Legius syndrome

Legius syndrome, also known as NF1-like syndrome, is a rare genetic skin pigmentation disorder characterized by multiple café-au-lait macules with or without axillary or inguinal freckling.

Key Features:

• Multiple café-au-lait spots are a hallmark of Legius syndrome [2][3]
• Freckles in the armpits and groin may occur in some affected individuals [2]
• Unlike neurofibromatosis type 1, there are no tumours found in Legius syndrome [4]

Other Characteristics:

• People with this syndrome may have mild learning and developmental delays [5]
• Legius syndrome is a type of disease called a RASopathy that is caused by mutations (changes) in the SPRED1 gene [5]
• This gene makes a protein involved in a cell signaling pathway that controls many important cell functions [5]

Distinguishing Features:

• Legius syndrome is differentiated from NF1 by the absence of non-pigmentary clinical manifestations seen in this disorder [4]
• It is characterized by multiple café-au-lait macules without neurofibromas or other tumor manifestations of neurofibromatosis type 1 (NF1) [6]

Genetic Basis:

• Legius syndrome is caused by a pathogenic variant in one copy of the SPRED1 gene [8]
• This condition is an autosomal dominant disorder, meaning that only one mutated copy of the gene is needed to cause the condition [14]

Legius syndrome, also known as NF1-like syndrome, is a rare genetic disorder characterized by changes in skin pigmentation and other symptoms.

Common signs and symptoms include:

• Multiple café-au-lait spots on the skin [7]
• Brown spots on the skin
• Freckles in the armpits
• Learning problems [4][5][6]
• Attention problems and hyperactivity [1][3][5][6]
• Being shorter than other children their age [1][3][5][6]

It's worth noting that Legius syndrome is a rare condition, and not all individuals with the disorder will exhibit all of these symptoms. If you or someone you know has been diagnosed with Legius syndrome, it's essential to work with a healthcare professional to develop a personalized treatment plan.

References: [1] What Are the Signs

Diagnostic Tests for Legius Syndrome

Legius syndrome, also known as neurofibromatosis type 1-like disorder or NF1-LIKE, is a rare genetic disorder caused by mutations in the SPRED1 gene. Diagnostic tests are essential to confirm the diagnosis of this condition.

• Genetic Testing: Genetic testing is necessary to confirm the diagnosis of Legius syndrome. This involves sequence analysis of the SPRED1 gene, deletion/duplication analysis, and/or known familial mutation analysis [7][8]. Molecular genetic testing can be used to identify a heterozygous pathogenic variant in SPRED1, which is a key diagnostic criterion for Legius syndrome [10].
• Molecular Genetic Testing: This test involves analyzing the DNA of an individual to detect mutations in the SPRED1 gene. It is essential to confirm the diagnosis and differentiate it from other conditions like neurofibromatosis type 1 (NF1) [12][13].
• Quantitative PCR, Long-range PCR, and Multiplex Ligation-dependent Probe Amplification (MLPA): These techniques may be used in conjunction with genetic testing to detect mutations in the SPRED1 gene [2].

Key Points

• Genetic testing is necessary to confirm the diagnosis of Legius syndrome.
• Molecular genetic testing can identify a heterozygous pathogenic variant in SPRED1, which is a key diagnostic criterion for Legius syndrome.
• Other techniques like quantitative PCR, long-range PCR, and MLPA may be used in conjunction with genetic testing.

References

[2] Oct 14, 2010 — Methods used may include a range of techniques such as quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA) ... [7] Where Legius syndrome is suspected, genetic testing can be used to confirm the diagnosis. This involves: Sequence analysis of SPRED1; Deletion/duplication ... [8] Thus, the diagnosis of Legius syndrome may include molecular testing of the SPRED1 gene, and in some cases the NF1 gene. [10] Diagnosis/testing. The diagnosis of Legius syndrome is established in a proband with suggestive findings and a heterozygous pathogenic variant in SPRED1 identified by molecular genetic testing. ... [12] Thus, the diagnosis of Legius syndrome may include molecular testing of the SPRED1 gene, and in some cases the NF1 gene. [13] Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. ...

Legius syndrome, also known as neurofibromatosis type 1-like disorder or NF1-LIKE, is a rare genetic condition characterized by changes in skin coloring (pigmentation) and the presence of multiple café-au-lait spots. While there are no specific treatments for Legius syndrome, various therapies can help manage its symptoms.

Medications to Manage Symptoms

• There are no medications specifically approved for the treatment of Legius syndrome.
• However, some patients may benefit from medications used to treat other conditions, such as:
  • ADHD: Drug therapy should be considered for the behavioral manifestations of the disorder (ADHD) [2].
  • Pruritus (itching): Diphenhydramine may provide temporary relief for a small subset of patients with pruritus due to cutaneous neurofibromas [6].

Therapeutic Approaches

• Occupational therapy and physical therapy can help improve movement, dexterity, and self-care in individuals with Legius syndrome [7].
• Speech-language therapy may also be beneficial for some patients [7].
• In some cases, medications may be prescribed to manage specific symptoms or complications associated with the condition.

Recent Developments

• Research on MEK inhibitors (MEKi), such as selumetinib and trametinib, has shown promise in treating neurofibromatosis type 1 (NF1) [9].
• However, these medications are not specifically approved for the treatment of Legius syndrome.
• Further research is needed to determine their efficacy and safety in managing symptoms associated with this condition.

References:

[2] Management and treatment. Drug therapy should be considered for the behavioral manifestations of the disorder (ADHD).

[6] For a small subset of patients with pruritus due to cutaneous neurofibromas, diphenhydramine may provide some temporary relief.

[7] How Is Legius Syndrome Treated? · occupational therapy and physical therapy to improve movement, dexterity, and self-care · speech-language therapy · medicines to ...

[9] In recent years, MEK inhibitors (MEKi) such as selumetinib and trametinib have shown great promise.

The differential diagnosis for Legius syndrome includes several conditions that can present with similar symptoms, such as multiple café au lait macules.

• Neurofibromatosis type 1 (NF1): This is a genetic disorder characterized by the growth of non-cancerous tumors on nerve tissue. NF1 and Legius syndrome share some similarities in their clinical presentation, making differential diagnosis challenging, especially in young children without other manifestations of NF1 [7].
• Noonan syndrome with multiple lentigines: This is another rare genetic disorder that can present with skin pigmentation abnormalities, including café au lait macules.
• Constitutive Mismatch Repair Deficiency (CMMRD): This is a rare genetic disorder characterized by the presence of multiple café au lait macules, among other symptoms. It is an important differential diagnosis for patients presenting with these skin lesions [9].

It's worth noting that Legius syndrome can often be misdiagnosed as NF1 due to the presence of multiple café au lait macules. However, Legius syndrome can be distinguished from NF1 by its distinct genetic and clinical features [8].