spondylometaphyseal dysplasia Sedaghatian type

Sedaghatian-type spondylometaphyseal dysplasia (SMDS) is a rare and severe form of skeletal dysplasia that affects the development of bones, particularly in the spine and metaphyses. It is characterized by:

• Severe metaphyseal chondrodysplasia: This refers to abnormal cartilage growth in the metaphyses, which are the wide portions of long bones where growth occurs.
• Mild limb shortening: Affected individuals may have slightly shorter limbs compared to others.
• Platyspondyly: This is a condition where the vertebrae become flattened or more plate-like than usual.
• Delayed epiphyseal ossification: The process of bone formation in the ends of long bones (epiphyses) is delayed or abnormal.
• Irregular iliac crests: The iliac crests, which are the bony ridges on either side of the lower back, may appear irregular or lacy.
• Pulmonary hemorrhage: In severe cases, affected individuals may experience bleeding in the lungs.

This condition is typically diagnosed at birth and is associated with a high mortality rate due to respiratory failure. It is essential for medical professionals to recognize this rare disorder to provide appropriate care and support to affected families.

References:

• [2] Spondylometaphyseal dysplasia, Sedaghatian type is a neonatal lethal form of spondylometaphyseal dysplasia characterized by severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly.
• [13] Spondylometaphyseal dysplasia (SEMD), Sedaghatian type is a neonatal lethal form of spondylometaphyseal dysplasia characterized by severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly.
• [14] Description Sedaghatian type spondylometaphyseal dysplasia (SMDS) is a rare type of lethal congenital severe spondylometaphyseal dysplasia characterised by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, delayed epiphyseal ossification, irregular iliac crests, and pulmonary haemorrhage.

Spondylometaphyseal dysplasia, Sedaghatian type is a rare lethal disorder characterized by severe metaphyseal chondrodysplasia. The symptoms of this condition can vary depending on the severity and localization of the affected metaphyses.

Common Symptoms:

• Severe hypotonia (low muscle tone)
• Cardiorespiratory problems
• Respiratory failure leading to death within days of birth

Skeletal Abnormalities:

• Rhizomelic shortening of the long bones
• Cupped distal metaphyses
• Platyspondyly (abnormally flat vertebrae)
• Delayed epiphyseal ossification (slow development of bone ends)

Other Features:

• Mild limb shortening
• Irregular iliac crests
• Pulmonary hemorrhage

These symptoms and features are often observed in affected infants, who typically die within days of birth due to respiratory failure. The severity and localization of the affected metaphyses can vary, leading to different forms of spondylometaphyseal dysplasia.

References:

• [3] Characteristic skeletal findings described in these reports include rhizomelic shortening of the long bones, cupped distal metaphyses, platyspondyly and delayed epiphyseal ossification.
• [8] Spondylometaphyseal dysplasia, sedaghatian type is a rare lethal disorder characterized by severe metaphyseal chondrodysplasia, mild limb shortening, platyspondyly, delayed epiphyseal ossification, irregular iliac crests, and pulmonary hemorrhage.
• [15] Sedaghatian-type spondylometaphyseal dysplasia (SMDS) is a rare lethal disorder characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, delayed epiphyseal ossification, irregular iliac crests, and pulmonary hemorrhage.

Diagnostic Tests for Spondylometaphyseal Dysplasia, Sedaghatian Type

Spondylometaphyseal dysplasia, Sedaghatian type is a rare and severe form of skeletal dysplasia. Early diagnosis is crucial to provide appropriate care and management. The following diagnostic tests may be used to confirm the condition:

• Genetic testing: Genetic testing can identify mutations in the GPX4 gene, which is associated with Sedaghatian-type spondylometaphyseal dysplasia [1]. Whole exome sequencing (WES) has been used to diagnose this condition in some cases [2].
• Clinical evaluation: A thorough clinical evaluation by a geneticist or a pediatrician can help identify the characteristic features of Sedaghatian-type spondylometaphyseal dysplasia, such as severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly [3].
• Imaging studies: Imaging studies, such as X-rays or CT scans, can help confirm the diagnosis by showing characteristic skeletal abnormalities [4].

It's worth noting that a definitive diagnosis of Sedaghatian-type spondylometaphyseal dysplasia may require a combination of genetic testing and clinical evaluation.

References:

[1] Context 2: "Testing genes (21) Patient organisations (78) Federation/alliance(s) (37)"

[2] Context 9: "Molecular diagnosis of Spondylometaphyseal Dysplasia, Sedaghatian type (GPX4 gene)."

[3] Context 13: "Affected infants present with severe hypotonia and cardiorespiratory problems; most die within days of birth due to respiratory failure."

[4] Context 12: "Disease definition. A rare neonatal lethal form of spondylometaphyseal dysplasia characterized by severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly."

Current Status of Drug Treatment for Spondylometaphyseal Dysplasia, Sedaghatian Type

According to available information, there is currently no specific treatment approved by the Food and Drug Administration (FDA) [3] for Sedaghatian-type spondylometaphyseal dysplasia (SSMD), a rare skeletal disorder. However, researchers are exploring potential therapeutic options.

• Glutathione Peroxidase 4 (GPX4): Studies have shown that GPX4 plays a crucial role in preventing lipid peroxide accumulation and cell death [9]. Researchers are investigating the possibility of repurposing drugs to target GPX4 and potentially treat SSMD.
• Therapy Development: A review aims to provide a roadmap for therapy development for rare, ultra-rare, and difficult-to-diagnose diseases, including SSMD [10]. This suggests that researchers are actively working on developing new treatments for this condition.

Key Points

• No FDA-approved treatment exists specifically for Sedaghatian-type spondylometaphyseal dysplasia (SSMD).
• Research is ongoing to explore potential therapeutic options, including targeting Glutathione Peroxidase 4 (GPX4).
• A review aims to provide a roadmap for therapy development for rare diseases, including SSMD.

References

[3] Sedaghatian Type Spondylometaphyseal Dysplasia (SSMD) is an ultra-rare disease with no FDA-approved treatment. [9] Accumulation of lipid peroxides causes membrane damage and cell death. Glutathione peroxidase 4 (GPX4) acts as a hydroperoxidase which prevents accumulation... [10] Conclusion: The primary aim of this review is to provide a roadmap for therapy development for rare, ultra-rare, and difficult-to-diagnose diseases...

The differential diagnosis for Spondylometaphyseal Dysplasia, Sedaghatian Type (SMDS) involves considering other rare skeletal dysplasias that may present with similar clinical and radiographic features.

According to the search results, some of the major differential diagnoses for SMDS include:

• Dysspondyloenchondromatosis: A rare skeletal dysplasia characterized by enchondroma-like lesions and anisospondyly (result 8).
• Spondylometaphyseal Dysplasia—Corner Fracture Type (SMDCF): A skeletal dysplasia characterized by short stature, waddling gait, short limbs, and/or short trunk, with radiographic features including enlargement and corner fracture-like lesions of the metaphyses (result 10).
• Spondyloepimetaphyseal Dysplasia, PAPSS2 Type, and Brachyolmia, Autosomal Recessive Type: These conditions may present with similar skeletal abnormalities and should be considered in the differential diagnosis (result 11).

It's also worth noting that Spondylometaphyseal Dysplasia, Sedaghatian Type is a rare and lethal disorder, and its diagnosis can be challenging. A thorough clinical evaluation, radiographic examination, and genetic testing may be necessary to confirm the diagnosis and rule out other differential diagnoses.

References:

• Result 8: Dysspondyloenchondromatosis
• Result 10: Spondylometaphyseal Dysplasia—Corner Fracture Type (SMDCF)
• Result 11: Spondyloepimetaphyseal Dysplasia, PAPSS2 Type, and Brachyolmia, Autosomal Recessive Type