X-linked intellectual disability-acromegaly-hyperactivity syndrome

X-linked intellectual disability-acromegaly-hyperactivity syndrome is a rare neurodevelopmental condition that includes severe intellectual deficits, acromegalic facial features, and hyperactivity. Affected individuals may also experience speech difficulties, aggressive behavior, and enlarged testes. This condition has been seen in two half-brothers, while their mother showed milder intellectual and facial features, suggesting an X-linked pattern. Brain imaging studies have identified central nervous system anomalies such as subarachnoid cysts and changes in the pons. The condition is very rare, affecting fewer than 1 in 1 million people. The severity and specific features can vary considerably from person to person.

Individuals with this syndrome present with a range of clinical features that affect both neurological and endocrine systems. The most prominent findings include profound intellectual disability, hyperactivity, and aggressive behavior, along with dysarthria that impacts speech. The distinctive facial appearance featuring a triangular, acromegalic face with a long nose, coupled with macroorchidism in affected males, forms a key part of the clinical picture. Additional findings such as decreased serum insulin-like growth factor 1, elevated circulating growth hormone levels, and central nervous system anomalies further underscore the complexity of this condition. Not all individuals experience all features, and severity varies considerably.

The precise genetic basis of X-linked intellectual disability-acromegaly-hyperactivity syndrome is currently under investigation. Although the condition is designated as X-linked in its name, no specific gene has been identified in the available data. This suggests that while males may be more severely affected, females might exhibit milder manifestations if they carry the underlying genetic change. Given these uncertainties and the possibility of variable expression, families are encouraged to seek genetic counseling to better understand potential risks and implications for family members.

Currently, management of X-linked intellectual disability-acromegaly-hyperactivity syndrome focuses on supportive care and symptom management. Treatment is tailored to each individual and typically involves a multidisciplinary team to address intellectual disability, speech difficulties such as dysarthria, behavioral challenges including hyperactivity and aggression, and endocrine abnormalities related to acromegaly. In the absence of a specific gene-targeted therapy, interventions may include behavioral therapies, educational support, and regular monitoring of endocrine function. Patients should discuss treatment options with their healthcare team to determine which therapies may be appropriate for their specific situation, and genetic counseling is recommended.

The long-term outlook for individuals with X-linked intellectual disability-acromegaly-hyperactivity syndrome is variable, with outcomes that depend on the severity of symptoms, age at diagnosis, and access to comprehensive care. With current standards of care, many individuals benefit from multidisciplinary management that addresses both neurodevelopmental and endocrine aspects of the condition. Outcomes described in medical literature continue to evolve as standards of care improve, and families often experience a course marked by an initial severe presentation followed by periods of stabilization. It is advisable for families to connect with specialists including genetic counselors, who can provide guidance and help navigate ongoing care.