Short Stature, Developmental Delay, And Congenital Heart Defects

A number sign (#) is used with this entry because of evidence that a syndrome involving short stature, developmental delay, and congenital heart defects (SDDHD) is caused by homozygous or compound heterozygous mutation in the TKT gene (606781) on chromosome 3p21.

Clinical Features

Boyle et al. (2016) studied 3 families, identified through whole-exome sequencing, in which 5 affected individuals had proportionate short stature, developmental delay, and congenital heart defects, including ventricular septal defect, atrial septal defect, patent foramen ovale, and patent truncus arteriosus. Measured IQ scores in 2 patients were 75 and 87, and 2 of the patients were nonverbal.

Molecular Genetics

By whole-exome sequencing in 2,625 individuals with neurodevelopmental disorders, Boyle et al. (2016) identified 3 probands and 2 additional family members from 3 unrelated families with homozygous (606781.0001) or compound heterozygous (606781.0002-606781.0003) mutations in the TKT gene. Affected individuals in the 3 families exhibited short stature, developmental delay, and congenital heart defects. Cell extracts from all 5 patients showed absent or low residual TKT activity. Boyle et al. (2016) suggested that the low TKT activity in some tissues, possibly from another protein with the same function, might explain why TKT deficiency is compatible with life even though TKT is an essential enzyme.