Thanatophoric dysplasia (TD) is a rare and uniformly fatal skeletal dysplasia caused by pathogenic variants in the fibroblast growth factor receptor 3 (FGFR3) gene, with TD type I showing characteristic radiological features and perinatal lethality. We report the case of a 26-year-old G2P1L0D1 mother with hypothyroidism whose foetus was identified on anomaly scan to have features suggestive of skeletal dysplasia. Serial ultrasonography revealed severe polyhydramnios and markedly shortened long bones. At 32+5 weeks of gestation, a male infant was delivered by emergency caesarean section and presented with severe respiratory distress, micromelia, and dysmorphic features. Radiographic evaluation demonstrated classic findings consistent with TD type I. Despite aggressive neonatal resuscitation, the infant succumbed shortly after birth. Singleton exome sequencing identified a heterozygous pathogenic FGFR3 variant (c.746C>G; p.Ser249Cys), while parental testing was negative, confirming a de novo mutation. This case underscores the importance of integrating antenatal imaging with postnatal genetic testing for accurate diagnosis and appropriate genetic counselling. Written informed consent for publication of clinical details and images was obtained from the parents.
Bazar et al. (Wed,) studied this question.