Elevated urine catecholamine metabolites: Indicating parameters for identification of Costello syndrome

Elevated urine catecholamine metabolites are well known indicators for pheochromocytomas and neuroblastomas with associated myoclonus opsoclonus syndrome.

We report on a 3 months old child patient of unrelated parents with failure to thrive since the first weeks of life, hyperhidrosis, tachycardia without variability of frequency and tachydyspnoea. Furtheron a cardiomyopathy developed. We suspected a disturbance in the sympathic nervous system regulation and performed an analysis of urine catecholamine metabolites which showed a concentration of vanillylmandelic acid within the upper level of the normal range. MIBG scintigraphy did not show any signs of an expected pheochromocytoma. Regarding to associated distinctive facial abnormalities, lax skin, especially in the region of hands and feet, and persistent growth retardation we suspected a Costello syndrome.

The 1987 described Costello syndrome is a rare congenital malformation syndrome. It is caused by recently discovered mutations in the HRAS gene. Until now only de novo mutations are known. Clinically the Costello syndrome consists of distinctive facial, skin and musculosceletal features, the above mentioned autonomic symptoms with development of a cardiomyopathy, furthermore cardiac dysrhythmias, postnatal growth retardation and psychomotor developmental delay. Predisposition for tumor development especially rhabdomyosarcomas is described. The symptoms will usually improve with ongoing age. Therapy of the Costello syndrome consists of symptomatical procedures. Tube feeding by gastrostomy is nearly almost mandatory. A tracheostomy could be able to improve ventilation problems in case of severe tracheal and laryngeal malacia.

In our patient we found a de novo heterozygous missense mutation c.34G→A in exon 2 of the HRAS gene. Nutrition is secured by gastrostomy tube feeding. There still exist recurrent gastrointestinal problems with vomiting, diarrhoea and meteorism. The cardiac situation could be improved dramatically by beta blocker therapy.