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MG-106 Global developmental delay and characteristic facial features associated with pacs1 gene mutation – report of two cases
  1. Lauren Chad1,
  2. Brian HY Chung2,
  3. Christian R Marshall3,4,
  4. Daniele Merico3,
  5. Riyana Babul-Hirji1,
  6. D James Stavropoulos4,
  7. David Chitayat1,5
  1. 1Department of Paediatrics, Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
  2. 2Department of Pediatrics and Department of Obstetrics and Gynecology, Centre of Reproduction, Growth and Development, The University of Hong Kong, Hong Kong Special Administrative Region, China
  3. 3The Centre for Applied Genomics, The Hospital for Sick Children, Toronto, Ontario, Canada
  4. 4Department of Paediatric Laboratory Medicine, Hospital for Sick Children, Toronto, Ontario, Canada
  5. 5The Prenatal Diagnosis and Medical Genetics Program, Department of Obstetrics and Gynecology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada


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.

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