Barakat syndrome

Overview

Barakat syndrome, also known as HDR syndrome, is a rare genetic disorder characterized by the triad of Hypoparathyroidism, Deafness, and Renal (kidney) abnormalities. It was first described by Dr. Ayad Barakat and colleagues in the early 1970s. The condition affects multiple organ systems and can present with a wide range of severity. The syndrome is autosomal dominant in inheritance and is linked to mutations in the GATA3 gene, which plays a critical role in the development of the parathyroid glands, auditory system, and kidneys.

Causes

Barakat syndrome is primarily caused by mutations or deletions in theGATA3 genelocated on chromosome 10p14. GATA3 is a transcription factor essential for the embryonic development of the parathyroid glands, inner ear, and kidneys. Key causes include:

• Heterozygous mutations or deletions in the GATA3 gene

• Autosomal dominant inheritance pattern – one copy of the defective gene is sufficient to cause the disorder

• De novo mutations – occur spontaneously in individuals with no family history

Symptoms

The presentation of Barakat syndrome can vary from mild to severe and includes a combination of endocrine, auditory, and renal symptoms:

• Hypoparathyroidism – leads to low calcium levels, causing muscle cramps, tetany, or seizures

• Sensorineural deafness – typically bilateral and moderate to severe; may be congenital or progressive

• Renal anomalies – may include renal hypoplasia, dysplasia, cysts, vesicoureteral reflux, or even end-stage renal disease

• Developmental delay or learning difficulties in some cases

• Facial dysmorphism may be present but is not a consistent feature

Diagnosis

Diagnosis is based on the clinical triad and confirmed through genetic testing:

• Blood tests to detect hypocalcemia, low parathyroid hormone (PTH), and possible renal dysfunction

• Hearing assessment – including audiometry and brainstem auditory evoked responses (BAER)

• Renal imaging – such as ultrasound or CT scan to assess kidney structure and function

• Genetic testing to identify mutations or deletions in the GATA3 gene

• Family history evaluation to identify inherited patterns

Treatment

There is no cure for Barakat syndrome; treatment is symptomatic and requires multidisciplinary management:

• Calcium and vitamin D supplementation to manage hypoparathyroidism and maintain normal calcium levels

• Hearing aids or cochlear implants for individuals with sensorineural deafness

• Management of renal dysfunction – including medications, dietary adjustments, or dialysis in severe cases

• Monitoring of growth and development, especially in children

• Regular follow-up with endocrinology, nephrology, audiology, and genetics teams

Prognosis

The long-term outcome of Barakat syndrome depends on the severity of organ involvement and the effectiveness of symptom management:

• Hearing and calcium levels can often be well-managed with proper treatment

• Renal disease may progress to chronic kidney disease or end-stage renal failure, requiring long-term management

• Life expectancy may be normal with appropriate care, especially if kidney complications are controlled

• Early diagnosis and multidisciplinary care greatly improve quality of life