IGSF1 deficiency syndrome

IGSF1 Deficiency Syndrome: A Rare Endocrine Disorder

The IGSF1 deficiency syndrome, also known as X-linked IGSF1 deficiency syndrome, is a rare and fascinating clinical syndrome involving multiple endocrine systems. This condition is caused by mutations or deletions in the immunoglobulin superfamily, member 1 (IGSF

IGSF1 Deficiency Syndrome: Signs and Symptoms

IGSF1 deficiency syndrome, also known as X-linked IGSF1 deficiency, is a rare genetic disorder caused by mutations in the immunoglobulin superfamily member 1 (IGSF1) gene. The main clinical characteristics of this syndrome are:

• Congenital central hypothyroidism: This is a condition where the thyroid gland does not produce enough thyroid hormones from birth.
• Macroorchidism: This refers to an abnormally large size of the testicles, which can be present at birth or develop later in life.

In addition to these primary symptoms, males with IGSF1 deficiency syndrome may also experience:

• Delayed puberty: Boys with this condition may experience delayed pubertal development, including delayed testosterone rise.
• Hypoprolactinemia: This is a condition where the level of prolactin hormone in the blood is lower than normal.
• Increased body weight: Some individuals with IGSF1 deficiency syndrome may experience increased body weight.

It's worth noting that the severity and presence of these symptoms can vary among affected individuals. In some cases, testicular enlargement (macroorchidism) may be absent or only partially present.

References:

• [1] A recently uncovered X-linked syndrome, caused by loss-of-function of IGSF1, is characterized by congenital central hypothyroidism and macroorchidism.
• [2] In male patients, the X-linked IGSF1 deficiency syndrome is characterized by CeH, hypoprolactinemia, delayed puberty, macro-orchidism, and increased body weight ...
• [7] IGSF1 deficiency has X-linked inheritance and is mainly associated with congenital isolated central hypothyroidism of variable severity.
• [8] The main clinical characteristics of the IGSF1 deficiency syndrome are congenital hypothyroidism of central origin and macroorchidism. In a variable proportion ...
• [10] Jan 31, 2024 — X-linked IGSF1 deficiency syndrome is characterised in males by central hypothyroidism, delayed puberty, macro-orchidism, hypoprolactinemia, ...

Diagnostic Tests for IGSF1 Deficiency Syndrome

The diagnosis of IGSF1 deficiency syndrome can be challenging, but several diagnostic tests have been developed to aid in the identification of this condition.

• Genetic Testing: Specific genetic testing is performed using next-generation sequencing (NGS) of the entire coding region and the intronic flanking regions of the IGSF1 gene. This test can detect mutations in the IGSF1 gene, which are responsible for the syndrome [5][6].
• Clinical Characteristics: The diagnosis of IGSF1 deficiency syndrome is also based on a combination of clinical characteristics, including central hypothyroidism (CeH), delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency [10][12].
• Imaging Studies: Imaging studies such as ultrasound or MRI may be used to confirm the presence of macroorchidism in affected males [13].

Key Diagnostic Features

The key diagnostic features of IGSF1 deficiency syndrome include:

• Central hypothyroidism (CeH)
• Delayed pubertal testosterone rise
• Adult macroorchidism
• Variable prolactin deficiency
• Occasionally transient partial GH deficiency

These features can be used in conjunction with genetic testing to aid in the diagnosis of this condition.

References

[5] Specific genetic testing was performed using next-generation sequencing (NGS) of the entire coding region and the intronic flanking regions of the IGSF1, FOXE1, ...

[6] A recently uncovered X-linked syndrome, caused by loss-of-function of IGSF1, is characterized by congenital central hypothyroidism and macroorchidism, ...

[10] We previously reported that loss-of-function mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene in 11 families causes the X-linked IGSF1 deficiency syndrome.

[12] Context: Mutations in the immunoglobulin superfamily, member 1 (IGSF1) gene cause the X-linked IGSF1 deficiency syndrome consisting of central hypothyroidism, delayed pubertal testosterone rise, adult macroorchidism, variable prolactin deficiency, and occasionally transient partial GH deficiency.

[13] Immunoglobulin superfamily member 1 gene (IGSF1) defects are the molecular cause of a recently described X-linked syndrome including mild to moderate CeH.

The differential diagnosis of IGSF1 deficiency syndrome involves considering other conditions that may present with similar symptoms, such as central hypothyroidism and macroorchidism.

• Central Hypothyroidism: This condition is characterized by a deficiency in thyroid hormone production due to a problem with the pituitary gland. It can be caused by various factors, including genetic mutations, tumors, or inflammation.
• Prolactin Deficiency: Prolactin is a hormone produced by the pituitary gland that plays a crucial role in lactation and reproductive processes. A deficiency in prolactin can lead to symptoms such as delayed puberty, infertility, and galactorrhea (spontaneous milk production).
• Growth Hormone Deficiency: This condition occurs when the pituitary gland does not produce enough growth hormone, leading to short stature or delayed growth and development.
• Kallmann Syndrome: A rare genetic disorder characterized by delayed puberty, hypogonadotropic hypogonadism (low sex hormone levels), and anosmia (loss of smell).
• Pituitary Tumors: Non-cancerous tumors in the pituitary gland can cause hormonal imbalances, leading to symptoms such as central hypothyroidism, prolactin deficiency, or growth hormone deficiency.

To differentiate IGSF1 deficiency syndrome from these conditions, healthcare providers may perform various tests, including:

• Genetic Testing: To identify mutations in the IGSF1 gene and confirm a diagnosis of IGSF1 deficiency syndrome.
• Hormone Level Tests: To assess thyroid hormone, prolactin, growth hormone, and other hormone levels to rule out other conditions.
• Imaging Studies: Such as MRI or CT scans to visualize the pituitary gland and detect any tumors or abnormalities.

A comprehensive medical history, physical examination, and diagnostic testing are essential for accurate diagnosis and treatment of IGSF1 deficiency syndrome.