Overview
Barakat syndrome is a rare genetic disorder. Individuals with the syndrome usually present with hypoparathyroidism, sensorineural deafness and renal conditions although other less common symptoms can also be present. Barakat syndrome usually presents in early infancy and childhood but has been identified in older adults.1
Barakat syndrome is also sometimes called HDR syndrome and was first described in 1977 by Barakat et al.2
The genetic basis of the condition lies with mutations in the GATA3 gene located on chromosome 10p14.
The disorder has a wide range of clinical features and early diagnosis and management are vital for improving patient outcomes.
What is Barakat syndrome?
Barakat syndrome is a rare genetic disorder that is also known as HDR syndrome because of the presence of three key symptoms
- H hypoparathyroidism
- D sensorineural deafness
- R renal disease
The condition is caused by deletions in chromosome 10p14 or mutations in the GATA3 gene.3
Prevalence of Barakat syndrome
The prevalence of Barakat syndrome is rare. Until 2018, 180 patients have been reported in the literature2 and six further cases have been reported since then.1
In the last 20 years, the genetic mutations associated with Barakat syndrome have been reported in 124 families and 177 individuals.4
Symptoms of Barakat syndrome
Barakat syndrome has many symptoms including
- Hypoparathyroidism
- Sensorineural deafness
- Renal abnormalities
- Cardiac abnormalities
- Developmental delay
- Craniofacial features
Hypoparathyroidism
Hypoparathyroidism in Barakat syndrome occurs as a result of insufficient production of parathyroid hormone (PTH) which plays a key role in calcium homeostasis which leads to hypocalcaemia.
Hypoparathyroidism is a condition whereby the body produces abnormally low levels of parathyroid hormone which is vital for regulating and maintaining a balance of calcium and phosphorus. The reduced parathyroid hormone leads to abnormally low blood calcium levels and increased phosphorus.
Symptoms of hypoparathyroidism
The main symptom of hypoparathyroidism is hypocalcaemia. Hypocalcaemia means low blood calcium and can cause a range of mild to severe symptoms such as
Tetany
Tetany presents as involuntary muscle contractions and spasms, particularly in the hands and feet due to hypocalcaemia.
Seizures
Severe hypocalcaemia can cause seizures.
Muscle cramps and spasms
Frequent muscle cramping can be experienced due to hypocalcaemia.
Sensorineural deafness
Sensorineural deafness in Barakat syndrome is very common due to defects in the auditory nerve. The severity of hearing loss can vary from mild to profound and can be present from birth (congenital) or develop later in childhood.
Renal abnormalities
Renal abnormalities occur in Barakat syndrome. Some patients experience mild issues while others may progress to chronic kidney disease. Symptoms can include:
Renal dysplasia
Renal dysplasia results from abnormal development of kidney tissue. This leads to impaired renal function.
Nephrotic syndrome
Nephrotic syndrome causes proteinuria, hypoalbuminemia and oedema. It is usually caused by damage to small blood vessels in the kidneys.
Proteinuria
Excess protein in the urine due to renal damage is described as proteinuria.
Other symptoms of Barakat syndrome
Developmental delay
Developmental delay can also be seen in Barakat syndrome,
Craniofacial abnormalities
Craniofacial abnormalities are less common but can have functional impacts that require surgical interventions to improve quality of life.
Micrognathia
Micrognathia describes an unusually small jaw and can cause feeding and breathing difficulties.
Cleft palate
A cleft palate is a split in the roof of the mouth that can cause feeding and speech problems.
Cardiac anomalies
Cardiac issues can also be present with Barakat syndrome and can include
Ventricular septal defect
A ventricular septal defect is often referred to as VSD and describes a hole in the wall separating the lower chambers of the heart.
Atrial septal defect
An atrial septal defect is also known as ASD and is a hole in the wall between the upper chambers of the heart.
Clinical presentation of Barakat syndrome
The symptoms of Barakat syndrome can present at different stages of life
Neonatal period
Symptoms such as hypoparathyroidism and sensorineural deafness may be present at birth or early infancy
Childhood
Renal anomalies and developmental delays often become more apparent as the child grows.
Later life
There have been cases of diagnosis of Barakat syndrome in much later life too with varying degrees of the recognised symptoms.1,5,6
Symptom progression in Barakat syndrome
The progression of symptoms in Barakat syndrome can vary by individual. Some people may present with unusual symptoms or variations in the severity and combination of the core features.7
Early childhood development
Initial symptoms of Barakat syndrome may include feeding difficulties, delayed developmental milestones and hypocalcaemia.
Adulthood complications
Chronic renal disease and ongoing hearing loss management are concerns throughout the life of someone with Barakat syndrome. Long-term follow-up is essential to monitor and manage these conditions.
Diagnosis of Barakat syndrome
Genetic testing
Genetic testing plays a key role in diagnosing Barakat Syndrome by identifying structural changes on chromosome 10p14 and mutation of the GATA3 gene.
Diagnosis of hypoparathyroidism
Diagnosis of hypoparathyroidism can involve serum calcium measurements and parathyroid hormone levels, which are inappropriately low or normal in the presence of hypocalcaemia.
In patients with unexplained hypoparathyroidism associated with a history of sensorineural deafness or renal disease, Barakat syndrome should be considered for the patient and family members.8
Biochemical tests
Serum calcium and parathyroid hormone levels are measured when hypoparathyroidism is suspected. Low calcium or inappropriately normal PTH levels suggest hypoparathyroidism.
Diagnosis of hearing impairment
Audiometry
Audiometry or audiogram is a non-invasive hearing test used to determine an individual’s ability to hear sound.
Otoacoustic emissions
Otoacoustic emissions tests measure sound waves produced in the inner ear when stimulated by clicking sounds to assess cochlear function.
Diagnosis of renal abnormalities
Diagnosis of renal abnormalities will usually be by
Renal ultrasound scan
A renal ultrasound scan is used to examine the kidneys and detect structural abnormalities.
MRI scan
MRI scans can provide detailed imaging to assess renal tissue and function.
Blood tests
Blood samples will be taken to assess the serum levels of potassium, sodium, protein creatinine and blood urea nitrogen to evaluate kidney function.
Urinalysis
Urinalysis refers to the analysis of urine samples for protein, blood, sugar and other substances that can indicate evidence of renal abnormalities or rule them out.
Diagnosis of cardiac abnormalities
Diagnostic tools for identifying cardiac anomalies include
Echocardiogram: An echocardiogram uses ultrasound waves to create images of the heart and detect tissue or muscle damage.
Electrocardiogram: An electrocardiogram is also commonly known as an ECG and records the electrical activity of the heart to identify any cardiac rhythm abnormalities.
Management and treatment of Barakat syndrome
Medical management
Medical management focuses on addressing the primary symptoms of Barakat syndrome
Supplementation with these micronutrients is essential for managing hypoparathyroidism and preventing hypocalcaemia.
Management of renal issues
- medication
- dietary modifications such as restricted protein intake
- renal dialysis
- renal transplantation
Hearing aids and cochlear implants
Assistive devices such as hearing aids and cochlear implants can assist with sensorineural deafness and improve communication abilities.
Surgical interventions
Surgical interventions may be necessary for
- Correction of micrognathia and cleft palate to improve feeding, breathing and speech.
- Cardiac surgery to repair heart defects.
Management approach
A multidisciplinary approach is essential for comprehensive care in the presence of Barakat syndrome. Many different specialists may be involved and include
Long-term care plans
Regular follow-up and monitoring to manage the chronic aspects of the syndrome and prevent complications.
Prognosis in Barakat syndrome
Several factors influence the prognosis of Barakat syndrome
Severity of symptoms
Patients with milder forms of the syndrome may have a better prognosis.
Early intervention and management
Prompt diagnosis and comprehensive management improve outcomes significantly.
Long-term outcomes of Barakat syndrome
Long-term outcomes for patients with Barakat Syndrome vary. Early intervention and appropriate management can ensure a good quality of life, allowing individuals to lead relatively normal lives.
With proper management of hypoparathyroidism, renal issues and hearing loss, life expectancy with Barakat syndrome can be near normal and quality of life can be optimised.
Summary
Barakat Syndrome is a very rare and complex genetic disorder with a wide range of symptoms. It is also known as HDR syndrome due to the high prevalence of hypoparathyroidism, deafness and renal abnormalities.
Prompt diagnosis and intervention are crucial for effective management of the key symptoms. A multidisciplinary approach involving many different health professionals and genetic testing, biochemical assessments and audiological tests are essential for diagnosis and care.
With early intervention and appropriate management, individuals with Barakat syndrome can achieve a good quality of life and near-normal life expectancy.
References
- Spennato U, Siegwart J, Hartmann B, Fischer EJ, Bracco C, Capraro J, et al. Barakat syndrome diagnosed decades after initial presentation. Endocrinology, Diabetes & Metabolism Case Reports 2023;2023:23–0018. Available from: https://doi.org/10.1530/EDM-23-0018.
- Barakat AY, D’Albora JB, Martin MM, Jose PA. Familial nephrosis, nerve deafness, and hypoparathyroidism. The Journal of Pediatrics 1977;91:61–4. Available from: https://doi.org/10.1016/S0022-3476(77)80445-9.
- Barakat AJ, Raygada M, Rennert OM. Barakat syndrome revisited. American J of Med Genetics Pt A 2018;176:1341–8. Available from: https://doi.org/10.1002/ajmg.a.38693.
- Lemos MC, Thakker RV. Hypoparathyroidism, deafness, and renal dysplasia syndrome: 20 Years after the identification of the first GATA3 mutations. Human Mutation 2020;41:1341–50. Available from: https://doi.org/10.1002/humu.24052.
- Rego T, Fonseca F, Agapito A. Barakat syndrome: an uncommon cause of hypocalcaemia. EJEA 2015. Available from: https://doi.org/10.1530/endoabs.37.EP290.
- Garate Chirinos D, Pulgar Sedó I. SUN-522 Hypoparathyroidism: When to Suspect Barakat Syndrome: A Case Report. Journal of the Endocrine Society 2019;3:SUN-522. Available from: https://doi.org/10.1210/js.2019-SUN-522.
- Pan Y, Fu J. Case Report: Clinical Description of a Patient Carrying a 12.48 Mb Microdeletion Involving the 10p13–15.3 Region. Front Pediatr 2021;9:603666. Available from: https://doi.org/10.3389/fped.2021.603666.
- Gandolfi A, Ratnasamy K, Minutti C. Hypoparathyroidism, Sensorineural Deafness, and Renal Disease Syndrome Presenting With Febrile Seizures and Hypocalcemia. JCEM Case Reports 2022;1:luac025. Available from: https://doi.org/10.1210/jcemcr/luac025.
