Summary about Disease
X-linked acrogigantism (X-LAG) is a very rare genetic disorder characterized by the onset of excessive growth and gigantism in early childhood, typically before the age of 5 years. It is caused by a microduplication on the X chromosome involving the GPR101 gene, leading to its over-expression. This over-expression results in increased growth hormone (GH) secretion, leading to accelerated growth velocity and features of gigantism.
Symptoms
Excessive linear growth, significantly exceeding age-related norms.
Accelerated growth velocity.
Large hands and feet (acromegaly).
Facial features of acromegaly (e.g., prominent forehead, jaw).
Macrocephaly (enlarged head size).
Possible associated intellectual disability, learning difficulties, or behavioral problems.
Increased appetite.
Hyperhidrosis (excessive sweating).
Headaches.
Causes
X-LAG is caused by a microduplication on the X chromosome at Xq26.3. This duplication includes the GPR101 gene, leading to its over-expression. GPR101 is thought to play a role in regulating GH secretion. The over-expression of GPR101 causes excessive GH production, resulting in acrogigantism. The condition is X-linked, meaning that males with the duplication will typically be more severely affected than females.
Medicine Used
Treatment primarily focuses on managing the excessive GH secretion and its effects:
Somatostatin analogs: Medications such as octreotide or lanreotide are used to suppress GH secretion.
GH receptor antagonists: Pegvisomant blocks the action of GH at its receptor.
Surgery: Transsphenoidal surgery to remove any pituitary tumor (although tumors are not always present in X-LAG).
Other supportive therapies: Management of associated conditions (e.g., hyperhidrosis, headaches) may require specific medications.
Is Communicable
No, X-linked acrogigantism is not communicable. It is a genetic disorder caused by a chromosomal duplication.
Precautions
Since X-LAG is a genetic condition, precautions are not applicable in the way they would be for an infectious disease. The focus is on:
Genetic counseling: For families with a history of X-LAG or suspected cases, genetic counseling can help assess recurrence risk and provide information.
Early diagnosis and management: Early diagnosis and intervention are crucial to manage the condition and minimize complications.
Regular monitoring: Ongoing monitoring of growth, GH levels, and other relevant parameters is important to adjust treatment as needed.
How long does an outbreak last?
X-linked acrogigantism is not an outbreak-related disease. It is a chronic condition that persists throughout the individual's life unless effectively managed through treatment.
How is it diagnosed?
Diagnosis involves:
Clinical evaluation: Assessment of growth patterns, physical examination for features of acrogigantism.
Hormonal testing: Measurement of GH and IGF-1 levels. Elevated levels are suggestive of the condition.
Genetic testing: Chromosomal microarray or other genetic tests to detect the duplication on the X chromosome involving the GPR101 gene.
MRI of the pituitary gland: To rule out pituitary adenoma, although tumors are not always present in X-LAG.
Timeline of Symptoms
The timeline of symptoms generally unfolds as follows:
Early Childhood (typically before age 5): Onset of accelerated growth.
Childhood: Continued excessive growth, enlarged hands and feet, facial features of acromegaly become more apparent.
Adolescence (if untreated): Progression of acromegalic features, potential development of complications related to excessive GH secretion (e.g., diabetes, cardiovascular issues).
The timeline varies considerably depending on the severity of GPR101 over-expression and the promptness and effectiveness of treatment.
Important Considerations
X-LAG is a very rare condition, so diagnosis can be challenging.
Early diagnosis and treatment are essential to manage growth and prevent complications.
The severity of the condition can vary among individuals.
Genetic counseling is important for families with affected individuals.
Long-term monitoring is necessary to manage GH levels and associated health issues.
Patients may require a multidisciplinary approach involving endocrinologists, geneticists, neurosurgeons, and other specialists.