Sanjad-Sakati syndrome

Sanjad-Sakati syndrome (SSS), also known as hypoparathyroidism-retardation-dysmorphism (HRD) syndrome, is a rare autosomal recessive disorder first described in Middle Eastern populations, particularly among individuals of Arab descent. It is caused by mutations in the TBCE gene (tubulin-specific chaperone E) located on chromosome 1q43-q44. The condition is characterized by congenital hypoparathyroidism leading to severe hypocalcemia, which often presents with seizures in the neonatal or early infantile period. Affected individuals exhibit intrauterine and postnatal growth retardation resulting in severe short stature, intellectual disability, and distinctive facial features including deep-set eyes, thin lips, depressed nasal bridge, micrognathia, and small hands and feet. The syndrome primarily affects the endocrine system (parathyroid glands), skeletal system, and central nervous system. Hypocalcemia due to hypoparathyroidism is a hallmark feature and can cause life-threatening seizures if untreated. Additional features may include microcephaly, osteosclerosis, and medullary stenosis of long bones. Some patients may also have ocular abnormalities and recurrent infections. The condition shares clinical overlap with Kenny-Caffey syndrome type 1, which is also caused by TBCE mutations, and the two conditions are considered allelic disorders. There is no cure for Sanjad-Sakati syndrome. Treatment is primarily supportive and focuses on managing hypocalcemia through lifelong calcium and active vitamin D (calcitriol) supplementation to maintain adequate serum calcium levels and prevent seizures. Growth hormone therapy has generally not been effective for the short stature. Early intervention programs, developmental support, and regular monitoring of calcium and phosphorus levels are essential components of long-term management. Genetic counseling is recommended for affected families.

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