Hutchinson-Gilford Progeria Syndrome (HGPS), often called progeria, is a rare and progressive genetic disorder causing children to age rapidly. Infants appear normal at birth, but signs of accelerated aging emerge within their first two years. HGPS is an extremely uncommon condition, affecting approximately 1 in 18 million to 1 in 20 million babies worldwide.
The Genetic Basis of HGPS
Hutchinson-Gilford Progeria Syndrome is caused by a mutation in the LMNA gene. This gene provides instructions for making the lamin A protein, a structural component of cell nuclei. A specific change in the LMNA gene leads to the production of an abnormal protein called progerin.
Progerin accumulates within the cell nucleus, contributing to its instability. This disrupts normal cellular functions and leads to the signs of premature aging. The mutation causing HGPS is almost always a spontaneous event, meaning it occurs de novo and is not inherited from a parent.
Signs and Symptoms
Children with HGPS appear healthy at birth, with symptoms becoming apparent between nine months and two years of age. Growth delays are among the first signs, leading to short stature and low body weight, often falling below the third percentile for their age.
Distinctive facial features develop as the condition progresses. These include prominent eyes, a thin nose with a beaked tip, thin lips, a small chin, and sometimes small ears without earlobes. Children experience widespread hair loss, affecting their scalp, eyelashes, and eyebrows. Their skin often appears thin, aged, and wrinkled, with visible veins, particularly on the scalp.
Body changes include a loss of subcutaneous fat and muscle, contributing to a frail appearance. Children also develop stiff joints, hip dislocations, and various bone abnormalities. Despite these physical manifestations, their intellectual development and motor skills, such as sitting and walking, remain appropriate for their age.
Diagnostic Process
The diagnostic process for Hutchinson-Gilford Progeria Syndrome begins with a physician’s observation of characteristic physical signs during a routine examination. Given the remarkably similar appearance among affected children, these visual cues often prompt further investigation. Physicians look for the specific combination of growth delays, distinctive facial features, and body changes that define the syndrome.
Once these clinical signs are noted, a definitive diagnosis is confirmed through a specific genetic blood test. This test analyzes the child’s DNA to identify the unique mutation in the LMNA gene. This provides a conclusive diagnosis of HGPS, distinguishing it from other conditions with similar features.
Management and Prognosis
Management of Hutchinson-Gilford Progeria Syndrome focuses on addressing symptoms and slowing disease progression. Lonafarnib, an FDA-approved medication, is a primary treatment that helps extend life expectancy for children with HGPS. This drug reduces the accumulation of progerin, the abnormal protein causing cellular instability.
Supportive therapies are part of comprehensive care. Physical and occupational therapy help manage joint stiffness and maintain mobility. Nutritional support aims to address growth delays and ensure adequate weight gain. Regular monitoring for cardiovascular issues is a significant aspect of care, as these children are prone to conditions like high blood pressure, heart failure, and accelerated hardening of arteries.
The prognosis for children with HGPS has improved with advancements in treatment. Without interventions, average life expectancy is around 14.5 years. With long-term medical treatment, including Lonafarnib, average life expectancy has increased to almost 20 years. The primary cause of mortality remains cardiovascular complications, such as heart attacks and strokes, resulting from accelerated arterial disease.