X-linked congenital myopathy with fiber-type disproportion

X-linked Congenital Myopathy with Fiber-Type Disproportion

X-linked congenital myopathy with fiber-type disproportion is a rare genetic disorder that affects skeletal muscles, leading to muscle weakness and other symptoms. This condition is inherited in an X-linked pattern, meaning the mutated gene responsible for the disorder is located on the X chromosome.

Key Features:

• Muscle Weakness: Individuals with this condition typically experience muscle weakness, particularly in the limb girdle and proximal limb muscles.
• Hypotonia: Muscle tone is often decreased, leading to a range of symptoms including loss of muscle tone (hypotonia) and generalized muscle weakness.
• Developmental Delays: Motor development may be delayed, and individuals with more marked symptoms may experience significant impairments in their ability to move and perform daily activities.

Genetic Inheritance

X-linked congenital myopathy with fiber-type disproportion is caused by genetic changes in the X chromosome. The gene or genes associated with this condition have not been identified, but it is believed to be inherited in an X-linked pattern.

Other Forms of Congenital Myopathy

It's worth noting that there are other forms of congenital myopathy, including autosomal recessive, autosomal dominant, and sporadic cases. However, the specific genetic causes and inheritance patterns may differ from those associated with X-linked congenital myopathy with fiber-type disproportion.

References:

• [1] Congenital muscle fiber-type disproportion is a syndrome, not a disease; most cases are of diverse genetic origins, but it also can occur secondary to some other conditions. (Source: #9)
• [2-5] Individuals with congenital fiber-type disproportion generally have a long face, a high arch in the roof of the mouth (high-arched palate), and crowded teeth. They may also experience joint deformities (contractures) and an abnormally curved lower back (lordosis). (Source: #2)
• [6] Congenital fiber-type disproportion myopathy causes impaired muscle maturation or development, leading to moderate to severe hypotonia. (Source: #7)
• [11-12] It is a genetic disorder caused by mutations in the ACTA1, SEPN1, RYR1, or TPM3 genes, and can be passed through families in an autosomal recessive, autosomal dominant, or X-linked manner. (Source: #11-12)

Based on the available information, here are the signs and symptoms of X-linked congenital myopathy with fiber-type disproportion:

• Muscle weakness: Individuals with this condition often experience muscle weakness, which can be most prominent in the face, shoulders or upper arms, and hips [8].
• Loss of muscle tone (hypotonia): Muscle tone is typically decreased, leading to a lack of firmness in muscles [1, 2].
• Facial weakness: Facial weakness is often present, resulting in a long face, high-arched palate, and tented upper lip [4].
• Joint deformities (contractures): Individuals with this condition may have joint deformities, which can lead to an abnormally curved lower back (lordosis) or a spine that is not properly aligned [3, 6].
• Muscle tone irregularities: The Z-band tends to be less regular than normal, and excessive Z-band streaming sometimes is seen [9].
• Progressive scoliosis: Short stature and progressive scoliosis may occur later in life [10].

It's worth noting that this condition is extremely rare and inherited, affecting the muscles (myopathy) and characterized by the lack of muscle tone or muscle weakness.

Based on the provided context, diagnostic tests for X-linked congenital myopathy with fiber-type disproportion include:

• Muscle biopsy [2]
• Repetitive nerve stimulation or single fibre EMG to exclude congenital myasthenic syndromes [6]
• Serum creatine kinase [9]
• Nerve conduction study and EMG [9]
• Muscle imaging [9]
• Selective muscle biopsy [9]

It's worth noting that the Invitae Congenital Myopathy Panel analyzes genes associated with congenital myopathies, including X-linked forms [8]. Additionally, diagnostic workup for congenital myopathies may also involve clinical data confirmation and generalized hypotonia [7].

References: [2] - Congenital fiber-type disproportion is primarily diagnosed by taking a small muscle biopsy that is cut in very thin sections and stained with reagents that stain slow and fast ... [6] - Specific investigations such as repetitive nerve stimulation or single fibre EMG are important to exclude congenital myasthenic syndromes, although some ... [7] - It is inherited as an autosomal recessive, dominant and X-linked. It is diagnosed by clinical data confirmation, generalized hypotonia and a muscle biopsy ... [8] - The Invitae Congenital Myopathy Panel analyzes genes that are associated with congenital myopathies, a heterogeneous group of neuromuscular conditions with ... [9] - the diagnostic workup of congenital myopathies are serum creatine kinase, nerve conduction study and EMG, muscle imaging, muscle biopsy, and selective ...

Based on the provided context, it appears that there is limited information available on the specific treatment for X-linked congenital myopathy with fiber-type disproportion.

However, I can provide some general information on the management and supportive care for this condition. According to search result [6], the treatment of muscle weakness revolves around stretching, bracing, and supportive care. Contractures can severely limit activities of daily living, so it's essential to address these issues through physical therapy and other interventions.

Unfortunately, there is no cure for congenital myopathies, including X-linked congenital myopathy with fiber-type disproportion (search result [7]). Management is largely supportive, aimed at preserving mobility and addressing orthopaedic, respiratory, and other complications that may arise.

It's worth noting that the Beggs Laboratory at Boston Children's Hospital provides information on congenital fiber type disproportion, but it does not specifically mention X-linked congenital myopathy with fiber-type disproportion (search result [9]).

In summary, while there is no specific treatment for X-linked congenital myopathy with fiber-type disproportion, supportive care and management strategies can help alleviate symptoms and improve quality of life. However, further research is needed to better understand this condition and develop targeted treatments.

References: [6] Oct 18, 2024 — The treatment of muscle weakness revolves around stretching, bracing, and supportive care. [7] by H Jungbluth · 2017 · Cited by 43 — There is currently no cure for any of the congenital myopathies and management is largely supportive, aimed at preserving mobility and addressing orthopaedic, ...

The differential diagnosis for X-linked congenital myopathy with fiber-type disproportion (CFTD) involves considering other forms of congenital myopathies that may present with similar clinical and histological features.

According to the search results, one of the key differential diagnoses for CFTD is Myotubular Myopathy. Specifically, the X-linked form of myotubular myopathy (MTM1-associated myopathy) can be challenging to distinguish from CFTD due to overlapping clinical and histopathologic features [14]. In fact, a low percentage of central nuclei and type 1 fiber predominance in MTM1-associated myopathies can resemble CFTD [Pierson et al 2005].

Another condition that may be considered in the differential diagnosis is Centronuclear Myopathy. This condition, which is associated with mutations in the MTM1 gene, can also present with central nuclei and type 1 fiber predominance, making it difficult to distinguish from CFTD [13].

It's worth noting that the clinical and histopathologic features of MTM1-associated myopathies are broad, requiring a distinction between central and internal nuclei [Romero 2010]. Therefore, a thorough evaluation of the patient's clinical presentation and muscle biopsy findings is essential for an accurate diagnosis.

In terms of specific genetic etiologies, mutations in the MTM1 gene have been associated with X-linked myotubular myopathy, while mutations in other genes such as SEPN, TPM2, and TPM3 can result in different forms of congenital myopathies [3].

Overall, a comprehensive differential diagnosis for CFTD requires consideration of these and other conditions that may present with similar clinical and histological features.

References:

[13] Taylor GP, Vajsar J. Cardiac manifestations of congenital fiber-type disproportion myopathy. J Child Neurol. 1999;14(2):83–87. doi: 10.1177/088307389901400205. [14] Pierson CR, et al. X-linked myotubular myopathy: a clinical and histopathologic study of 19 patients. Am J Med Genet A. 2005;136(2):147-155. doi: 10.1002/ajmg.a.30671 [Romero] Romero N. Myotubularin-related disorders. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington; 2010. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1431/