Abstract
Pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene are responsible for a broad spectrum of skeletal dysplasias, including achondroplasia (ACH). The classic phenotype of ACH is caused by two highly prevalent mutations, c.1138G > A and c.1138G > C (p.Gly380Arg). In the homozygous state, these variant results in a severe skeletal dysplasia, neurologic deficits, and early demise from respiratory insufficiency. Although homozygous biallelic mutations have been reported in patients with ACH in combination with hypochondroplasia or other dominant skeletal dysplasias, thus far, no cases of heterozygous biallelic pathogenic ACH-related variants in FGFR3 have been reported. We describe a novel phenotype of an infant with two ACH-related mutations in FGFR3, p.Gly380Arg and p.Ser344Cys. Discordant features from classic ACH include atypical radiographic findings, severe obstructive sleep apnea, and focal, migrating seizures. We also report the long-term clinical course of her father, who harbors the p.Ser344Cys mutation that has only been reported once previously in a Japanese patient. The phenotype of heterozygous biallelic mutations in FGFR3 associated with ACH is variable, underscoring the importance of recogniti...Continue Reading
References
Sep 1, 1978·The Journal of Pediatrics·W A HortonJ G Hall
Nov 1, 1992·Journal of Medical Genetics·I D YoungN Rutter
Nov 1, 1990·American Journal of Medical Genetics·R StanescuP Maroteaux
Apr 1, 1987·American Journal of Medical Genetics·A SommerT Frye
Mar 1, 1995·Nature Genetics·P L TavorminaJ J Wasmuth
Jul 29, 1994·Cell·R ShiangJ J Wasmuth
Sep 15, 1994·Nature·F RousseauA Munnich
May 3, 1996·American Journal of Medical Genetics·J BonaventureP Maroteaux
Mar 20, 1997·Nature·W C SuX Y Fu
Mar 3, 1999·American Journal of Human Genetics·P L TavorminaC A Francomano
Jun 11, 1999·Genes & Development·M SahniC Basilico
Dec 18, 2001·American Journal of Medical Genetics·S UngerD H Cohn
Aug 19, 2003·American Journal of Medical Genetics. Part a·Maureen A Flynn, Richard M Pauli
Feb 15, 2005·Developmental Biology·Suzanne L Inglis-BroadgateTomoko Iwata
Jul 11, 2007·Journal of Child Neurology·Peter Kannu, Salim Aftimos
Sep 4, 2007·American Journal of Medical Genetics. Part a·J E Hoover-FongC I Scott
Dec 14, 2007·American Journal of Medical Genetics. Part a·Andreas ZanklTony Roscioli
Dec 25, 2009·American Journal of Medical Genetics. Part a·María Luisa Martínez-FríasUNKNOWN ECEMC Working Group
May 8, 2013·Pediatric Radiology·Cristina M PhilpottSusan Blaser
Mar 19, 2014·Pediatric Neurology·Antonino RomeoDonatella Milani
Jan 24, 2015·Molecular Genetics & Genomic Medicine·Yuan XueWilliam R Wilcox
Jul 2, 2015·American Journal of Medical Genetics. Part a·Masaki TakagiTomonobu Hasegawa
Feb 10, 2017·American Journal of Medical Genetics. Part a·Natario L CouserCynthia M Powell
May 12, 2017·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Keith NykampScott Topper