Legius syndrome

What is legius? syndrome?

Legius syndrome is rare genetic disorder that was first described in 2007 [1]. Also known as neurofibromatosis type 1 syndrome [2].

Legius syndrome is classically characterized by light brown multiples. macules, known as café-au-lait macules [3]. Unlike neurofibromatosis type 1, no tumors are found in Legius syndrome.

Who gets Legius syndrome?

Legius syndrome can occur in anyone who has at least one biological parent with genetically confirmed Legius syndrome. [two]. the predominance Legius syndrome is unknown, but may be greater than expected due to misdiagnosis of type 1 neurofibromatosis [4].

What causes Legius syndrome?

Legius syndrome is an inherited genetic condition in a autosomal dominant way that involves a SPRED1 gene mutation in chromosome 15q14. This mutation results in the abnormal function of the SPRED1 protein, which is responsible for regulating the specific cellular signaling pathways involved in the cell. proliferation, differentiationand apoptosis. None other pathogen Variants have been found to cause Legius syndrome [2,3].

As a autosomal dominant condition, Legius syndrome can occur in anyone with at least one biological parent with genetically confirmed Legius syndrome. Rarely, it can also occur. de novoBut these cases have not been sufficiently evaluated to confirm this [2]. Every child with a parent with genetically confirmed Legius syndrome has a 50% risk of inheriting the condition.

What are the clinical features of Legius syndrome?

The clinical features of Legius syndrome vary significantly in nature and severity from one person to another.

Almost all patients with Legius syndrome have multiple café au lait macules [2,3]. The number of these macules tends to increase during childhood. [4].

Another common cutaneous Features may include:

• Freckles in the armpit and inguinal regions

• Lipomas [2–4].

Non-cutaneous features may include:

• Macrocephaly
• Unusual facial features, similar to Noonan syndrome
• Short stature
• Pectus excavatum (sunken sternum) or pectus carinatum (protruding sternum) [2–4].

Neuropsychiatric features may include:

• Learning difficulties
• Developmental delay
• Attention deficit hyperactivity disorder (ADHD) [2–4].

Intellectual disabilities are generally less severe in patients with Legius syndrome compared to patients with neurofibromatosis type 1 [5].

It is important to note that Legius syndrome does not cause neurofibromas and Lisch nodules, which are generally seen in neurofibromatosis type 1 [2,3].

How is Legius syndrome diagnosed?

Legius syndrome is difficult to diagnose on a clinical basis alone given its cutaneous clinical presentation similar to other café-du-lait multiple macule disorders.

When Legius syndrome is suspected, genetic tests can be used to confirm the diagnosis. This involves:

• Sequence analysis of SPRED1
• Elimination / duplication analysis (if the sequence analysis is not noticeable)
• A panel of multiple genes for SPRED1 and another genes of interest [2,3].

Suspicious findings that may warrant genetic testing for Legius syndrome include:

• Café au lait macules without other clinical features, suggesting neurofibromatosis type 1

• A father with café au lait macules without clinical features, again suggesting neurofibromatosis type 1 [2].

Which is the differential diagnosis for Legius syndrome?

Legius syndrome is often misdiagnosed because its pigmentary manifestations are very similar to those seen in other syndromes with multiple lentigines. Correct diagnosis is critical to guide long-term monitoring and management.

Neurofibromatosis type 1

• Neurofibromatosis type 1 is the most common misdiagnosis due to its similar clinical diagnostic criteria. [2–4].

• Neurofibromas, Lisch's nodules, bone abnormalities, and optic gliomas do not occur in Legius syndrome.
• These two conditions are difficult to differentiate in younger children, since the characteristic tumors seen in neurofibromatosis generally do not develop until later in life.

Noonan syndrome with multiple lentigines.

• Noonan syndrome with multiple lentigines (formerly known as LEOPARD syndrome, involves cardiovascular, ear, and genital abnormalities, which do not occur in Legius syndrome [6].

Other syndromes characterized by multiple lentigines include:

• Autosomal dominant café-au-lait macules

• McCune-Albright syndrome.

What is the treatment for Legius syndrome?

Children with Legius syndrome should undergo regular screening and evaluation for developmental delay, cognitive decline, and behavioral problems. [two].

Treatment of Legius syndrome is primarily supportive and should focus on the specific problems of the affected individual.

Proper management, if indicated, may include:

• Physical, speech and / or occupational therapy
• Behavior modification therapy and drug therapy (ie, for ADHD) [2].

What is the result of Legius syndrome?

Patients with Legius syndrome have good general behavior. forecast with proper problem-based management.

An affected person should consider the 50% risk of genetic transmission to each child.