Background: Children with 17p13.3 microdeletions including the YWHAE gene show intrauterine growth restriction, craniofacial dysmorphisms, postnatal growth failure, and cognitive impairment. This region is characterized by genomic instability and has been associated with isolated lissencephaly sequence and Miller-Dieker syndrome characterized by facial dysmorphisms, microcephaly, short stature, seizures, cardiac malformations, and agyria. Whilst brain abnormalities are secondary to YWHAE deficiency, the cause of pre- and postnatal growth failure has not been identified yet.
Case presentation: We describe 2 patients (patient 1 15 years and patient 2 11 years and 10 months) referred to our Center of Pediatric Endocrinology for intrauterine growth retardation with de novo 17p13.3 deletion. In vitro assays showed a defect in CRK expression and GH/IGF1 signaling. rhGH therapy was effective in partially reducing the deficit in height in patient 1 and induced catch-up growth in patient 2.
Conclusion: Our results suggest that 17p13.3 microdeletion involving CRK affects both GH and IGF1 signaling ultimately leading to pre- and postnatal growth retardation, secondary to partial insensitivity to GH/IGF1. rhGH therapy may be considered to reduce the height deficit in these patients, though data on adult height are lacking.
Keywords: CRK; GH-IGF1 axis; Growth hormone therapy; SGA.
© 2021 S. Karger AG, Basel.