Sanjad–Sakati syndrome

Lore & Background

Sanjad–Sakati syndrome was first reported from Saudi Arabia in 1988, but the first formal description is generally attributed to Sanjad et al. in 1991. It has since been observed in children from Qatar, Kuwait, Oman, and other Middle Eastern populations, as well as in offspring of Middle Eastern origin elsewhere. The condition is caused by abnormalities in the TBCE gene, located on chromosome 1q42.3, with identified deletions and mutations in affected individuals; rare cases exist where the disorder is not due to a TBCE gene abnormality.

Children with the syndrome typically present at birth with low birth weight due to intrauterine growth retardation and dysmorphism. The dysmorphic features include a long narrow face, deep-set small eyes, beaked nose, large floppy ears, microcephaly, thin lips with a long philtrum, and micrognathia. Other features include stunting, small hands and feet with long tapering fingers and clinodactyly, dental anomalies, low IGF-1 levels, and markedly retarded bone age.

The condition is characterized by hypoparathyroidism leading to episodes of hypocalcemia, hypocalcemic tetany, and hypocalcemic seizures. Immuno-reactive parathormone levels are low to undetectable, with low calcium and high phosphate levels in the blood. The moderate to severe intellectual disability is considered a primary feature of the syndrome, not merely a consequence of repeated seizures from low blood calcium.

Reader's Guide

Sanjad–Sakati syndrome is significant as a rare genetic disorder that highlights the importance of the TBCE gene in development and endocrine function. Its identification in Middle Eastern populations underscores the role of founder mutations and consanguinity in the prevalence of autosomal recessive conditions. The syndrome's triad of hypoparathyroidism, intellectual disability, and dysmorphism provides a clear diagnostic framework, though management remains supportive, focusing on controlling seizures and blood calcium levels. The condition's legacy includes advancing understanding of the genetic basis of hypoparathyroidism and growth disorders, and it serves as a model for studying gene–phenotype correlations in chromosome 1q42.3. Its documentation in the medical literature, first in Saudi Arabia and later across the Middle East, has aided in genetic counseling and prenatal diagnosis for at-risk families.

Did You Know?

• The condition is also called Hypoparathyroidism-Retardation-Dysmorphism (HRD) syndrome or Middle East syndrome.
• It is caused by mutations or deletions in the TBCE gene on chromosome 1q42.3.
• Children are typically born low-birth-weight due to intrauterine growth retardation.
• Dysmorphism includes a long narrow face, deep-set small eyes, beaked nose, and large floppy ears.