Radiographic and genetic diagnosis of sporadic hypochondroplasia early in the neonatal period

Abstract

Hypochondroplasia is an autosomal dominant skeletal dysplasia expressing postnatal onset of short stature with mild rhizomelic shortening of the limbs. This manifestation leads to restricted prenatal diagnosis of the disorder. We report here on a sporadic case of a hypochondroplastic baby, whose prenatal sonographic measurements were serially recorded from 19 weeks of gestation. Mild shortening of the limbs became manifest after 26 weeks of gestation. Biparietal diameter was within the normal range throughout gestation. Both parents were of average stature. A tentative diagnosis of a nonlethal short-limb skeletal dysplasia was made. At birth, the clinical manifestations of the neonate were not characteristic, but the radiographic features raised the possibility of hypochondroplasia. Molecular analyses revealed a C to G mutation at nucleotide 1659 of the fibroblast growth factor receptor 3 (FGFR3) gene, a common mutation in hypochondroplasia.

Prenatal Diagnosis of Hypochondroplasia: Three-Dimensional Multislice Computed Tomography Findings and Molecular Analysis

“…Therefore, head measurements (biparietal diameter and head circumference) remained normal in the cases reported by Jones et al [12] and Huggins et al [13] but Kataoka et al [14] described a case of rhizomelic shortness of the long bones (femur and humerus) with macrocephaly, similar to our case report. The fi nal diagnosis in this case was made postnatally by molecular analyses [12][13][14] . 3D prenatal ultrasonography has been previously evaluated in cases of skeletal dysplasia and revealed additional information about the fetal face and the spine (determination of the interpediculate distance, measurement of the height of the vertebral bodies) [15,16] .…”

“…Serial prenatal sonographic measurement of hypochondroplasic fetus was reported in the literature [12][13][14] and all described that shortening of the long bones became evident after 25 weeks of gestation and thereafter the shortening was exacerbated as pregnancy advanced. Therefore, head measurements (biparietal diameter and head circumference) remained normal in the cases reported by Jones et al [12] and Huggins et al [13] but Kataoka et al [14] described a case of rhizomelic shortness of the long bones (femur and humerus) with macrocephaly, similar to our case report. The fi nal diagnosis in this case was made postnatally by molecular analyses [12][13][14] .…”

Prenatal diagnosis of hypochondroplasia: Report of two cases

“…This discrepancy between the gestational ages as estimated by the FL and by other fetal biometric parameters such as BPD, HC, and AC, was consistent in all the reported fetuses. The remarkable deviation of the fetal growth curve of FL from the normal values in conjunction with a normal growth curve of BPD has been suggested to be a useful U/S indication for prenatal HCH diagnosis [Kataoka et al, 2004], especially when fetal karyotype is normal [Ville et al, 1998]. Abnormal central nervous system structure, presented with a slight increase in the size of the anterior horns of the cerebral ventricles has been reported only in one fetus [Huggins et al, 1999].…”

“…HCH has been detected by prenatal routine U/S examination in two sporadic cases referred initially for a non-specific short-limb skeletal dysplasia [Jones et al, 1990;Kataoka et al, 2004]. The specific diagnosis was based on clinical findings, and on the postnatally detection of the N540K FGFR3 mutation, respectively.…”

Prenatal diagnosis of skeletal dysplasia due to FGFR3 gene mutations: a 9-year experience

“…The prenatal sonographic detection of HCH is the most difficult due to the absence of specific US markers because many of the subtle symptoms of the disease are not present in utero and infancy [21]. The remarkable deviation of the foetal growth curve of femur length from the normal values in conjunction with a normal growth curve of biparietal diameter has been suggested to be a useful US indication for prenatal non-lethal skeletal dysplasia [28]. In those cases, prenatal diagnosis relies first a karyotype and later on an ACH/HCH molecular study.…”