Intellectual disability (ID) affects 1%–3% of the population. While it has a strong genetic component, finding a genetic diagnosis remains challenging. Given the high rate of de novo events in ID, family-based sequencing may be an important tool. In 2012 Schuurs-Hoeijmakers et al., reported two children with ID and characteristic features associated with a heterozygote mutation in PACS1. We report the same mutation elucidated by whole exome sequencing (WES) in two additional children.

Patient 1 was born at term to a 30-year-old primigravida from Bangladesh. Her birth weight and length were 3–10th% and head circumference 50–75th%. ID presented in the first year of life. She had sparse hair, a high forehead, frontal bossing, hypertelorism, deep-set eyes, a broad nasal root, full lips and a  wide mouth. She had marked hypotonia, decreased muscle bulk and hyperextensible joints. WES revealed a PACS1 mutation. (NM_018026)exon4:c. C607T:p. R203W.

Patient 2 was born at term to a 34-year-old primigravida from China. Birth weight and length were 10–25th% and head circumference 25–50th%. At birth, an anoplasty was performed for an ectopic anus. A right duplex kidney and undescended testes were identified. ID presented before age one. He had a short forehead, bushy eyebrows, short nose, large mouth, uplifting earlobes, bilateral single palmar creases, widely spaced nipples and an umbilical hernia. WES revealed the same mutation.

Our two cases highlight the clinical utility of WES in helping establish a diagnosis of an unfamiliar clinical syndrome and supports the discovery of a now recognisable syndrome due to mutation in PACS1.