Genetic counselling in Noonan syndrome

Abstract

A clinical and echocardiographic study is presented of 117 families with Noonan syndrome. The 117 families contained 144 individuals with typical Noonan syndrome. The age range of these individuals was from one week to 45 years (mean 12.0 years). One parent was definitely affected with Noonan syndrome in only 14% of the 117 families (mother 11%, father 3%). In a further 31% of families, one parent had possible signs of Noonan syndrome, based on facial appearance only. Within the apparently sporadic group of probands there was no evidence of increased parental age. Echocardiography demonstrated no cases of subclinical cardiac disease in all first degree relatives examined, and clinical examination alone missed no case of cardiac disease. Segregation analysis of affected pedigrees confirmed autosomal dominant inheritance. If both parents had only possible or no signs of Noonan syndrome, subsequent to the birth of the first child with Noonan syndrome in a family, an empiric recurrence risk of 5% was obtained.

Prenatal features of Noonan syndrome

“…Counselling parents about recurrence risks can be made difficult by the more subtle phenotype in adults (Allanson et al, 1985). Sharland et al (1993) studied 117 families of children with Noonan syndrome. One of the parents had typical Noonan syndrome in 14 per cent of families.…”

“…The recurrence risk was 5 per cent for the 86 per cent of families where the parents had only possible or no signs of Noonan syndrome. All family studies have demonstrated maternal transmission of Noonan syndrome more often than paternal transmission, possibly because of infertility related to cryptorchidism in affected males (Sharland et al, 1993).…”

“…As Noonan syndrome is inherited in an autosomal dominant manner (Sharland et al, 1993), it is important to look for features of Noonan syndrome in the parents in cases presenting with prenatal features suggestive of this syndrome. The diagnosis of Noonan syndrome in a parent would help make the diagnosis in the fetus and thus aid prenatal counselling.…”

Bases Genéticas dos Distúrbios de Crescimento

“…A síndrome de Noonan é uma síndrome bem conhecida de anormalidades congênitas múltiplas, caracterizada por alterações faciais típicas, baixa estatura, defeitos cardíacos congênitos (mais freqüentemente estenose de valva pulmonar ou cardiomiopatia hipertrófica), deformidade torácica e criptorquidia em homens (111)(112)(113)(114)(115)(116)(117)(118). Foi definida como uma entidade clínica distinta da síndrome de Turner em 1963 e pode ocorrer como uma doença esporádica ou em um padrão consistente com herança autossômica dominante (119).…”

“…A incidência estimada é de 1/1000 a 1/2500 nascidos vivos (116)(117)(118)(119). A prevalência elevada da sín-drome não sugere um rearranjo cromossômico ainda não detectado, deve-se considerar a heterogeneidade genética (120).…”