autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome

Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome, often called HANAC syndrome, is a very rare inherited disorder that affects blood vessels, kidneys, eyes, muscles, and other organs. It is caused by changes in the COL4A1 gene, which encodes a component of type IV collagen that helps strengthen the walls of small blood vessels and the kidney’s filtration system. Because these vessels become fragile, individuals can experience a mix of kidney bleeding, eye vessel abnormalities, and muscle problems that may appear in childhood, adolescence, or adulthood. The condition affects males and females equally and is thought to occur in fewer than one in a million people worldwide.

HANAC syndrome involves several body systems, and the combination of findings can vary greatly between individuals. The most consistent feature is marked tortuosity (twisting) of the small arteries in the retina, which is present in everyone studied and can lead to episodic retinal hemorrhages or blurred vision. Many individuals also have lifelong elevation of blood creatine kinase, reflecting underlying muscle involvement. Renal features often draw medical attention first. Some people notice visible blood in the urine (hematuria), while others are found to have microscopic blood cells during routine screening. Multiple kidney cysts and gradual loss of kidney function are common, although the degree of impairment differs from person to person. Muscle manifestations include painful leg cramps or spasms and, in some cases, congenital joint contractures that limit range of motion. Vascular and neurological complications arise from weakened vessel walls. These may include supraventricular heart rhythm disturbances, Raynaud phenomenon (color changes and discomfort in fingers and toes when cold), lacunar strokes, areas of white-matter change on brain imaging, and dilated cerebral arteries. Not all individuals experience all features, and severity ranges from mild to significant.

HANAC syndrome results from pathogenic variants in the COL4A1 gene. COL4A1 provides instructions for making one chain of type IV collagen, a structural protein crucial for the stability of basement membranes that line small blood vessels, glomeruli in the kidneys, and muscle tissue. Alterations in COL4A1 weaken these membranes, making vessels prone to leakage or damage and disrupting normal organ function. The condition follows an autosomal dominant inheritance pattern: a single altered copy of COL4A1 is sufficient to cause disease. If a parent carries the variant, each child has a 50 percent chance of inheriting it. Even within the same family, the specific symptoms and their intensity can differ markedly (variable expressivity). Genetic counseling is recommended for affected individuals and at-risk relatives to discuss testing and family-planning options.

Currently, management focuses on supportive care and monitoring rather than disease-specific medications. Kidney health is followed closely by a nephrologist, with blood-pressure control, avoidance of nephrotoxic drugs, and timely discussion of renal replacement options if function declines. Regular ophthalmologic examinations help detect retinal hemorrhages early; laser therapy or other interventions may be considered if vision is threatened. Neurological and vascular surveillance, such as periodic brain or arterial imaging and cardiac rhythm monitoring, aims to identify aneurysms, strokes, or arrhythmias before they become serious. Muscle cramps can be eased with stretching, adequate hydration, and medication if necessary. Because the syndrome affects several organ systems, long-term care usually involves a multidisciplinary team that may include nephrology, ophthalmology, neurology, cardiology, vascular surgery, and genetics. Regular surveillance is an essential part of long-term care, helping to identify potential complications before they become serious. Genetic counseling provides guidance on inheritance, testing of family members, and reproductive options.

Outcomes for individuals with HANAC syndrome vary widely. Some people maintain good kidney function and experience only mild muscle cramps or occasional eye symptoms, while others develop chronic kidney disease, vision problems, or vascular complications such as stroke. Close monitoring and prompt treatment of emerging issues can substantially improve quality of life and reduce serious events. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with specialists familiar with this condition and to seek ongoing genetic counseling as new information becomes available.