TPFS is a multi-system disorder characterized by developmental delay/intellectual disability, impaired growth, neonatal/childhood hypotonia, facial dysmorphism, and congenital malformations.
TPFS is a rare condition. The exact prevalence of TPFS is currently unknown. The Deciphering Developmental Disorders (DDD) project have exome sequenced ~13,500 patients with developmental disorders and found 3 patients with TPFS (Deciphering Developmental Disorders Study 2015; Turnpenny et al. 2018). More studies are needed to determine an unbiased population prevalence of the syndrome.
All TPFS patients to date have had a missense substitution at amino acid 65 of the PCGF2 protein. It is inherited in an autosomal dominant manner. However, almost all cases result from a de novo mutation. Therefore, most affected individuals represent simplex cases, i.e., a single occurrence in a family. If the mutation cannot be detected in either parent the recurrence risk for future pregnancies is probably low (e.g. <1%) but greater than that of the general population because of the possibility of germline mosaicism in one of the parents. If parental somatic mosaicism is confirmed (found in one family so far) recurrence risk may be higher, potentially up to 50%.