title: Short stature and hypoparathyroidism in a child with Kenny-Caffey syndrome type 2 due to a novel mutation inFAM111Agene.
abstract: BACKGROUND
  Hypoparathyroidism in children is a heterogeneous group with diverse genetic etiologies. To aid clinicians in the investigation and management of children with hypoparathyroidism, we describe the phenotype of a 6-year-old child with hypoparathyroidism and short stature diagnosed with Kenny-Caffey syndrome (KCS) Type 2 and the subsequent response to growth hormone (GH) treatment.
  
  
  METHODS
  The proband presented in the neonatal period with hypocalcemic seizures secondary to hypoparathyroidism. Her phenotype included small hands and feet, hypoplastic and dystrophic nails, hypoplastic mid-face and macrocrania. Postnatal growth was delayed but neurodevelopment was normal. A skeletal survey at 2 years of age was suggestive of KCS Type 2 and genetic testing revealed a novelde novoheterozygous mutation c.1622C > A (p.Ser541Tyr) inFAM111A. At 3 years and 2 months, her height was 80cms (SDS -3.86). She had normal overnight GH levels. GH therapy was commenced at a dose of 4.9 mg/m2/week for her short stature and low height velocity of 5cms/year. At the end of the first and second years of GH treatment, height velocity was 6.5cms/year and 7.2cms/year, respectively with maximal dose of 7.24 mg/m2/week.
  
  
  CONCLUSIONS
  This case highlights the phenotype and the limited response to GH in a child with genetically proven KCS type 2. Long-term registries monitoring growth outcomes following GH therapy in patients with rare genetic conditions may help guide clinical decisions regarding the use and doses of GH in these conditions.
authors.affiliation: Department of Endocrinology, Princess Margaret Hospital, Perth, Australia.|School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.
authors.forename: Mary B
authors.initials: MB
authors.lastname: Abraham
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: Telethon Kids Institute, Perth, Australia.
authors.forename: Dave
authors.initials: D
authors.lastname: Tang
authors.affiliation: Department of Endocrinology, Princess Margaret Hospital, Perth, Australia.
authors.forename: Susan M
authors.initials: SM
authors.lastname: O'Connell
authors.affiliation: School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.|Genetic Services of Western Australia, Princess Margaret Hospital and King Edward Memorial Hospital, Perth, Australia.
authors.forename: Fiona
authors.initials: F
authors.lastname: McKenzie
authors.affiliation: School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, Australia.|Department of Biochemistry, PathWest Laboratory Medicine, Perth, Australia.|Sir Charles Gairdner Hospital, Nedlands, Perth, Australia.
authors.forename: Ee Mun
authors.initials: EM
authors.lastname: Lim
authors.affiliation: Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, USA.|Division of Human Genetics and Department of Pediatrics, The Children's Hospital of Philadelphia and The Perelman School of Medicine, Philadelphia, USA.|Division of Pulmonary Medicine, The Children's Hospital of Philadelphia, Philadelphia, USA.
authors.forename: Hakon
authors.initials: H
authors.lastname: Hakonarson
authors.affiliation: Division of Human Genetics and Department of Pediatrics, The Children's Hospital of Philadelphia and The Perelman School of Medicine, Philadelphia, USA.|Division of Endocrinology and Diabetes, The Children's Hospital of Philadelphia, Philadelphia, USA.|Center for Bone Health, The Children's Hospital of Philadelphia, Philadelphia, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Levine
authors.affiliation: Department of Endocrinology, Princess Margaret Hospital, Perth, Australia.|School of Paediatrics and Child Health, The University of Western Australia, Perth, Australia.|Department of Endocrinology and Diabetes, Princess Margaret Hospital, Perth, Australia.
authors.forename: Catherine S
authors.initials: CS
authors.lastname: Choong
keywords: FAM111A gene; Genetics; Growth hormone; Hypoparathyroidism; Kenny-Caffey syndrome Type 2; Short stature