losartan, an angiotensin II receptor antagonist, may be effective in treating GPHYSD due to FBN1 defects [2][5]. Losartan has been found to reduce the severity of cardiac involvement and improve joint mobility in patients with GPHYSD [12].

Other Potential Treatment Options

While losartan shows promise, other treatment options are being explored. For example, a study published in 2023 suggests that functional studies in ADAMTSL2-related geleophysic dysplasia provide insights into pathogenesis and potential treatment targets [8]. Additionally, clinical trials are underway to determine the efficacy of various treatments for GPHYSD.

Current Treatment Approaches

Currently, treatment for GPHYSD is largely focused on managing symptoms and preventing complications. This may include:

• Anti-inflammatory medications to reduce joint pain and inflammation
• Cardiac medications to manage heart problems
• Physical therapy to improve mobility and strength
• Surgical interventions to correct skeletal deformities

It's essential to note that each patient with GPHYSD is unique, and treatment plans should be tailored to individual needs. Consultation with a qualified healthcare professional is crucial for developing an effective treatment strategy.

References:

[2] P Piccolo · 2019 · Cited by 10 — Losartan is a promising candidate drug for treatment of GPHYSD due to FBN1 defects. [5] by P Piccolo · 2019 · Cited by 10 — Losartan is a promising candidate drug for treatment of GPHYSD due to FBN1 defects. [8] by V Camarena · 2023 — Functional studies in ADAMTSL2-related geleophysic dysplasia provide insights into pathogenesis and potential treatment targets. [12] Losartan treatment had no effect on lysosomal inclusions evaluated by EM ...

Geleophysic dysplasia can be distinguished from other conditions through a careful examination of its characteristic clinical features and the presence or absence of specific symptoms.

Conditions to consider in differential diagnosis:

• Acromicric dysplasia: This condition is characterized by short stature, short extremities, and progressive joint limitation. However, geleophysic dysplasia can be distinguished from acromicric dysplasia by the presence of cardiac abnormalities (e.g., cardiac valvular thickening) [5][9].
• Stiff skin syndrome: This condition is characterized by firm woody induration of the skin with joint contractures. However, geleophysic dysplasia can be distinguished from stiff skin syndrome by its characteristic clinical, histologic, and genetic features [2].
• Progeria: This is a rare genetic disorder that causes premature aging in children. While both conditions involve short stature and joint deformities, progeria is typically characterized by more severe and widespread symptoms, including wrinkled skin and hair loss [2].
• Farber's lipomatosis: This is a rare genetic disorder that affects the development of fat cells. While both conditions involve thickened skin and joint deformities, Farber's lipomatosis is typically characterized by the presence of lipomas (benign tumors composed of fat tissue) [2].

Key features to consider:

• Cardiac abnormalities: Geleophysic dysplasia is often associated with cardiac valvular disease, which can be a distinguishing feature from other conditions.
• Short stature and extremities: Both geleophysic dysplasia and acromicric dysplasia are characterized by short stature and short extremities. However, the presence of cardiac abnormalities in geleophysic dysplasia can help distinguish it from acromicric dysplasia [5][9].
• Progressive joint limitation and contractures: Both conditions involve progressive joint limitation and contractures. However, geleophysic dysplasia is often associated with more severe and widespread symptoms.

References:

[2] Bernard A. Cohen, in Neonatal Dermatology (Second Edition), 2008 [5] Overlapping w/geleophysic dysplasia Distinguishing from geleophysic dysplasia; ADAMTS10 ADAMTS17 FBN1 LTBP2: Weill-Marchesani syndrome: AD AR 1: See Table 2. See Table 2. ADAMTSL2: Dysplastic cortical hyperostosis, Al-Gazali type: AR: FBN1 LTBP3: Acromicric dysplasia: AD: SMAD4: Myhre syndrome: AD [9] Geleophysic dysplasia (GD) and acromicric dysplasia (AD) are characterized by short stature, short extremities, and progressive joint limitation. ... Differential diagnosis. Acromelic dysplasia