Dyggve-Melchior-Clausen disease

Dyggve-Melchior-Clausen Disease Overview

Dyggve-Melchior-Clausen disease (DMC) is a rare, progressive genetic disorder characterized by abnormal skeletal development, microcephaly, and intellectual disability. The condition was first reported in 1962 in three siblings where the father was the mother's paternal uncle.

Key Features:

• Progressive spondyloepimetaphyseal dysplasia: Abnormalities of the growth plates, including platyspondyly with notched end plates and metaphyseal irregularities.
• Short-trunk dwarfism: Shortened trunk with a barrel-shaped chest.
• Microcephaly: Small head size.
• Intellectual disability: Varying degrees of mental retardation.
• Coarse facies: Distinct facial features.

Clinical Description:

DMC is characterized by progressive dwarfism, short trunk, protruding sternum, rhizomelic limb shortening, postnatal microcephaly with facial dysmorphism, coarse face, and intellectual disability varying from moderate to severe. Physical measurements at birth are typically within normal limits, but growth retardation becomes apparent later in life.

Genetic Basis:

DMC is an autosomal recessive disorder caused by genetic mutations, also known as pathogenic variants. These mutations can be hereditary or occur randomly when cells divide.

References:

• [1] Dyggve, Melchior, and Clausen's original report in 1962.
• [3-4, 12] Descriptions of DMC's clinical features and radiologic appearances.
• [5, 9] Cited studies on the association of progressive spondyloepimetaphyseal dysplasia with microcephaly and intellectual disability.
• [10, 15] Descriptions of DMC's genetic basis and clinical characteristics.

Dyggve-Melchior-Clausen Syndrome (DMC) Signs and Symptoms

Dyggve-Melchior-Clausen syndrome is a rare genetic disorder characterized by several distinct signs and symptoms. Some of the key features include:

• Abnormal skeletal development: This can manifest as abnormal head or neck shape, coarse facial features, brachydactyly (short fingers), and malalignment of the spine with kyphoscoliosis.
• Microcephaly: DMC is often associated with microcephaly, which refers to a smaller-than-average head size.
• Intellectual disability: Individuals with DMC may experience intellectual disability or mental retardation.
• Coarse facial features: The face may appear coarse or rough in texture.
• Abnormality of limbs: Brachydactyly and other limb abnormalities are common.
• Abdominal issues: Abnormalities of the digestive system, such as feeding difficulties, can occur.
• Spinal cord compression: In some cases, atlantoaxial instability can lead to spinal cord compression, weakness, and paralysis.

These symptoms often become apparent in early childhood. The chest may appear barrel-shaped, and there may be malalignment of the spine with kyphoscoliosis. The hands and feet are often broad, and the fingers might be clawed.

Radiological signs: Specific radiologic signs include generalized platyspondyly (flattening of the vertebrae) with double-humped end plates and a lace-like appearance of thickened iliac crests.

These symptoms can vary in severity and may not be present in all individuals with DMC. Early diagnosis is crucial for providing proper care and management.

References:

• [1] Dyggve-Melchior-Clausen syndrome (DMC) is a rare, progressive genetic disorder characterized by abnormal skeletal development, microcephaly and intellectual ...
• [2] It is characterized by the association of progressive spondyloepimetaphyseal dysplasia (SEMD), microcephaly, mental retardation (MR), and coarse facies.
• [3] Mar 13, 2012 — In 11% of patients, there is atlantoaxial (upper neck vertebrae) instability that can lead to spinal cord compression, weakness and paralysis.
• [4] Clinical features · Abnormality of head or neck. Coarse facial features · Abnormality of limbs. Brachydactyly · Abnormality of the digestive system. Abdominal ...
• [5] The chest is barrel shaped, and malalignment of the spine with kyphoscoliosis is common. The hands and feet are broad, and the fingers might be clawed.
• [6] by S Schorr · 1977 · Cited by 30 — The radiologic signs of generalized platy- spondyly with double humped end plates and the lace- like appearance of thickened iliac crests are patho- gnomonic.
• [7] The chest is barrel shaped, and malalignment of the spine with kyphoscoliosis is common. The hands and feet are broad, and the fingers might be clawed.
• [8] by S Schorr · 1977 · Cited by 30 — The radiologic signs of generalized platy- spondyly with double humped end plates and the lace- like appearance of thickened iliac crests are patho- gnomonic.
• [9] Chest deformities, feeding difficulties, and developmental delay usually occur before 18 months. Disproportionate short stature usually occurs after 18 months.

Dyggve-Melchior-Clausen disease (DMC) is a rare genetic disorder, and diagnostic tests are essential for its confirmation. Based on the search results, here's an overview of the diagnostic tests associated with DMC:

• Genetic analysis: This is the primary method for diagnosing DMC. Genetic testing can identify the pathogenic variants responsible for the condition (see [12]). Molecular genetic testing, such as next-generation sequencing, can confirm the diagnosis (see [6] and [9]).
• Blood count, blood glucose, urine analysis, and serum calcium, phosphorus, and alkaline phosphatase tests: These laboratory tests are normal in all cases of DMC (see [3]). Therefore, they are not useful for diagnosing this condition.
• Imaging studies: While there is no specific mention of imaging studies in the search results, radiological features such as platyspondyly with double vertebral humps, irregularly ossified femoral heads, and lacy pelvis iliac crests may be observed (see [8]). However, these findings are not diagnostic on their own.

It's essential to note that a diagnosis of DMC is typically made through genetic analysis. A healthcare professional or a genetic counselor can help determine the best course of action for testing and diagnosis.

References:

[3] MS Aglan · 2009 · Cited by 22 — Other laboratory tests, including blood count, blood glucose, urine analysis, and serum calcium, phosphorus, and alkaline phosphatase were normal in all cases. [6] Confirmation of the diagnosis was done by next generation sequencing-based molecular genetic testing, as the mother had an ongoing pregnancy and prenatal ... [8] Radiological features include platyspondyly with double vertebral humps, irregularly ossified femoral heads, and lacy pelvis iliac crests. Skeletal ... [12] Dyggve-Melchior-Clausen disease is caused by genetic mutations, also known as pathogenic variants. ...

Current Drug Treatments for Dyggve-Melchior-Clausen Disease

Dyggve-Melchior-Clausen disease (DMC) is a rare skeletal disorder that requires multidisciplinary management. While there are no targeted molecular therapies specifically designed for DMC, various treatments can help alleviate symptoms and improve quality of life.

• Recombinant Growth Hormone (rGH) Therapy: Studies suggest that rGH therapy may be employed to improve stature based on the underlying etiology and growth velocity [4][6]. This treatment aims to address the short-trunked dwarfism characteristic of DMC.
• Multidisciplinary Approach: Management of DMC typically involves a team of healthcare professionals, including orthopedic specialists, endocrinologists, and geneticists. A comprehensive approach is essential to address the specific symptoms and complications associated with this condition [10].

Limitations and Future Directions

While these treatments can provide some relief, it's essential to note that there are currently no targeted molecular therapies for DMC syndrome [9]. Ongoing research aims to better understand the underlying causes of this disease and develop more effective treatment options.

References:

• [4] Upadhyay R. (2022) - Recombinant growth hormone (rGH) therapy may be employed to improve stature based on the underlying etiology and growth velocity.
• [6] Upadhyay R. (2022) - Skeletal abnormalities associated with DMC can be addressed through rGH therapy.
• [9] López-Garrido MP, et al. (2022) - Currently, there are no targeted molecular therapies for DMC syndrome.
• [10] Chavan S. (2024) - Management of DMC typically involves a multidisciplinary approach aimed at addressing specific symptoms and complications.

Differential Diagnosis of Dyggve-Melchior-Clausen Disease

Dyggve-Melchior-Clausen disease (DMC) is a rare genetic disorder characterized by progressive skeletal development, microcephaly, and intellectual disability. When diagnosing DMC, it's essential to consider differential diagnoses that may present similar clinical and radiological features.

Similar Conditions:

• Morquio's Syndrome: This autosomal recessive skeletal dysplasia can be initially mistaken for DMC due to similarities in clinical and radiological findings.
• Smith-McCort Syndrome: A rare genetic disorder characterized by progressive dwarfism, short trunk, protruding sternum, rhizomelic limb shortening, postnatal microcephaly with facial dysmorphism, coarse face, and intellectual disability.

Key Diagnostic Features:

To differentiate DMC from these conditions, clinicians should focus on the following key features:

• Progressive Spondyloepimetaphyseal Dysplasia: A distinctive radiological feature of DMC.
• Microcephaly: A characteristic feature of DMC, often accompanied by intellectual disability.
• Coarse Facies: A common finding in DMC patients.

Genetic Mutations:

DMC is caused by genetic mutations, also known as pathogenic variants. These mutations can be hereditary or occur randomly during cell division. Understanding the genetic basis of DMC is crucial for accurate diagnosis and management.

Clinical Considerations:

When considering differential diagnoses for DMC, clinicians should take into account the patient's clinical presentation, radiological findings, and family history. A comprehensive evaluation by a multidisciplinary team, including geneticists, radiologists, and pediatricians, is essential for an accurate diagnosis.

References:

• [1] Dyggve-Melchior-Clausen syndrome (DMC) is a rare autosomal recessive spondyloepimetaphyseal dysplasia caused by pathogenic variants. [Source: 7]
• The diagnosis of Dyggve-Melchior-Clausen syndrome is based on clinical and radiological findings. Prenatal diagnosis can be offered for the parents who had a previous child with DMC. [Source: 8]