Endocrine Abstracts

JOINT1531

Background: Silver Russell Syndrome (SRS) is a rare imprinting disorder associated with prenatal and postnatal growth restriction, relative macrocephaly, feeding difficulties, protruding forehead and asymmetry. Primary molecular causes are loss of methylation within 11p15.5 imprinting control region (H19/IGF2), [11p15LOM] and maternal uniparental disomy of chromosome 7, [upd(7)mat]. There is limited research on neurodevelopmental outcomes in SRS patients.

Objective: Determine prevalences of neurodevelopmental disorders in a large cohort of molecularly-confirmed SRS patients and compare these prevalences among the SRS diagnostic groups and US general population [genUS].

Methods: 297 subjects>2 years old were divided by SRS molecular cause (including 11p15LOMn=164, upd(7)matn=99). Questionnaires about neurodevelopmental disorder diagnoses and treatments were completed by guardian or adult self. Reported diagnoses were confirmed by a qualified specialist.

Results: Speech articulation disorder prevalence was greater in upd(7)mat group (68%) than 11p15LOM group (24%), and both prevalences were significantly greater than in genUS (9%). Childhood speech apraxia was more prevalent in upd(7)mat group (24%) compared to 11p15LOM (3%) group, and both prevalences were greater than in genUS ( 0.1%). More upd(7)mat subjects had delayed onset of speech (>18 mos) than 11p15LOM subjects (52% versus 20%). Two individuals>6 yrs were non-verbal in each molecular group. Autism spectrum disorder (ASD) was more prevalent in upd(7)mat group (28%) than both 11p15LOM group (5%) and genUS (2.8%). The male to female distribution of ASD was ~1:1 in the upd(7)mat group, compared to 4.8:1 in the 11p15LOM group and 4:1 in genUS. Attention Deficit Hyperactivity Disorder prevalence was not statistically different between upd(7)mat (29%) and 11p15LOM (16%) groups, although the upd(7)mat prevalence was significantly greater than genUS (11.4%). Prevalences of intellectual disability, (IQ<75), and learning disorders were 22% and 39%, respectively, in upd(7)mat group, significantly higher than rates observed in 11p15LOM group (2% and 7%), and genUS (2.20% and 9%). However, upd(7)mat group had a normal distribution in academic performance, compared to classmates, whereas 11p15LOM subjects were skewed with 69% performing in the top third of their classes.

Conclusion: Our study shows SRS upd(7)mat individuals are at higher risk for neurodevelopmental disorders than 11p15LOM individuals and/or genUS. Aside from speech disorders, SRS 11p15LOM individuals are overall neuro similar to genUS. Understanding the prevalence of neurodevelopmental disorders in children with SRS allows for better surveillance, diagnosis and intervention. Given the 1 in 4 chance of ASD in upd(7)mat, careful monitoring for ASD could increase opportunities for early intervention.