Costello syndrome (CS) is a rare condition that presents with characteristic facies and affects multiple organ systems. It typically causes growth delay, mental impairment and failure to thrive in infants. Cardiac, neurological and musculoskeletal anomalies are also frequent.
Costello syndrome (CS) is a genetic disease inherited through an autosomal dominant pattern. It is a rare condition caused by mutations in the KRAS gene (Kirsten rat sarcoma viral oncogene homolog) that results in a number of congenital abnormalities . Cardiofaciocutaneous (CFC) syndrome has a similar genetic etiology and presents with significant phenotypical overlap with CS.
Children born with CS are usually macrosomic. In contrast, the neonatal period is characterized by failure to thrive, feeding difficulties, and eventually weight loss. Because of this, they may look marasmic and become irritable. Further challenges in infants involve hypotonia which varies in severity, nystagmus, and visual difficulties . There is also an increased incidence of pyloric stenosis . During development, there is usually mental impairment, growth retardation, as well as delayed puberty. Symptoms of CS are progressive, and older individuals may experience accelerated aging.
The clinical appearance of CS is coarse facies, which include a large mouth, low set ears, epicanthal folds, and upwards facing noses as well as macrocephaly. This is often accompanied by soft skin, fine, sparse hair, and facial warts .
Musculoskeletal complaints constitute lax joints, hip dysplasia, malformations of the hands and spine, and tight Achilles tendons in later childhood. Osteoporosis and osteopenia may be observed thereafter. Individuals with CS may also exhibit cardiac anomalies. These are a frequent feature of CS, with up to 87% of individuals with the condition reported to have cardiovascular malformations . Lesions described in the literature are pulmonary stenosis, enlargement of ventricles, cardiomyopathy, and various arrhythmias. The central nervous system is also affected, producing phenomena such as Arnold-Chiari malformation type I, hydrocephalus, tethering and formation of fluid-filled cysts in the spinal cord, as well as the occurrence of seizures. Additionally, those with CS show a predisposition to certain tumors, namely, neuroblastoma, embryonal rhabdomyosarcoma, and transitional cell carcinoma.
Costello syndrome can be diagnosed clinically, provided there are multiple features suggestive of the condition. Molecular genetic testing is carried out in order to make a definitive diagnosis. Amniocentesis may be carried out during pregnancy, to enable prenatal genetic analysis.
Moreover, before birth, ultrasound is instrumental in the diagnostic process, as there are certain features that are made visible with this technique. These entail fetal macrosomia, polyhydramnios, and macrocephaly, which may lead to the suspicion of maternal diabetes . In some cases, craniofacial abnormalities may be observable on ultrasound . It is estimated that about 40% of children with CS are delivered prematurely. Furthermore, most of these infants are born with birth weights above the 90th percentile for the average newborn. Severe forms of the disease can lead to early neonatal death  .