Sanjad-Sakati syndrome

Overview

Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, is a rare autosomal recessive genetic disorder characterized by a combination of congenital hypoparathyroidism, growth retardation, developmental delays, and distinct craniofacial features. The condition was first described by Drs. Sanjad and Sakati in Saudi Arabia and is most commonly reported in individuals of Middle Eastern descent, particularly in populations with high rates of consanguineous marriages.

Sanjad-Sakati syndrome presents in infancy or early childhood and is typically diagnosed due to severe hypocalcemia (low blood calcium levels), which can lead to seizures and neuromuscular irritability. The condition is caused by mutations affecting calcium regulation and development, and while there is no cure, early diagnosis and appropriate management can significantly improve outcomes. The syndrome is chronic and requires lifelong medical care.

Causes

Sanjad-Sakati syndrome is caused by mutations in the TBCE gene (tubulin-specific chaperone E), located on chromosome 1q42.3. This gene plays a critical role in the proper folding and assembly of tubulin proteins, which are essential for the structure and function of microtubules in cells. The mutation disrupts normal cellular functions, particularly in tissues involved in endocrine regulation, growth, and development.

The disorder is inherited in an autosomal recessive pattern, meaning a child must inherit two defective copies of the TBCE gene (one from each parent) to develop the condition. Carriers, who have only one mutated gene, do not show symptoms but can pass the mutation to their offspring. The risk of having an affected child increases when both parents are carriers, especially in closely related marriages.

Symptoms

Sanjad-Sakati syndrome manifests with a wide range of symptoms, primarily affecting calcium metabolism, physical development, and intellectual function. Common signs and symptoms include:

• Congenital hypoparathyroidism: Leads to low calcium and high phosphate levels, often resulting in seizures, muscle cramps, or tetany

• Growth retardation: Failure to thrive, short stature, and delayed bone development

• Intellectual disability: Ranging from mild to severe cognitive delays

• Craniofacial dysmorphism: Deep-set eyes, beaked nose, long philtrum, micrognathia (small jaw), and prominent ears

• Feeding difficulties: Poor sucking and swallowing in infancy

• Delayed milestones: Motor and speech development may be significantly delayed

• Recurrent infections: Possibly due to associated immune dysfunction or general failure to thrive

• Dental abnormalities: Delayed or abnormal tooth eruption

Not all affected individuals will have the full spectrum of symptoms, but hypocalcemia and dysmorphic features are almost always present.

Diagnosis

Diagnosis of Sanjad-Sakati syndrome is typically made in infancy or early childhood based on clinical features, biochemical tests, and confirmed through genetic testing. Diagnostic steps include:

• Blood tests: Revealing hypocalcemia, hyperphosphatemia, and low or inappropriately normal parathyroid hormone (PTH) levels

• Physical examination: Identification of characteristic facial features, growth failure, and developmental delay

• Neuroimaging: Brain imaging may show calcifications due to prolonged hypocalcemia

• Genetic testing: Confirms mutations in the TBCE gene, establishing a definitive diagnosis

Family history, especially in populations with consanguinity, may provide important clues. Carrier testing and prenatal diagnosis can be offered to at-risk families.

Treatment

There is no cure for Sanjad-Sakati syndrome, but treatment focuses on managing hypocalcemia, supporting growth and development, and preventing complications. A multidisciplinary approach is essential. Key aspects of treatment include:

• Calcium and vitamin D supplementation: Lifelong administration of calcium and active forms of vitamin D (e.g., calcitriol) to correct hypocalcemia

• Regular monitoring: Frequent checks of serum calcium, phosphate, and renal function to avoid complications like nephrocalcinosis

• Growth and nutrition support: Nutritional supplements and caloric support to manage feeding difficulties and promote weight gain

• Developmental therapies: Speech, occupational, and physical therapy to enhance cognitive and motor skills

• Antiepileptic medication: If seizures occur due to hypocalcemia or brain calcifications

• Genetic counseling: For affected families to understand inheritance patterns and reproductive options

Supportive care and regular follow-up with endocrinologists, pediatricians, and developmental specialists are essential for optimal management.

Prognosis

The prognosis for individuals with Sanjad-Sakati syndrome varies depending on the severity of hypocalcemia and the effectiveness of long-term management. With appropriate treatment, many symptoms can be controlled, and patients can have improved quality of life. However, most affected individuals will experience ongoing developmental challenges and require lifelong support.

Early diagnosis and consistent medical care can help prevent severe complications such as seizures, growth failure, and renal issues. Life expectancy may be reduced due to complications related to electrolyte imbalances and infections, but outcomes have improved with better awareness and treatment options. Continued research and supportive therapies offer hope for better management of this rare but serious condition.