Coffin-Siris syndrome 5

Coffin-Siris Syndrome 5: A Rare Congenital Disorder

Coffin-Siris syndrome 5, also known as CSS5, is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. This condition affects several body systems and can be caused by variants in one of several genes.

Key Features:

• Delayed psychomotor development
• Intellectual disability
• Coarse facial features
• Hypoplasia of the distal phalanges, particularly the fifth digit
• Other features may include congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly

Genetic Cause:

Coffin-Siris syndrome 5 is caused by variants in one of several genes, including ARID1A, ARID1B, SMARCA4, SMARCB1, DPF2, or SMARCE1. Variants in the ARID1B gene are the most common known cause of the condition.

Diagnosis:

Diagnosis of Coffin-Siris syndrome 5 occurs after birth when doctors notice fifth finger and toe abnormalities as well as facial abnormalities. Dysmorphic features tend to become more pronounced with age, and criteria for diagnosis are still evolving due to the rarity of the condition.

References:

• [1] Richieri-Costa A, et al. Coffin-Siris syndrome in a Brazilian child with consanguineous parents. Rev Brasil Genet.1986;IX:169-177.
• [2] Coffin-Siris syndrome is a rare congenital disorder characterized by delayed psychomotor development, intellectual disability, coarse facial features, and hypoplasia of the distal phalanges, particularly the fifth digit. Other features may also be observed, including congenital heart defects, hypoplasia of the corpus callosum, and poor overall growth with short stature and microcephaly ...
• [10] Coffin-Siris syndrome (CSS) is classically characterized by aplasia or hypoplasia of the distal phalanx or nail of the fifth and additional digits, developmental or cognitive delay of varying degree, distinctive facial features, hypotonia, hirsutism/hypertrichosis, and sparse scalp hair. Congenital anomalies can include malformations of the cardiac, gastrointestinal, genitourinary, and/or ...
• [11] Coffin-Siris syndrome is a genetic condition that causes variable degrees of learning disability, developmental delays, underdeveloped 'pinky' toenails or fingernails, and distinct facial features. It can be caused by a change in any of several genes including the ARID1A, ARID1B, SMARCA4, SMARCB1, DPF2 or SMARCE1 genes. ... Description. Absence ...
• [12] Coffin-Siris syndrome is caused by variants (also known as mutations) in one of several genes. Variants in the ARID1B gene are the most common known cause of the condition. Variants in the ARID1A, SMARCA4, SMARCB1, SMARCE1, or SOX11 gene can also cause the condition. In addition, variants in a few other genes (listed below) have been found to each cause a very small number of cases.
• [14] Coff–Siris syndrome (OMIM#135900) is a multiple congenital anomaly syndrome classically characterized by hypo- or aplasia of the fifth digit nails or phalanges, as well as coarse facial features, sparse scalp hair, and moderate to severe cognitive and/or developmental delay. ... characterize a large set of patients who have been described ...

Diagnostic Tests for Coffin-Siris Syndrome

Coffin-Siris syndrome (CSS) 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 signs such as intellectual disability, developmental delays, short stature, low muscle tone (hypotonia), and abnormally loose skin.
• Genetic Testing: Molecular genetic testing can confirm the diagnosis of CSS. This test involves analyzing the genes associated with the condition, which include sequence and deletion/duplication analysis of all the listed genes.

Detection Rate: The panel includes 22 genes that have been associated with Coffin-Siris syndrome phenotypes. According to a study [9], this test is expected to detect causative variants in about 60% of patients with CSS (Schrier Vergano et al., 2021).

Additional Tests: Prenatal diagnosis may also be prompted through ultrasound tests [8]. Healthcare providers may recommend imaging other parts of the body, such as X-rays or CT scans, to rule out other conditions.

References: [5] - The target population for this test is patients suspected of having a diagnosis of Coffin-Siris syndrome. Variant Interpretation: What is the protocol for ... [8] - Jan 8, 2024 — Prenatal diagnosis of Coffin-Siris syndrome may also be prompted through ultrasound tests. [9] - This test is expected to detect causative variants in about 60% of patients with Coffin-Siris syndrome (Schrier Vergano et al. 2021. PubMed ID: 23556151).

Treatment Options for Coffin-Siris Syndrome

Coffin-Siris syndrome, a rare genetic disorder, requires individualized treatment plans to address its various symptoms. While there is no specific "cure" for the condition, several treatment options can help manage its effects.

• Developmental and Cognitive Delays: Occupational, physical, and speech therapy can be beneficial in addressing developmental delays and cognitive impairments associated with Coffin-Siris syndrome.
• Surgical Repair: Surgical interventions may be necessary to correct certain craniofacial anomalies or other congenital malformations that can occur in individuals with this condition.
• Medication Management: In some cases, medications may be prescribed to manage symptoms such as attention-deficit hyperactivity disorder (ADHD) and autism, which often co-occur with Coffin-Siris syndrome.

It's essential to note that treatment for Coffin-Siris syndrome is highly individualized and depends on the specific presentation of the condition in each person. A multidisciplinary team of healthcare professionals, including geneticists, pediatricians, and specialists in various fields, should be involved in developing a comprehensive treatment plan.

References:

• [12] Treatment for Coffin-Siris syndrome may include occupational, physical, speech therapy. Surgical repair of certain craniofacial, ...

Differential Diagnoses for Coffin-Siris Syndrome

Coffin-Siris syndrome (CSS) can be challenging to diagnose due to its clinical variability and overlap with other syndromes. The following conditions are considered differential diagnoses for CSS:

• Nicolaides-Baraitser syndrome: This rare genetic disorder is characterized by intellectual disability, distinctive facial features, and various congenital anomalies.
• Brachymorphism-onychodysplasia-dysphalangism (BOD): A rare condition marked by short stature, abnormal nails, and skeletal abnormalities.
• DOOR syndrome: A rare genetic disorder featuring developmental delay, ophthalmologic abnormalities, hearing impairment, and other systemic features.
• Hyperphosphatasia-intellectual disability syndrome: A rare condition characterized by elevated serum alkaline phosphatase levels, intellectual disability, and various congenital anomalies.

These differential diagnoses are important to consider when evaluating patients with suspected CSS, as they can share similar clinical features. Accurate diagnosis requires a comprehensive evaluation of the patient's medical history, physical examination, and laboratory findings.

References:

• [8] - Feb 1, 2016
• [10] -
• [5] - by X Huang · 2024