Coffin-Siris syndrome 4

Coffin-Siris Syndrome 4 Description

Coffin-Siris syndrome 4 (CSS4) is a rare genetic condition characterized by various degrees of developmental delay, intellectual disability, and physical abnormalities.

• Developmental Delay: Individuals with CSS4 often experience delays in speech, motor skills, and cognitive development. [6]
• Intellectual Disability: The disorder may result in mild to severe intellectual disability, affecting an individual's ability to learn, reason, and interact with their environment. [7]
• Physical Abnormalities: Physical characteristics of CSS4 include coarse facial features, underdeveloped pinky toenails or fingers, and other distinctive physical traits. [3][8]

CSS4 is caused by heterozygous mutations in the SMARCA4 gene, which plays a crucial role in DNA repair and transcription regulation. [6] The condition is inherited in an autosomal dominant pattern, meaning that only one copy of the mutated gene is necessary to cause the disorder.

Key Features

• Developmental delay and intellectual disability
• Coarse facial features
• Underdeveloped pinky toenails or fingers
• Distinctive physical traits

References

[3] - Context result 3: "Coffin-Siris syndrome is a congenital malformation syndrome characterized by developmental delay, intellectual disability, coarse facial features, feeding..."

[6] - Context result 6: "Coffin-Siris syndrome 4 is an autosomal dominant congenital malformation syndrome caused by heterozygous mutations in the SMARCA4 gene."

[7] - Context result 7: "Aug 30, 2021 — Most affected individuals have mild to severe intellectual disability or delayed development of speech and motor skills such as sitting and..."

[8] - Context result 8: "Sep 6, 2024 — It's characterized by developmental disability, physical abnormalities of the pinky toes and fingers, as well as distinctive, “coarse” facial..."

Symptoms of Coffin-Siris Syndrome

Coffin-Siris syndrome (CSS) is a genetic condition that affects various aspects of an individual's development. The symptoms of CSS can vary in severity, but they often include:

• Intellectual disability: Individuals with CSS may experience significant delays in cognitive and intellectual development [4].
• Delayed motor skills: People with CSS might exhibit delayed or impaired motor skills, affecting their ability to perform daily tasks and activities [4].
• Underdevelopment of fingers and toes: One of the characteristic features of CSS is the underdevelopment or absence of the distal phalanx (the tip) of the fifth finger, also known as "pinky" toenails or fingernails [3][8].
• Absence of the distal phalanx: This symptom is a hallmark of CSS and can be observed in most individuals with the condition [4].

Other symptoms associated with Coffin-Siris syndrome include:

• Coarse facial features: Individuals with CSS may have distinctive facial characteristics, such as a wide nose, flat nasal bridge, wide mouth, thick lips, and thick eyebrows and eyelashes [5][9].
• Short stature: Some people with CSS might experience short stature or growth delays [7][1].
• Low muscle tone (hypotonia): Individuals with CSS may have low muscle tone, which can lead to abnormally loose skin and muscles [7].

It's essential to note that the severity and combination of symptoms can vary significantly among individuals with Coffin-Siris syndrome.

Diagnostic Tests for Coffin-Siris Syndrome

Coffin-Siris syndrome can be diagnosed through a combination of clinical evaluation and genetic testing.

• Clinical Evaluation: The diagnosis is generally based on the presence of major and at least one minor clinical sign. A physical examination by a healthcare provider may reveal symptoms such as sucking/feeding difficulties, poor growth, ophthalmologic abnormalities, hearing impairment, and spinal anomalies [10].
• Genetic Testing: Molecular genetic testing can confirm the diagnosis by identifying causative variants in the genes associated with Coffin-Siris syndrome. This test is expected to detect causative variants in about 60% of patients with Coffin-Siris syndrome [6].

Specimen Requirements for Genetic Testing

The following specimens can be used for genetic testing:

• Cord blood
• Fibroblasts
• Fresh tissue
• Isolated DNA
• Peripheral (whole) blood
• Saliva
• Skin

It's essential to consult with a healthcare provider to determine the best course of action and specimen requirements for diagnostic testing [5].

Unfortunately, there isn't much information available on specific drug treatments for Coffin-Siris Syndrome in the search results provided.

However, based on the context:

• There is no mention of any specific drugs or medication being used to treat Coffin-Siris Syndrome.
• Treatment is described as "supportive and symptomatic" (result 5), which suggests that treatment focuses on managing symptoms rather than using medications.
• One result mentions acetate supplementation (result 7) but it's not clear if this is a specific treatment for Coffin-Siris Syndrome or just a general finding.

It appears that the primary approach to treating Coffin-Siris Syndrome is through occupational, physical, and speech therapy (results 2, 5, 8), as well as surgical repair of certain craniofacial abnormalities (result 8).

Therefore, it's difficult to provide specific information on drug treatment for Coffin-Siris Syndrome based on the search results provided.

Differential Diagnoses for Coffin-Siris Syndrome

Coffin-Siris syndrome, a rare genetic disorder, can be challenging to diagnose due to its variable presentation. Several conditions share similar symptoms with Coffin-Siris syndrome, making differential diagnosis essential.

• Nicolaides-Baraitser syndrome: This condition is characterized by intellectual disability, facial abnormalities, and short stature. Like Coffin-Siris syndrome, it often involves developmental delays and learning disabilities.
• Brachymorphism-onychodysplasia-dysphalangism (BOD): BOD syndrome is a rare genetic disorder that affects the development of limbs, nails, and fingers. It can present with similar symptoms to Coffin-Siris syndrome, such as short stature, intellectual disability, and facial abnormalities.
• DOOR syndrome: DOOR syndrome is a rare genetic disorder characterized by developmental delays, intellectual disability, and distinctive facial features. It shares some similarities with Coffin-Siris syndrome in terms of its impact on development and learning abilities.
• Hyperphosphatasia-intellectual disability syndrome: This condition is associated with elevated levels of alkaline phosphatase, intellectual disability, and various physical abnormalities. While it has distinct characteristics, it can be considered in the differential diagnosis for Coffin-Siris syndrome.

These conditions highlight the importance of comprehensive diagnostic evaluation to accurately diagnose Coffin-Siris syndrome. A thorough medical history, physical examination, and genetic testing are often necessary to confirm a diagnosis.

References:

• [3] Differential diagnoses include Nicolaides-Baraitser syndrome, brachymorphism-onychodysplasia-dysphalangism, DOOR syndrome, hyperphosphatasia-intellectual ...
• [4] Aug 30, 2021 — Variants in the ARID1B gene are the most common known cause of the condition. Variants in the ARID1A, SMARCA4, SMARCB1, SMARCE1, or SOX11 gene ...