Fechtner syndrome

Overview

Fechtner syndrome is a rare inherited disorder classified as a variant of Alport syndrome. It is characterized by a combination of kidney disease, hearing loss, and eye abnormalities, along with distinct blood cell findings, including leukocyte inclusions and macrothrombocytopenia (abnormally large and reduced number of platelets). The syndrome follows an autosomal dominant inheritance pattern and typically manifests in adolescence or early adulthood, although symptoms may vary in severity among affected individuals.

Causes

Fechtner syndrome is caused by mutations in the MYH9 gene, which encodes for non-muscle myosin heavy chain IIA. This protein plays a crucial role in cell structure and function, particularly in platelets, kidneys, and the inner ear. The genetic defect leads to cellular dysfunctions that affect various organs and systems. Fechtner syndrome is part of a group of disorders known as MYH9-related disorders, which also include May-Hegglin anomaly, Sebastian syndrome, and Epstein syndrome.

Symptoms

Fechtner syndrome presents with a variety of clinical features that often overlap with Alport syndrome. Common symptoms include:

• Kidney disease: Hematuria (blood in urine), proteinuria, and progressive renal insufficiency that can lead to end-stage renal disease (ESRD).

• Hearing loss: Sensorineural deafness, usually bilateral and progressive.

• Eye abnormalities: Cataracts, lenticonus (conical deformation of the lens), and retinal anomalies.

• Thrombocytopenia: Low platelet count with large platelets (macrothrombocytopenia), increasing the risk of bleeding.

• Leukocyte inclusions: Basophilic inclusion bodies visible in neutrophils under a microscope.

Diagnosis

Diagnosis of Fechtner syndrome is based on clinical features, laboratory findings, and genetic testing. Key diagnostic steps include:

• Urinalysis: Detects hematuria and proteinuria indicative of kidney involvement.

• Complete blood count (CBC): Shows thrombocytopenia and abnormally large platelets.

• Peripheral blood smear: Identifies Döhle-like inclusion bodies in neutrophils.

• Hearing tests: Audiometry to assess sensorineural hearing loss.

• Ophthalmologic examination: To detect lens and retinal abnormalities.

• Genetic testing: Confirms the diagnosis by identifying mutations in the MYH9 gene.

• Kidney biopsy: May be performed to evaluate the extent of renal damage, showing typical glomerular changes.

Treatment

There is no cure for Fechtner syndrome, and treatment focuses on managing individual symptoms and preventing complications. Treatment approaches include:

• Nephrology care: Use of ACE inhibitors or ARBs to reduce proteinuria and slow kidney disease progression.

• Dialysis or kidney transplantation: For patients who develop end-stage renal disease.

• Hearing aids or cochlear implants: To manage sensorineural hearing loss.

• Ophthalmologic interventions: Cataract surgery or vision support for visual impairments.

• Hematology management: Monitoring and managing bleeding risk in patients with low platelet counts; platelet transfusions may be needed before surgical procedures.

• Genetic counseling: For affected individuals and their families.

Prognosis

The prognosis for individuals with Fechtner syndrome varies depending on the severity of kidney involvement and associated complications. Renal disease progression may lead to end-stage renal failure, requiring dialysis or transplantation. Hearing and visual impairments can affect quality of life but are manageable with supportive therapies. Early diagnosis, regular monitoring, and a multidisciplinary approach to care can help improve long-term outcomes for affected individuals.