IVIC syndrome

IVIC syndrome, also known as IVIC syndrome (IVIC), is a rare genetic disorder that affects various parts of the body.

Upper Limb Anomalies IVIC syndrome is characterized by upper limb anomalies, specifically radial ray defects and carpal bone fusion [1][3][7]. This can result in abnormalities such as extra fingers or toes, or other deformities of the hands and feet.

Extraocular Motor Disturbances In addition to upper limb anomalies, IVIC syndrome also involves extraocular motor disturbances, which affect the movement of the eyes [2][8].

Other Symptoms Some individuals with IVIC syndrome may experience hearing impairment, radial ray defects and hand anomalies, internal ophthalmoplegia (paralysis of one or more extraocular muscles), thrombocytopenia (low platelet count), and other symptoms [4][6].

Genetic Mutation IVIC syndrome is an autosomal dominant disorder, meaning that a single copy of the mutated gene is enough to cause the condition. It is caused by a genetic mutation that affects various parts of the body.

Overall, IVIC syndrome is a complex and rare genetic disorder that can affect multiple systems in the body.

IVIC syndrome, also known as oculo-oto-radial syndrome, is a rare genetic disorder characterized by several distinct signs and symptoms.

Upper Limb Anomalies

• Radial ray defects: This can include abnormalities in the formation of the radius bone in the forearm, leading to issues with arm movement and function.
• Carpal bone fusion: In some cases, the carpal bones in the wrist may fuse together, causing stiffness and limited mobility.

Extraocular Motor Disturbances

• External ophthalmoplegia: This refers to weakness or paralysis of the extraocular muscles that control eye movement, leading to difficulties with eye alignment and movement.
• Hearing loss: IVIC syndrome is also associated with congenital bilateral non-progressive mixed hearing loss, which means that both ears are affected and the hearing loss does not worsen over time.

Other Signs and Symptoms

• Hypertelorism: This refers to an abnormally wide distance between the eyes.
• Exophthalmos: This is a condition where the eyeballs protrude from their sockets.
• External strabismus: This is a type of crossed eyes, where the eyes do not align properly.
• Parrot-beaked nose: This is a rare facial feature associated with IVIC syndrome.
• Short upper lip and hypoplastic maxilla: These are other facial features that may be present in individuals with IVIC syndrome.

Additional Features

• Polydactyly: This refers to the presence of extra fingers or toes.
• Syndactyly: This is a condition where two or more fingers or toes are fused together.
• Limb reduction/long bone deficiencies: In some cases, IVIC syndrome may be associated with abnormalities in the formation of limbs or long bones.

It's essential to note that each individual with IVIC syndrome may exhibit a unique combination of these signs and symptoms. If you suspect that someone has IVIC syndrome, it is crucial to consult with a medical professional for an accurate diagnosis and proper care.

References:

• [1] IVIC syndrome (IVIC) is an autosomal dominant disorder characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral nonprogressive mixed hearing loss. ... signs and symptoms soon become apparent.
• [4] Symptoms. The list of signs and symptoms mentioned in various sources for Ivic Syndrome includes the 10 symptoms listed below: * Radial ray defects ...
• [7] Common features include hypertelorism, exophthalmos and external strabismus, parrot-beaked nose, short upper lip, hypoplastic maxilla, and a relative mandibular ...
• [9] Common clinical presentation includes polydactyly, syndactyly, limb reduction / long bone deficiencies, and multiple anomalies and/or generalized skeletal.
• [11] IVIC syndrome is a very rare genetic malformation syndrome characterized by upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral non-progressive mixed hearing loss. ...

IVIC syndrome, a rare genetic malformation syndrome, can be diagnosed through various diagnostic tests.

• Genetic testing: MLPA (Methylation-specific PCR) has been shown to have greater than 99% sensitivity for detecting deletion and duplication variants in the affected area [4]. Genetic testing can confirm the presence of mutations in the SALL4 gene, which is associated with IVIC syndrome [14].
• Clinical examination: A thorough clinical examination by a healthcare provider can help identify symptoms such as upper limb anomalies (radial ray defects, carpal bone fusion), extraocular motor disturbances, and congenital bilateral non-progressive mixed hearing loss [3, 6, 10].
• Radiographs: Upper limb radiographs can reveal radial ray defects and carpal bone fusion, which are characteristic features of IVIC syndrome [9, 12].
• Audiograms: Audiological evaluation is essential to confirm the presence of congenital bilateral non-progressive mixed hearing loss [6, 11].
• Ophthalmologic examination: An ophthalmologic examination can help identify extraocular motor disturbances and other eye-related abnormalities [3, 6].
• Blood cell count: A blood cell count may be performed to rule out thrombocytopenia, which is sometimes associated with IVIC syndrome [11].

It's essential to note that a diagnosis of IVIC syndrome should be made by a multidisciplinary team, including genetics, ophthalmology, and orthopedics specialists [10].

IVIC syndrome, a rare genetic condition, does not have a cure, but its symptoms can be managed through various treatments.

• Intravenous Immunoglobulin (IVIG): This is the standard-of-care treatment for patients with primary immunodeficiency diseases who have impaired antibody production and function. IVIG has been shown to significantly decrease inflammation in moderate to severe cases of IVIC syndrome [8][9].
• Immunoglobulin replacement therapy: This treatment is used to replace the missing or defective antibodies in patients with primary immunodeficiency diseases, including those with IVIC syndrome [14].

It's essential to note that these treatments are not curative and aim to manage the symptoms of IVIC syndrome. The effectiveness of these treatments may vary depending on individual cases.

References:

[8] - In moderate to severe cases, intravenous administration of immunoglobulins (IVIG) has been shown, in placebo-controlled trials, to significantly decrease inflammation. [9] - Intravenous immunoglobulin (IVIg) treatment can help you fight off infections if you have a weakened immune system or other diseases. [14] - Immunoglobulin replacement therapy is the standard-of-care treatment for patients with primary immunodeficiency diseases who have impaired antibody production and function.

Differential Diagnosis of IVIC Syndrome

IVIC syndrome, also known as oculo-oto-radial syndrome, is a rare genetic disorder characterized by upper limb and ocular abnormalities, congenital hearing loss, and extraocular motor disturbances. When diagnosing IVIC syndrome, it's essential to consider other conditions that may present with similar symptoms.

Conditions to Consider in Differential Diagnosis

• Holt-Oram Syndrome: A genetic condition affecting the upper limbs and heart, characterized by radial ray defects and congenital heart disease.
• Roberts Syndrome: A rare autosomal recessive disorder featuring limb abnormalities, including radial ray hypoplasia, and other systemic features.
• Fanconi Anemia: A genetic disorder that affects the bone marrow, leading to anemia, low white blood cell count, and increased risk of cancer.
• Thalidomide Embryopathy: A rare condition caused by prenatal exposure to thalidomide, characterized by limb abnormalities, including radial ray defects.
• VACTERL Association: A rare congenital disorder affecting the vertebrae, anus, trachea, esophagus, limbs, and kidneys.

Genetic Considerations

IVIC syndrome is inherited in an autosomal dominant manner, meaning a single copy of the mutated gene (SALL4) is sufficient to cause the condition. When diagnosing IVIC syndrome, it's crucial to consider other genetic conditions that may present with similar symptoms, such as Duane-radial ray syndrome (DRRS), acro-renal-ocular syndrome (AROS), and SALL4-related disorders.

Diagnostic Approach

A comprehensive diagnostic approach is essential for accurately diagnosing IVIC syndrome. This includes:

• Clinical Evaluation: A thorough physical examination to assess upper limb, ocular, and auditory abnormalities.
• Imaging Studies: Radiographic imaging of the upper limbs and other affected areas to confirm radial ray defects and other systemic features.
• Genetic Testing: Molecular genetic testing to identify mutations in the SALL4 gene or other genes associated with IVIC syndrome.

References

[3] Investigation on monozygotic twins indicated that modification of OORS gene expression must be environmental or epigenetic rather than genetic. [10] Consider a multigene panel that includes SALL4 and other genes of interest to identify the genetic cause of the condition while limiting identification of variants of uncertain significance and pathogenic variants in genes that do not explain the underlying phenotype.