Temporal Lobe Malformations in Achondroplasia: Expanding the Brain Imaging Phenotype Associated withFGFR3-Related Skeletal Dysplasias

Abstract

Thanatophoric dysplasia, achondroplasia, and hypochondroplasia belong to the () group of genetic skeletal disorders. Temporal lobe abnormalities have been documented in thanatophoric dysplasia and hypochondroplasia, and in 1 case of achondroplasia. We retrospectively identified 13 children with achondroplasia who underwent MR imaging of the brain between 2002 and 2015. All children demonstrated a deep transverse temporal sulcus on MR imaging. Further common neuroimaging findings were incomplete hippocampal rotation (12 children), oversulcation of the mesial temporal lobe (11 children), loss of gray-white matter differentiation of the mesial temporal lobe (5 children), and a triangular shape of the temporal horn (6 children). These appearances are very similar to those described in hypochondroplasia, strengthening the association of temporal lobe malformations in -associated skeletal dysplasias.

Definitions and classification of malformations of cortical development: practical guidelines

“…8 ). Moreover, there may be primary forms due to genetic conditions such as FGFR3 ( Manikkam et al , 2018 ) and FGFR2 mutations ( Stark et al , 2015 ) as well as tubulin mutations ( Oegema et al , 2015 ; Mutch et al , 2016 ; Romaniello et al , 2018 ) ( Fig. 8A–D ), or secondary forms due to distortion of the sulcation pattern from presence or absence of nearby intracranial structures [such as in the case of stenogyria due to the absence of the cerebral falx in the Chiari II malformation ( Miller et al , 2008 )], or in the case of ACTA2 mutations where the rigidity of the abnormal arteries probably leads to an abnormal conformation of the mesial hemispheric sulci ( D’Arco et al , 2018 ) ( Fig.…”

Achondroplasia: a comprehensive clinical review

“…Given that achondroplasia and hypochondroplasia belong to the same family of bone dysplasias [52], it would not be surprising to identify similar dysgenesis in occasional individuals with achondroplasia. In fact, that was recently reported by Manikkam et al [215] In neither disorder has the frequency of temporal lobe structural abnormalities been determined. Nor has the frequency with which temporal lobe dysgenesis results in seizures, or whether temporal lobe abnormalities are a marker for more severe central nervous system consequences of FGFR3 been determined.…”

“…Although far more common in those with hypochondroplasia [77], seizures occasionally arise in those with achondroplasia [214, 215]. In fact, paroxysmal events with apnea in infants with achondroplasia may arise from a variety of causes: secondary to abnormalities at the craniocervical junction and consequent abnormality of central respiratory control; from primary seizures; from airway obstruction related to macrocephaly and hypotonia (e.g.…”

Integrative genomics analysis identifies five promising genes implicated in insomnia risk based on multiple omics datasets

“…The FGFR3 gene, encoding a member of the fibroblast growth factor receptor family, has been reported to be exclusively expressed in the locus coeruleus in patients with major depressive disorder [89]. Previous studies have demonstrated that skeletal dysplasia patients with Asn540Lys mutation in the FGFR3 gene have been documented to accompany with medial temporal lobe dysgenesis and epilepsy [90][91][92].…”