frontometaphyseal dysplasia 1

Frontometaphyseal dysplasia (FMD) type 1, also known as FMD1, is a genetic disorder that affects skeletal development and other organs in the body.

Characteristics:

• Skeletal abnormalities: FMD1 is characterized by anomalies in ossification and skeletal patterning of the axial and appendicular skeleton [5].
• Facial dysmorphism: Individuals with FMD1 often have unique facial features, which can include a range of anomalies such as supraorbital hyperostosis (excessive bone growth above the eyebrows) [7], cranial hyperostosis (excessive bone growth in the skull), and undermodeling of the small bones [15].
• Digital anomalies: FMD1 is also associated with digital anomalies, which can include flared metaphyses (widening of the ends of long bones) and other abnormalities of the hands and feet.
• Progressive sclerosing skeletal dysplasia: FMD1 is a progressive condition that leads to a sclerosing (hardening) of the skeleton over time [7].

Genetic basis:

• FLNA gene mutations: FMD1 is caused by mutations in the FLNA gene, which is responsible for encoding filamin A, a protein involved in various cellular processes including skeletal development [5].
• X-linked inheritance: FMD1 is inherited in an X-linked manner, meaning that it is more commonly found in males than females due to the presence of two X chromosomes in females [10].

Clinical presentation:

• Congenital disorder: FMD1 is a congenital condition, meaning that it is present at birth.
• Variable severity: The severity of FMD1 can vary widely among affected individuals, with some experiencing mild symptoms while others have more severe manifestations.

Overall, frontometaphyseal dysplasia type 1 (FMD1) is a rare genetic disorder characterized by skeletal abnormalities, facial dysmorphism, digital anomalies, and progressive sclerosing skeletal dysplasia.

Frontometaphyseal dysplasia type 1 (FMD1) is a congenital disorder that affects the development of bones and other tissues in the body. The cardinal manifestations in males are skeletal dysplasia, which can include:

• Skull base sclerosis
• Distal phalangeal hypoplasia
• Progressive contractures of the hand over the first two decades resulting in marked limitation of movement at the interphalangeal, metacarpophalangeal joints, wrists, elbows, knees, and ankles

These symptoms can lead to significant limitations in mobility and daily activities. In females, the characteristic facial features may be present without any other symptoms.

In addition to skeletal dysplasia, FMD1 can also cause:

• Mild but progressive contractures of the hands and feet
• Limited movement at the joints
• Hearing loss due to malformations in the tiny bones in the ears (ossicles)
• Abnormalities in the development of other organs and tissues

It's worth noting that the severity and progression of symptoms can vary widely among individuals with FMD1.

Frontometaphyseal dysplasia 1 (FMD1) can be diagnosed through various genetic and clinical tests.

• Genetic analysis: A molecular diagnosis of FMD1 can be provided through targeted mutation analysis, mutation scanning/screening, and sequence analysis of selected exons or the entire coding region [7]. This is recommended for individuals with a personal and/or family history of this disorder to ensure accurate diagnosis.
• 14 tests in the database: There are 14 tests available in the database for FMD1, which can be used to confirm the diagnosis. These tests may include genetic testing, radiographic imaging, and other clinical evaluations [3].
• Gene panel analysis: A 12-gene panel that includes assessment of non-coding variants is ideal for patients with a clinical suspicion of craniometaphyseal dysplasia, which includes FMD1 [9].

It's essential to consult with a healthcare professional or a genetic counselor to determine the most appropriate diagnostic tests for an individual suspected of having FMD1.

References: [3] - There are 14 tests available in the database for this condition. [7] - Genetic analysis to provide a molecular diagnosis of this disorder. [9] - A 12 gene panel that includes assessment of non-coding variants.

Treatment Options for Frontometaphyseal Dysplasia 1

Frontometaphyseal dysplasia 1 (FMD1) is a genetic disorder that affects skeletal development and other organs. While there is no cure for FMD1, various treatment options can help manage its symptoms.

• Hearing Loss Aids: Individuals with FMD1 may experience hearing loss due to the abnormal development of the inner ear. Hearing aids can be an effective way to improve communication and overall quality of life.
• Surgery to Correct Facial Deformities: Surgical interventions can help correct facial deformities, including the frontal deformity associated with FMD1. These procedures aim to restore a more normal appearance and function.
• Surgery to Correct Joint Contractures: Individuals with FMD1 often experience joint contractures, which can lead to limited mobility. Surgery can help correct these issues, improving range of motion and reducing discomfort.
• Scoliosis Correction: Scoliosis is a common feature in individuals with FMD1. Surgical interventions can help correct scoliosis, restoring spinal alignment and reducing the risk of complications.

Other Considerations

While surgery can be an effective treatment option for some symptoms associated with FMD1, it's essential to note that each individual's experience may vary. Treatment plans should be tailored to address specific needs and circumstances.

• Genetic Counseling: Genetic counseling can provide valuable insights into the condition, its inheritance pattern, and potential risks for family members.
• Multidisciplinary Care: A team of healthcare professionals, including geneticists, orthopedic surgeons, and audiologists, can work together to develop a comprehensive treatment plan.

References

[14] The treatment of Frontometaphyseal Dysplasia depends on the symptoms present in the person, and may include: Hearing loss aids for deafness; Surgery to correct the facial deformities including the frontal deformity; Surgery to correct the joint contractures, the limb bowing, and the scoliosis ...

[15] Frontometaphyseal dysplasia-1 (FMD1) is 1 of 4 otopalatodigital syndromes caused by mutations in the FLNA gene. The disorders, which include ...

Frontometaphyseal dysplasia (FMD) has a differential diagnosis with several other rare genetic disorders, including:

• Pyle syndrome: This condition is characterized by abnormalities in skeletal development and problems in other organs of the body. Like FMD, it affects the development of the skeleton and other organs.
• Craniometaphyseal dysplasia (CMD): CMD is a disorder that affects the development of the skull and face bones, leading to abnormalities such as wide nasal bridge, paranasal bossing, and prominent mandible. It also has similarities with FMD in terms of ocular and auditory abnormalities.
• Melnick-Needles syndrome: This is an X-linked disease characterized by generalized skeletal dysplasia, deafness, and urogenital defects. Like FMD, it affects the development of the skeleton and other organs.
• Shprintzen-Goldberg syndrome: This condition is a rare genetic disorder that affects the development of the face and skull bones, leading to abnormalities such as wide nasal bridge and prominent mandible. It also has similarities with FMD in terms of ocular and auditory abnormalities.
• Diaphysary dysplasia (or Kenny-Caffey's syndrome): This is a rare genetic disorder that affects the development of the long bones, leading to abnormalities such as metaphyseal dysplasia.

These conditions are all part of the otopalatodigital spectrum disorders, which also includes otopalatodigital syndrome type 1 and 2. The differential diagnosis for FMD is important for accurate diagnosis and treatment (1, 3, 5, 7, 9).

References: [1] - The differential diagnosis is with Pyle syndrome, craniometaphyseal dysplasia, Melnick-Needles syndrome, Shprintzen-Goldberg syndrome and diaphysary dysplasia (or Kenny-Caffey"s syndrome). [3] - Frontometaphyseal dysplasia is distinguished from the other otopalatodigital spectrum disorders by the presence of joint deformities called contractures that [5] - Frontometaphyseal dysplasia is a disorder involving abnormalities in skeletal development and problems in other organs of the body. [7] - Craniofacial hyperostosis with or without appendicular skeletal involvement in children is not unique to CMD and has a wide differential diagnosis, including frontometadiaphyseal dysplasia, craniodiaphyseal dysplasia and CMDD. [9] - Frontometaphyseal dysplasia (FMD) belongs to the otopalatodigital syndrome spectrum disorder and is characterized by anomalous ossification and skeletal abnormalities.