Costello syndrome is a rare hereditary disease, which is manifested by the characteristic features of the phenotype, multiple congenital malformations. The disease is caused by a mutation of the HRAS gene and is inherited in an autosomal dominant type. Typical signs of the syndrome are dysphagia, cardiovascular diseases, growth retardation, and psychomotor development. The plan of diagnostic measures includes molecular genetic tests, neurologist consultation, instrumental examination of the heart. For the treatment of Costello syndrome, supportive therapy is prescribed in accordance with the severity of symptoms.
Q87.8 Other specified syndromes of congenital anomalies, not classified elsewhere
The syndrome was first described in 1977 by the doctor J. Costello from New Zealand, after whom it got its name. In 1983, the molecular genetic prerequisites of pathology were established. The disease is very rare — 1 case per 24 million population, 10 children are born with this diagnosis every year. According to statistics, about 300 people with Costello syndrome now live in the world. Despite the low prevalence, the disease does not lose its relevance in modern genetics, it requires competent comprehensive rehabilitation of patients.
The syndrome is caused by a mutation of the HRAS gene located on the short arm of the 11th chromosome at the 11p13-3 locus. Today, an autosomal dominant type of gene defect transmission has been described. However, most sufferers of Costello syndrome are infertile, so it does not have much practical significance. Mutations of genetic material occur spontaneously, predisposing factors have not yet been established.
The HRAS gene encodes the formation of an overactive protein, which is necessary to stimulate the reproduction of various cells of the body. In Costello’s disease, excessive protein synthesis occurs, as a result of which continuous uncontrolled cell division begins in the tissues. Such processes not only disrupt intrauterine ontogenesis, but also cause multiple benign and malignant tumors in patients.
The disease manifests itself in the first year of a child’s life. The main manifestation of Costello syndrome at this age is considered to be a violation of swallowing, as a result of which the baby spits out or regurgitates food, experiences severe anxiety during feeding. At the same time, the sucking reflex is normal, the appetite is preserved. Lack of nutrients provokes a delay in physical and psychomotor development. Over time, there is a lag in growth.
Patients have characteristic external features. The syndrome is characterized by a rounded head shape, a wide face with a large mouth and full lips. Attention is drawn to the high forehead, wide bridge of the nose, epicanthus. Excessive skin folding is observed on the palms and soles, foci of hyperkeratosis, hyperpigmentation appears on the body, multiple papillomas. Due to the flabbiness of the skin, rare dry hair, patients look older than passport age.
About 87% of children with Costello syndrome clinic suffer from hypertrophic cardiomyopathy, supraventricular forms of tachycardia. In 44% there are congenital cardiac anomalies: defects of the atrial and interventricular septa, stenosis of the pulmonary artery valve. Neuropsychiatric disorders are manifested by mental retardation, epileptic seizures, hydrocephalus.
In children of preschool and primary school age, growth retardation is aggravated, the syndrome is complicated by multiple orthopedic disorders: deformity of the feet, “tight heel tendon”, kyphoscoliosis. About 15% of patients are confronted with malignant neoplasms. Neuroblastomas, rhabdomyosarcomas, and bladder cancer occur most often. Oncopathology is the main cause of premature death in Costello syndrome.
Patients are examined by a pediatrician (family doctor), neurologist, geneticist. Experienced doctors may suspect the disease by typical features of appearance, combined with severe dysphagia, lag in psychomotor development. To confirm or refute the diagnosis, various laboratory and instrumental research methods are prescribed:
- Genetic testing. The study of the genome for a specific gene mutation is the only way to verify the diagnosis, since no other diagnostic criteria have been developed due to the rare occurrence of Costello syndrome.
- Neurological examination. Disorders of muscle tone, swallowing reflex, intellectual development delay — indications for examination by a neurologist. In addition to physical examination, methods of electroneuromyography, EEG, CT or MRI of the brain are used.
- Ultrasound of the heart. Echocardiography is the safest method of detecting congenital heart defects in patients of any age. To clarify the parameters of blood flow, it is supplemented by Doppler ultrasound. If necessary, an extended diagnosis of cardiac manifestations of the syndrome is performed using ECG, chest x-ray, angiography.
- Prenatal diagnosis. Screening ultrasound, as a rule, determines the brachycephalic shape of the fetal head, disproportionate shortening of the proximal extremities, polyhydramnios. These signs are not specific, so a molecular genetic analysis is necessary to confirm the diagnosis.
Therapy of Costello syndrome is limited to symptomatic measures, since there is no etiotropic treatment of pathology. Patients require medical care from infancy. The treatment plan is drawn up individually, taking into account the peculiarities of the clinical picture of a particular patient. The main directions of therapy:
- Nutritional support. For adequate feeding of children in conditions of dysphagia, a nasogastric probe is used, and in severe cases, a gastrostomy or a Nissen fundoplication is required. Often, at the age of 4-6, the feeding situation normalizes.
- Neurorehabilitation. Since all patients have cognitive impairments of varying severity, they require classes with correctional teachers, speech therapists, as well as special educational programs.
- Orthopedic correction. To eliminate or minimize skeletal deformities typical of the syndrome, special complexes of physical therapy, mechanotherapy, massage are prescribed. According to the indications, therapeutic fixation and surgical interventions are recommended.
- Cardiac surgical care. Patients with congenital anomalies of the heart and main vessels are operated on in standard terms according to cardiological protocols. Most interventions are planned at the age of 1-3 years.
Prognosis and prevention
Comprehensive rehabilitation programs help to improve the intellectual development of patients, eliminate psychomotor disorders, so the prognosis is relatively favorable. The greatest danger is represented by frequent concomitant oncological diseases, severe congenital heart defects. There are no effective measures to prevent the syndrome, which is explained by the orphan nature of the disease, the ambiguity of the provoking factors.