Background: Costello syndrome is a rare congenital disorder with characteristic findings involving multiple organ systems. The Costello Syndrome Family Network estimates that the birth prevalence in the United Kingdom is at least 1/500,000. So far, there has been only one affected individual reported in China.
Objective and hypotheses: Diagnose the case of autosomal dominant Costello syndrome by direct squencing of HRAS gene. Analyze the correlation between phenotype and HRAS gene mutation of Costello syndrome.
Method: Total genomic DNA was extracted from peripheral blood of the patient and her parents. The coding exons 2~5 of the HRAS gene were amplified by polymerase chain react on (PCR) and sequenced directly.
Results: The 7 years old girl was born by vaginal delivery at 35+6 weeks of gestation. Birth weight was 3.55 kg, length unknown. Severe feeding difficulty and failure to gain weight were noted during the infant term. The development milestones, mental and language development were delayed. Seizures occurred three times. Her height was 100 cm (−3SD), weight 16 kg (−3SD) and head circumference 52 cm. Her distinctive facial features were characterized by epicanthus, ptosis, low-set ears, wide nasal bridge, full lip and large mouth. Physical findings present include striking deep creases in the palms and soles, coarse skin, worsening kyphoscoliosis, sparse and curly hair. A heterozygous de-novo point mutation in HRAS showed the nucleotide substitution c.34G>A, resulting in p.Gly12Ser amino acid change.
Conclusion: The phenotype of Costello, Noonan, and CFC syndromes shows such significant overlap that a clear distinction cannot always be made on clinical criteria alone, but rather molecular testing is necessary. HRAS consists of six exons. The G12S mutation is the most common change found in Costello syndrome.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology