Early development of extensive acanthosis nigricans (AN) is a key feature in some patients who have hypochondroplasia (HCH) in association with FGFR3 mutations.
Recently, AN was reported in HCH with p.K650T mutation in FGFR3, and to date, there are only three reports, comprising 18 cases, describing AN harboring this specific gene mutation.
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.
Recently, gain-of-function mutations in the transmembrane domain of FGFR3 has been described associated with an aberrant negative regulation, leading to the development of achondroplasia-group disorders, including achondroplasia (ACH), hypochondroplasia (HCH) and thanatophoric dysplasia (TD).
Exome sequencing revealed that the girl was heterozygous for a missense mutation (c.1651A>G, p.Ile538Val) in exon 13 of FGFR3, a known mutation for hypochondroplasia, inherited from her mother.
Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD).
To establish radiologic criteria and scoring system for identifying neonates with fibroblast growth factor receptor 3 (FGFR3)-associated hypochondroplasia.
Mutations of the fibroblast growth factor receptor 3 (FGFR3) cause various forms of short stature, of which the least severe phenotype is hypochondroplasia, mainly characterized by disproportionate short stature.
This case represents a new expression of FGFR3 spectrum and it is of considerable importance for the genetic counseling in cases where both parents are affected with HCH.
The present case of hypochondroplasia and FGFR3 mutation in Asn540Lys associated with characteristic abnormalities involving bilaterally medial temporal lobe structures, probable hippocampal cortex focal dysplasia, and early onset of focal epilepsy underscores the possibility of a rare syndrome.