Nishihara Syndrome, also known as Nakajo-Nishimura syndrome, is a rare genetic condition that impacts multiple body systems. This inherited disorder can manifest with a range of physical characteristics and internal complications.
Defining Nishihara Syndrome
Nishihara Syndrome is characterized by a combination of symptoms that begin in infancy or early childhood. Individuals develop red, swollen lumps on the skin, known as nodular erythema, which are more pronounced in cold weather. Recurrent fevers are also common.
The syndrome also affects the skeletal system, leading to elongated fingers and toes with widened and rounded tips, called clubbing. Later in childhood, individuals may experience joint pain and contractures, deformities that restrict movement, particularly in the hands, wrists, and elbows. Muscle weakness and wasting, along with a loss of fatty tissue, especially in the upper body, are also present, leading to an extremely thin appearance in the face, chest, and arms.
Beyond these external manifestations, Nishihara Syndrome can involve various internal systems. Some individuals may develop an enlarged liver and spleen, known as hepatosplenomegaly. Blood abnormalities also include a shortage of red blood cells (anemia) and reduced platelet counts (thrombocytopenia). Abnormal calcium deposits in the basal ganglia, in the brain, also occur.
Genetic Roots and Inheritance Patterns
Nishihara Syndrome is caused by mutations in the PSMB8 gene. This gene provides instructions for creating a component of specialized cellular structures called immunoproteasomes. Immunoproteasomes are involved in the breakdown of proteins within cells, playing a role in the immune system and other cellular functions.
The syndrome follows an autosomal recessive inheritance pattern. This means that an individual must inherit two copies of the mutated PSMB8 gene, one from each parent, to develop the condition. If a person inherits only one copy of the mutated gene, they are considered a carrier and do not show symptoms of the syndrome. For families with a child affected by Nishihara Syndrome, there is a 25% chance that each subsequent child will also inherit two copies of the mutated gene and develop the condition.
While the exact mechanism by which PSMB8 mutations lead to all symptoms is still being investigated, abnormal inflammation is believed to contribute to many features, including skin lesions, fevers, and joint problems. Research also suggests that the PSMB8 gene may have a separate role in the maturation of fat cells. A deficiency in the protein it produces could interfere with fat cell development and function, explaining the observed lipodystrophy. Nishihara Syndrome shares a genetic basis with other conditions like CANDLE syndrome and JMP syndrome, all linked to PSMB8 mutations, suggesting they are related conditions.
Recognizing and Diagnosing the Syndrome
Recognizing Nishihara Syndrome begins with observing the characteristic signs and symptoms, particularly their onset in infancy or early childhood. These include recurrent fevers, red swollen skin lesions worsening in cold weather, and elongated, clubbed fingers and toes. As the condition progresses, joint pain, limited joint movement due to contractures, and visible muscle and fat wasting, especially in the upper body, further indicate the syndrome.
Diagnosis involves a thorough clinical evaluation by a healthcare professional, assessing the patient’s medical history and physical presentation. Imaging studies, such as CT scans, may be performed to look for features like basal ganglia calcification. Laboratory tests can reveal blood abnormalities. Genetic testing is the definitive method to confirm Nishihara Syndrome by identifying mutations in the PSMB8 gene. This is important for accurate diagnosis and genetic counseling.
Managing Symptoms and Support
Managing Nishihara Syndrome focuses on supportive and symptomatic care, as there is no cure. A multidisciplinary team of healthcare professionals works together to address the diverse symptoms. This team may include rheumatologists for joint issues, dermatologists for skin manifestations, and neurologists if neurological symptoms are present.
Various therapies are important for improving quality of life. Physical therapy can help maintain joint mobility and muscle strength, while occupational therapy assists individuals in adapting to daily activities despite physical limitations. Speech therapy may be beneficial if the syndrome affects communication or swallowing. Medications are often prescribed to manage symptoms, such as anti-inflammatory drugs for joint pain and fever, or other medications for blood count abnormalities or organ involvement.
Supportive care also extends to resources for individuals and their families. This can include nutritional counseling to address muscle and fat loss, psychological support to cope with the chronic condition, and connecting with patient advocacy groups. These resources provide valuable information, emotional support, and a sense of community for those affected by Nishihara Syndrome.