Sanjad–Sakati syndrome

Sanjad–Sakati Syndrome (SSS), also known as Hypoparathyroidism-Retardation-Dysmorphism Syndrome (HRDS), is a rare genetic disorder characterized by a spectrum of clinical features including hypoparathyroidism, growth retardation, and distinctive facial features. First described by Sanjad, Sakati, and colleagues in 1988, the syndrome is primarily reported in individuals of Middle Eastern descent, particularly those from the Arabian Peninsula.

Etiology and Genetics

Sanjad–Sakati Syndrome is caused by mutations in the TBCE gene, located on chromosome 1q42.3. This gene plays a crucial role in the proper folding and functioning of tubulin, which is essential for microtubule formation within cells. Mutations in the TBCE gene lead to a disruption in cellular processes, particularly affecting the development of the parathyroid gland, skeletal system, and neurological development. SSS is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected by the syndrome.

Clinical Features

The clinical presentation of Sanjad–Sakati Syndrome includes:

• Hypoparathyroidism: This leads to low levels of calcium in the blood (hypocalcemia) and high levels of phosphorus (hyperphosphatemia), causing seizures and tetany.
• Growth Retardation: Affected individuals exhibit intrauterine growth retardation (IUGR) and fail to achieve normal growth milestones.
• Distinctive Facial Features: These may include microcephaly (small head size), deep-set eyes, long philtrum, thin upper lip, and small hands and feet.
• Developmental Delay and Intellectual Disability: Varying degrees of cognitive impairment and developmental delays are common.
• Dental Anomalies: Delayed tooth eruption and enamel hypoplasia are frequently observed.

Diagnosis

Diagnosis of Sanjad–Sakati Syndrome is based on clinical evaluation and the presence of characteristic features. Genetic testing confirming a mutation in the TBCE gene provides a definitive diagnosis. Prenatal diagnosis is possible through genetic testing if there is a known risk of the syndrome in the family.

Management and Treatment

There is no cure for Sanjad–Sakati Syndrome, and treatment is symptomatic and supportive. Management strategies include:

• Calcium and Vitamin D Supplementation: To manage hypocalcemia and prevent seizures.
• Growth Hormone Therapy: May be considered to promote growth in some cases.
• Educational and Developmental Support: Tailored to the individual's needs to achieve maximum independence and quality of life.
• Regular Monitoring: For potential complications related to hypocalcemia and growth issues.

Prognosis

The prognosis for individuals with Sanjad–Sakati Syndrome varies depending on the severity of symptoms and the effectiveness of management strategies. Early diagnosis and intervention can improve the quality of life and mitigate some of the complications associated with the syndrome.

See Also

• Hypoparathyroidism
• Growth Retardation
• Genetic Disorders
• Autosomal Recessive Inheritance