Background: Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder, which remains a clinical diagnosis. The Netchine-Harbison clinical scoring system (NH-CSS), recently adopted by the first international consensus on SRS, defines SRS with at least 4 of the 6 following criteria: born SGA, postnatal growth retardation, relative macrocephaly at birth, prominent forehead, body asymmetry and early feeding difficulties. It is related to 11p15 ICR1 loss of methylation (LOM) in about 50% of patients and to maternal uniparental disomy of chromosome 7 in 10%. The molecular etiology remains unknown in about 40%.
Objective: To clinically characterise a series of patients with molecular anomalies at the imprinted region 14q32 DLK1/GTL2 and to establish their NH-CSS.
Method: We analysed retrospectively a cohort of 24 patients: 16 with 14q32 DLK1/GTL2 LOM; 7 with maternal uniparental disomy of chromosome 14 and 1 with a paternal deletion.
Results: 75% of patients presented a NH-SCC ≥ 4/6, confirming a clinical diagnosis of SRS. Mean birth length, weight and head circumference were −2.5 SDS, −2.3 SDS and −1.4 SDS respectively. The mean height at 2 years was −2.0 SDS. Prominent forehead was identified in all patients, relative macrocephaly in 54% and body asymmetry in 33%. Early feeding difficulties were noted in 79% and the mean body mass index at 2 years was −1.5 SDS. Additional clinical signs included small hands (74%), small feet (59%), motor delay (62%), speech delay (53%) down turned mouth (75%), low set posteriorly rotated ears (60%). Patients who were at least 8 years old presented early (73%) or precocious (27%) puberty, after a period of BMI increase. Many patients presented an exaggerated adrenarche (high DHEAS levels for age) and 44% presented adrenarche before puberty.
Conclusion: The majority of patients with 14q32 DLK1/GTL2 disruption fulfilled the clinical criteria for SRS. The clinical overlap with patients with 11p15 ICR1 LOM remains to be explained in terms of molecular mechanisms.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology