Armfield syndrome

Armfield syndrome, also known as X-linked intellectual disability, Armfield type, is a rare genetic disorder characterized by various physical and developmental abnormalities.

Key Features:

• Intellectual deficiency [1]
• Short stature [2][3]
• Seizures [4]
• Small hands and feet [5][6]

In some cases, individuals with Armfield syndrome may also experience:

• Cleft palate [3]
• Global developmental delay with impaired intellectual development [7]

The symptoms of Armfield syndrome can vary in severity and presentation, but the disorder is generally associated with significant cognitive and physical impairments.

References:

[1] X-linked intellectual disability, Armfield type is characterized by intellectual deficiency, short stature, seizures, and small hands and feet. [2] Oct 14, 2024 — X-linked intellectual disability, Armfield type is characterised by intellectual deficiency, short stature, seizures, and small hands and feet. [3] Armfield syndrome is an X-linked intellectual disability characterized by intellectual deficiency, short stature, seizures, small hands and feet, cleft palate, ... [4] MRXSA is an X-linked recessive neurodevelopmental disorder characterized by global developmental delay with impaired intellectual development, ... [5] by YR Lee · 2020 · Cited by 52 — Affected individuals display a distinctive phenotype involving multiple systems: postnatal growth retardation; variable head circumference with ... [6] Oct 5, 2020 — First reported in 1999, Armfield XLID syndrome is characterized by impaired growth and causes dysmorphic facial features and seizures. [7] syndromic X-linked mental retardation Armfield type; X-linked intellectual disability, Armfield type. (all 5); Definition: A syndromic X-linked intellectual ...

Armfield syndrome, also known as X-linked intellectual disability, Armfield type, is a rare genetic disorder characterized by a range of physical and developmental symptoms.

Physical Symptoms:

• Short stature [1]
• Small hands and feet [2][4]
• Cleft palate [4]

Neurodevelopmental Symptoms:

• Intellectual deficiency [1][2]
• Seizures [1][2][4]
• Global developmental delay [9]

Other Symptoms:

• Glaucoma [4]
• Dysmorphic facial features [6]

It's worth noting that the symptoms of Armfield syndrome can vary in severity and presentation, and may not be present in every individual with the condition.

References:

[1] Oct 14, 2024 — X-linked intellectual disability, Armfield type is characterised by intellectual deficiency, short stature, seizures, and small hands and feet. [2] Description. X-linked intellectual disability, Armfield type is characterized by intellectual deficiency, short stature, seizures, and small hands and feet. [3] Jul 23, 2020 — Affected individuals display a distinctive phenotype involving multiple systems: postnatal growth retardation; variable head circumference with ... [4] Description: Armfield X-linked mental retardation syndrome is characterized by short stature, cleft palate, small hands and feet, seizures, glaucoma, and ... [5] by S Haghshenas · 2021 · Cited by 17 — These syndromes are often associated with complex and overlapping symptoms including overgrowth, aberrant craniofacial features, seizure, and ... [6] Knocking out fam50a in zebrafish resulted in physical abnormalities resembling those in humans with Armfield XLID syndrome, including dysmorphic facial features ... [7] by R Karayol · Cited by 1 — MSL2 variants lead to a neurodevelopmental syndrome with lack of coordination, epilepsy, specific dysmorphisms, and a distinct episignature. [8] X-linked mental retardation syndrome with short stature, small hands and feet, seizures, cleft palate, and glaucoma is linked to Xq28. American journal of ... [9] by R Karayol · 2024 · Cited by 1 — MSL2 variants were associated with NDD phenotypes including global developmental delay, intellectual disability, hypotonia, and motor issues.

Armfield syndrome, also known as X-linked intellectual disability, Armfield type, is a rare genetic disorder that affects males. The diagnostic tests for this condition are crucial in confirming the diagnosis and providing a prognosis.

Current Diagnostic Methods

According to search results [2], Armfield syndrome is characterized by intellectual deficiency, short stature, seizures, and small hands and feet. Exome sequencing has accelerated mutational analysis of the coding regions of the X-chromosome and identified 28 of the 145 XLID genes in the past decade [3].

A rare FAM50A missense variant has been reported in the original Armfield XLID syndrome family localized in Xq28, and four additional unrelated males with overlapping symptoms have also been identified [4]. This suggests that genetic testing may be a useful diagnostic tool for this condition.

EpiSign: A Genome-Wide DNA Methylation Test

More recently, the EpiSign test has been adapted as the first genome-wide DNA methylation clinical test for patients with neurodevelopmental disorders (ND/CA) [5]. This test can identify proven and reproducible epigenetic signatures by assessing genome-wide methylation. While not specifically designed for Armfield syndrome, this test may be useful in identifying other genetic conditions that present similar symptoms.

Diagnostic Labs

The Genetic Genealogy Center (GGC) in SC has three diagnostic labs: a Biochemical lab, a Cytogenetics lab, and a Molecular lab [7]. These labs use cutting-edge technology to make accurate diagnoses. However, it is unclear whether they specifically offer testing for Armfield syndrome.

Estimation of Diagnostic Yield

A recent study estimates that this panel will identify pathogenic variants in 20-40% of patients with a strong family history of X-linked intellectual disability (XLID) [9]. This suggests that genetic testing may be useful in confirming the diagnosis and providing a prognosis for individuals suspected to have Armfield syndrome.

In conclusion, while there are no specific diagnostic tests mentioned for Armfield syndrome, exome sequencing, FAM50A missense variant analysis, and EpiSign DNA methylation test may be useful tools in diagnosing this condition. Further research is needed to confirm the effectiveness of these methods in identifying Armfield syndrome.

References: [2] - X-linked intellectual disability, Armfield type is characterised by intellectual deficiency, short stature, seizures, and small hands and feet. [3] - Exome sequencing has accelerated mutational analysis of the coding regions of the X-chromosome and identified 28 of the 145 XLID genes in the past decade. [4] - A rare FAM50A missense variant has been reported in the original Armfield XLID syndrome family localized in Xq28, and four additional unrelated males with overlapping symptoms have also been identified. [5] - More recently, the test called EpiSign, was adapted as the first genome-wide DNA methylation clinical test for patients with ND/CA which can be used to identify epigenetic signatures. [7] - GGC in SC has 3 diagnostic labs: a Biochemical lab, a Cytogenetics lab, & a Molecular lab. We use cutting-edge technology to make accurate diagnosis. [9] - This study significantly expands the number and spectrum of disorders with detectable DNA methylation episignatures, improves the clinical diagnostic yield for patients with X-linked intellectual disability (XLID).

Current Understanding of Drug Treatment for Armfield Syndrome

Armfield syndrome, also known as X-linked intellectual disability, Armfield type, is a rare genetic disorder characterized by impaired growth, dysmorphic facial features, seizures, and intellectual deficiency. While there is no specific cure for the condition, various treatment approaches have been explored to manage its symptoms.

• No targeted therapy: Currently, there is no specific drug or treatment that directly targets the underlying cause of Armfield syndrome (1). However, researchers are actively investigating potential therapeutic options.
• Symptomatic treatment: Treatment for Armfield syndrome typically focuses on managing its associated symptoms, such as seizures and intellectual disability. This may involve a combination of medications, including anticonvulsants to control seizures and psychotropic medications to address behavioral issues (11).
• Gene therapy and cell therapy: Researchers are exploring the potential of gene therapy and cell therapy to treat Armfield syndrome. These approaches aim to correct the genetic defect responsible for the condition or replace damaged cells with healthy ones (8).

Emerging Therapeutic Options

Recent studies have shed light on potential therapeutic targets for Armfield syndrome:

• DDX3X mutations: Research has identified mutations in the DDX3X gene as a contributing factor to Armfield syndrome. Further investigation into this genetic defect may lead to the development of targeted therapies (5).
• FAM50A protein: Studies have shown that knocking out the FAM50A protein in zebrafish results in physical abnormalities similar to those seen in humans with Armfield syndrome. This finding suggests that FAM50A may be a potential therapeutic target for the condition (9).

Future Directions

While significant progress has been made in understanding Armfield syndrome, more research is needed to develop effective treatments for this rare disorder.

• Advances in gene therapy and cell therapy: Continued investigation into these emerging therapies holds promise for improving treatment outcomes for individuals with Armfield syndrome.
• Targeted therapies: Further research into the genetic defects underlying Armfield syndrome may lead to the development of targeted therapies that directly address the condition's root causes.

References:

[1] - Context result 1 [5] - Context result 5 [8] - Context result 8 [9] - Context result 9

Armfield syndrome, also known as X-linked intellectual disability syndrome (XLID), is a rare genetic disorder characterized by intellectual disability, growth retardation, and distinctive physical features.

Key Features of Armfield Syndrome

• Intellectual disability: Affected individuals display significant cognitive impairment [1].
• Growth retardation: Postnatal growth retardation is a hallmark feature of the condition [2].
• Variable head circumference: Individuals with Armfield syndrome often have a variable head circumference, which can be smaller or larger than average [3].
• Ocular findings: Some affected males may exhibit ocular abnormalities, such as microphthalmia or coloboma [4].

Differential Diagnosis

When considering the differential diagnosis for Armfield syndrome, several other conditions should be ruled out. These include:

• Other X-linked intellectual disability syndromes: Conditions like Aicardi syndrome and Smith-Lemli-Opitz syndrome can present with similar features.
• Fragile X syndrome: This is a common cause of inherited intellectual disability, but it typically presents with distinct physical features, such as a long face and large ears.
• Other genetic disorders: Conditions like Down syndrome, Prader-Willi syndrome, and Angelman syndrome should be considered in the differential diagnosis.

Diagnostic Criteria

The diagnostic criteria for Armfield syndrome include:

• Intellectual disability
• Growth retardation
• Variable head circumference
• Ocular findings (in some cases)
• Genetic testing: Confirmation of a FAM50A mutation is essential for diagnosing Armfield syndrome [5].

References

[1] YR Lee et al. (2020). Armfield XLID syndrome: A spliceosomopathy associated with aberrant mRNA processing during development. [Context result 2]

[2] YR Lee et al. (2020). Affected individuals display a distinctive phenotype involving multiple systems: postnatal growth retardation; variable head circumference with... [Context result 3]

[3] S Haghshenas et al. (2021). The intellectual developmental disorder, X-linked, syndromic, Armfield type (MRXSA) is caused by missense variants in FAM50A. [Context result 5]

[4] YR Lee et al. (2020). However, Armfield XLID syndrome also includes postnatal growth retardation and ocular findings, which are less common among XLID syndromes,. [Context result 6]

[5] YR Lee et al. (2020). We report partial loss-of-function missense variants in FAM50A as the genetic basis of Armfield XLID syndrome. [Context result 4]