Objective: Noonan syndrome is the most common Rasopathy,
characterised by typical facial dysmorphism (hypertelorism,
downslanting palpebral fissures, ptosis, low-set posteriorly rotated
ears) and congenital heart defects. Other features include
short stature, cryptorchidism, ectodermal abnormalities, intellectual
impairment. The phenotype is variable. The disease is
caused by mutations in genes encoding proteins interacting with
the Ras-MAPK signaling pathway. How the clinical phenotype
can orient the molecular analysis will be further illustrated with
two patients. Methods: Clinical and molecular data on two patients
within the Noonan spectrum are presented. Results: The
first patient, a boy born with normal birth parameters, after
pregnancy complicated by polyhydramnios. He presented typical
dysmorphism, pectus excavatum and bilateral cryptorchidism.
Billowing of the mitral valve was seen at cardiac evaluation.
Evolution showes a relative macrocephaly and curly hair. Stature
and psychomotor development are normal. Molecular analysis of
the PTPN11 gene showed no mutations. Further analysis showed
not earlier reported mutation in the SOS1 gene (c.1670_1687del).
The second patient, a boy born with a birthweigth above the 95th
centile, presented with typical dysmorphism, macrocephaly and
atrial septal defect. Evolution shows slow growing, sparse, thin
hair, pectus excavatum and severe eczema. He has short stature
and intellectual disability. Molecular analysis of the most common
genes in the RAS-MAPK pathway didn’t reveal any mutation.
Recently a mutation was found in the SHOC2 gene (p.Ser2Gly).
Conclusion: Noonan spectrum is a genetically heterogenous disorder
but some distinctive characteristics are associated with
particular genes as illustrated in our cases. SOS1 mutations are
often associated with normal stature and normal cognition. Recently
a recurrent mutation (p.Ser2Gly)in the SHOC2 gene has
been associated with with loose anagen hair, short stature and
more pronounced intellectual impairment. Knowledge of the
phenotype–genotype correlation is helpful in clinical
Originele taal-2English
Pagina's (van-tot)S132-S132
Aantal pagina's1
TijdschriftEuropean Journal of Paediatric Neurology
Nummer van het tijdschriftMay 2015
StatusPublished - mei 2015
Evenement11th European Paediatric Neurology Society Congress 2015 - Vienna, Austria
Duur: 27 mei 201530 mei 2015
Congresnummer: 11th

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