Rare Genetic Syndrome Shows 38% Mortality by Age 18 with Respiratory Failure Leading Cause

Sanjad-Sakati syndrome (SSS) is a rare autosomal recessive disorder caused by a founder mutation in the TBCE gene. Characterized by hypoparathyroidism, severe intellectual disability, and distinctive facial features, SSS disproportionately affects populations in the Arabian Peninsula. Despite its severity, the full clinical spectrum and long-term outcomes have remained poorly defined due to the syndrome's rarity and geographic concentration.

Researchers conducted an international multicenter registry study collecting clinical and genetic data from 135 individuals across Saudi Arabia, Oman, and Kuwait using REDCap surveys. The cohort ranged from newborns to 30-year-olds, with a median age of 9.1 years and roughly equal sex distribution. All genetically tested patients carried the same homozygous TBCE founder mutation.

Key findings paint a sobering clinical picture. Severe intrauterine growth restriction was universal, and postnatal height z-scores remained extremely low (-7 to -8) throughout life. Every patient had hypoparathyroidism; additional endocrine complications included hypothyroidism in 16.5%, hypoglycemia in 27.8%, and pituitary hormone deficiencies. Hypocalcemic seizures affected 64%, nephrocalcinosis 62%, and recurrent respiratory infections 64%. Antibiotic prophylaxis was used in 35% of patients.

Mortality data are striking. Kaplan-Meier analysis estimated median survival at just 27.2 years, with only 62.4% of patients surviving to age 18. Respiratory failure was the cause in 84% of the 25 recorded deaths, highlighting airway and pulmonary management as the critical unmet clinical need.

These findings have direct implications for how SSS should be managed. The breadth of endocrine, respiratory, renal, and gastrointestinal complications demands a coordinated multidisciplinary approach. Clinicians caring for SSS patients — particularly in regions where consanguinity makes this mutation more prevalent — should anticipate multi-organ involvement and prioritize proactive respiratory monitoring and infection prevention strategies.