A case of a rare disease in a newborn child. Costello syndrome: causes, symptoms and treatment Costello syndrome description

Costello syndrome (South Carolina) is a rare genetic disorder that is defined by the presence of various developmental disorders and multiple physical malformations (Martínez-Glez and Lapunzina, 2016).

Clinically, it is characterized by: generalized intrauterine and postnatal physical growth retardation, atypical facial configuration, significant psychomotor retardation, cardiac changes, endocrine abnormalities, ectodermal and skeletal changes and a high susceptibility to the development of tumors (Martínez-Glez and Lapunzina, 2016).

Those affected may have various cognitive impairments and/or various intellectual developmental disabilities. However, a characteristic feature of Costello syndrome is the high degree of sociability of people who suffer from it (Maldonado Martinez, Torres Molina, and Duran Lobaina, 2016).

At the etiological level, it represents an autosomal recessive pattern associated with specific mutations in a gene located on chromosome 11 (Hernández-Martín and Torrelo, 2011).

Given the wide range of signs and symptoms that define the clinical course of Costello syndrome, its diagnosis requires an interdisciplinary approach. Physical, neurological, cardiological, etc. are fundamental.

In addition, treatment will be individualized to control specific medical complications. The most common is that it includes pharmacological, surgical and rehabilitation treatments.

Characteristics of Costello syndrome

Costello syndrome is a disease of congenital genetic origin that causes a broad pattern of organic involvement (Genetics Home Reference, 2016).

It is typically defined by disturbances in physical growth and cognitive development, craniofacial changes, and other types of developmental defects (Genetics Home Reference, 2016).

The most common ones tend to affect the heart or musculoskeletal structure (Genetics Home Reference, 2016).

It is also a medical condition characterized by the systematic development of tumor formations (National Organization for Rare Disorders, 2016).

Various authors, such as Martínez-Glez and Lapunzina (2016), indicate that Costello syndrome is part of the disorders that represent a genetic and/or hereditary predisposition to cancer and neoplastic processes.

It shares many characteristics with other types of diseases such as Noonan syndrome or cardiofacial syndrome (Genetics Home Reference, 2016).

They all share common features, making differential diagnosis costly early in life (Genetics Home Reference, 2016).

The first descriptions of this syndrome are between 1971 and 1977 (Proud, 2016).

In his first medical reports, Costello referred to some of the most characteristic features of this syndrome (Proud, 2016).

He described two patients whose clinical course was characterized by the presence of abnormally high birth weight, significant feeding problems, coarse facial configuration, firm and hyperpigmented skin, cognitive deficits, and a “humorous” personality (Maldonado Martinez, Torres Molina, and Durán Lobaina, 2016 ).

In early experimental studies, Costello syndrome was considered a rare disease. Its characteristics were mainly associated with physical and mental retardation (Maldonado Martinez, Torres Molina, and Durán Lobaina, 2016).

However, specific etiological characteristics were defined in 2005 (Hernández-Martín and Torrelo, 2011).

statistics

Costello syndrome is classified as a rare or uncommon disorder. Rare diseases are defined by their low prevalence in the general population (Rare Disease Day, 2016).

Although exact numbers vary between countries, they are estimated to have a lower prevalence (1 case in 200,000 people, Rare Disease Day 2016).

Epidemiological analysis and clinical reports indicate that there are no more than 200 or 300 cases of Costello syndrome worldwide (Genectics Home Reference, 2016).

Its prevalence is estimated to range from 1 in 300,000 people/1.25 million people (Genectics Home Reference, 2016).

Signs and symptoms

As we have already noted, Costello syndrome is characterized by a broad pathology of multisystem involvement.

The Multimorphic Genetic Syndromes Cancer Working Group (2016) points out some of the most common among affected individuals:

Generalized growth retardation

• Macrosomia of newborns: At the time of birth, those affected tend to weigh more than expected. This medical condition usually has important consequences in the subsequent development of childhood obesity or diabetes.
• Low size: The height of people affected by this syndrome usually does not reach the expected average for their age group and gender in the later stages of development. In most cases it is a product of poor nutrition.
• Feeding problems: Feeding is often significantly disrupted due to noticeable difficulties in sucking and swallowing.
• Delayed bone age: the bone structure develops parallel to the rest of the body. There are several milestones that can be related to a person's biological age. Costello syndrome reveals immature bones that are poorly developed for the patient's age.

Neurological changes

• Chiari malformation: Malformations in the cerebellum and brainstem areas can cause displacement of other structures, mechanical pressure, blockage of blood flow, etc.
• Disrtria: Maxillary abnormalities and neurological damage can cause changes in the production and articulation of speech sounds.
• Polihidromnios When the embryo during the pregnancy phase ingests amniotic fluid, which protects it from the external environment, it may suffer from gastrointestinal disorders, anencephaly, miotic dystrophy, achondroplasia or Beckwith syndrome.
• Hydrocephalus: Abnormal and pathological accumulation of cerebrospinal fluid can be found in several areas of the brain. This medical condition can cause expansion or destruction of various nerve structures. Symptoms tend to vary, although the most common are confusion, drowsiness, headache, blurred vision, seizures, etc.
• Cramps: Episodes of motor agitation, muscle spasms, loss of consciousness, or abnormal sensations may occur due to disorganized neuronal activity.
• Intellectual disability: Having cognitive changes and different intellectual levels is common among.

Craniofacial disorders

• Macrocephaly: The overall structure of the head is usually represented by an abnormally large size. The perimeter of the skull usually exceeds the average values ​​expected for the age and sex of the patient.
• Facia's melancholy: Facial features are usually very emphasized. The structures that make up the face are usually larger than normal. In addition, they are accompanied by various developmental defects.
• Depressed nasal bridge: The midline of the nose usually has a flat and recessed configuration.
• Anteverted Narinas: The nostrils represent a changed position. They are located in the direction of the frontal plane.
• Short nose: The overall structure of the nose is usually small, with little development at the front.
• Thick eyebrows: The eyebrows take on a rough configuration and are presented in a wide and densely populated structure.
• Pstosis: The eyes and eye sockets may be further apart than expected. On a visual level we see very separated eyes.
• nystagmus: The eyes may present involuntary, repetitive, spasmodic and asynchronous movements.
• Epic folds: Wrinkles or excess skin may appear on the terminals of the upper eyelids.
• strabismus: One eye may be deviated from the plane or line of sight. The most common is to observe the eye turned inward or outward from the midline of the face.
• Long mouth: Both the mouth and lips are usually large in size. They show a wider structure than usual.
• Gingival hyperplasia: Your gums are swollen or larger than usual. This can affect the entire oral structure or specific areas of the gums.
• Poor dental occlusion Due to craniofacial malformations, teeth are typically displaced and unstructured. They usually make feeding difficult.
• Ogival sky the palate or roof of the mouth sounds very narrow. This pathology interferes with the development and placement of the tongue and the growth of teeth.
• Low implantation ears: The ears are usually in a lower position than normal.
• Large pavilion headphones: The global structures of the ears should be overdeveloped, showing increased size.
• dysphonia It is likely that many victims have a hoarse or very serious voice. In many cases they are associated with vocal cord abnormalities.

Musculoskeletal manifestations

• Short neck: The neck structure does not develop normally. Representation of a reduced distance between the torso and head.
• Muscular hypotonia: The presence of decreased muscle tone causes significant flaccidity in the limbs and other muscle groups.
• Distal phalanges are wide The bone structure of the fingers and toes is usually wide. In addition, hyperextension in the fingers may be observed.
• scoliosis: The bony structure of the spine may have an abnormal curvature or deviation.
• Shortening of the Achilles tendon: The tendon located at the back of the ankle is not long enough, causing pain and mobility problems.

Epithelial changes

• Hypoplastic nails: fingernails and toenails are almost not formed. Very fine structure and abnormal texture usually appear.
• Hyperpigmented skin: The presence of spots on the skin is another of the central features of this syndrome. They usually have a dark, easily recognizable color.
• Redness of the skin on the arms and legs: Excess skin can be seen in different areas of the body, especially the arms and legs.
• papillomas: It is possible to identify benign tumors in areas around the mouth. They are usually small and asymptomatic.
• Curly hair: hair usually shows abnormal or sparse distribution in some areas. The most common is that those affected have curly hair.

Cardiac abnormalities

• dysrhythmia: It is possible to detect a significant change in heart rate.
• Congenital heart defects: variable presence of aortic stenosis, interauricular or interventricular communication, among others.
• Hypertrophic cardiomyopathy thickening of the cardiac myocardium is observed, which causes circulatory and blood pumping problems.

Tumor formations

Another cardinal feature of Costello syndrome is the appearance of tumor, benign and malignant processes.

Some of the most common tumors in this disease are neuroblastomas, radbomyosarcoma, and bladder cancer.

reasons

The cause of Costello syndrome is genetic and is associated with a specific mutation on chromosome 11 at 12p15.5 (Hernández-Martín and Torrelo, 2011).

The presence of hereditary factors or a de novo mutation in the HRAS gene is responsible for the clinical course characteristic of this disease (Genetics Home Reference, 2016).

The HARAS gene is responsible for creating various biochemical instructions for the production of a protein called H-RAS, with a fundamental role in cell growth and division (Genetics Home Reference, 2016).

diagnostics

The diagnosis of Costello syndrome involves a broad multidisciplinary medical evaluation:

• Medical history.
• Physical examination.
• Neurological examination.
• Cardiac examination.

In general, the coordinated work of numerous specialists and laboratory tests are required: computed tomography, magnetic resonance, conventional radiographs, skin biopsy, cardiac ultrasound, etc.

In addition, genetic studies are important to identify specific mutations and heritability.

treatment

Treatment for Costello syndrome aims to control symptoms and specific medical complications associated with each area.

As with diagnosis, medical intervention requires the participation of various specialists: cardiologists, orthopedists, dermatologists, ophthalmologists, speech therapists, nutritionists, neuropsychologists, etc.

There is no therapeutic protocol designed specifically for this syndrome. All interventions vary significantly among survivors.

In addition to purely physical, pharmacological and surgical treatment, people suffering from Costello syndrome may greatly benefit from special educational programs, psychological therapy, early stimulation, occupational therapy and neuropsychological rehabilitation.

links

1. Hernandez-Martin, A., and Torrelo, A. (2011). Rasopathies: developmental disorders with a predisposition to cancer and skin manifestations. Actas Dermosifiliogr. Retrieved from Actas Dermosifiliogr.
2. Maldonado Martínez, Y., TorresMolina, A., & Duran Lobaina, D. (2016). Costello syndrome. Presentation of the case. Medisur.
3. Martinez-Glez, V. & Lapunzina, P. (2016). Costello syndrome. Working Group on Cancer and Polymorphic Genetic Syndromes.
4. NIH. (2016). Costello syndrome. Retrieved from Genetics Home Reference.
5. NORD. (2016). Costello syndrome. Retrieved from the National Organization for Rare Disorders.
6. Proud, V. (2016). A Guide to Costello Diastolic Syndrome. International Costello Syndrome Support Group.

Description

Determination method Sequencing

Study of HRAS gene mutations.

Type of inheritance.

Autosomal dominant. Most cases are sporadic. Gonadal mosaicism is possible.

Genes responsible for the development of the disease.

The V-HA-RAS HARVEY RAT SARCOMA VIRAL ONCOGENE HOMOLOG gene is located on chromosome 11 in region 11p15.5. Contains 6 exons.

Mutations in this gene also lead to the development of congenital myopathy with excess spindle-shaped muscle fibers, Schimmelpenning-Fuerstein-Mims syndrome; somatic mutations predisposing to blood cancer, seborrheic nevus, follicular thyroid cancer.

Definition of disease.

A rare disease characterized by multiple congenital anomalies: postnatal growth retardation, coarse facial features, skin changes, diffuse hypotension and cardiac pathology (hypertrophic cardiomyopathy, congenital heart defects, arrhythmia). There is a predisposition to the development of tumors.

Pathogenesis and clinical picture.

The HRAS gene belongs to the group of RAS oncogenes, the proteins of which are GDP/GTP binding proteins involved in intracellular signal transduction.

Clinical manifestations of Costello syndrome: dermatological - the presence of excess skin on the neck, palms, soles of the feet (with hyperkeratosis of the palms and soles and thickening of loose skin of the hands and feet), acanthosis nigricans, dark skin, papillomas; lack of active development in the first months after birth leads to short stature, despite normal weight gain in later life; cardiomyopathy is a common symptom, but other forms of visceral pathology are rare; hyperextensibility of the fingers and toes is common; There is a mild to moderate intellectual deficit, and most patients are sociable and friendly.

According to clinical manifestations, Costello syndrome largely overlaps with Noonan syndrome.

In the neonatal period, attention is drawn to relative macrocephaly, a characteristic face with a large mouth, thick lips, excessive folding of the skin, a wide bridge of the nose, a large forehead, and epicanthus. The most striking clinical symptom is dysphagia (95% of children). At the same time, appetite and sucking reflex are preserved. It should be noted deep folding of the skin on the palms and soles, palmoplantar hyperkeratosis, hyperpigmentation of the skin in natural folds, along the midline of the abdomen, hyperpigmentation of the nipple areolas. Papillomas often occur around the mouth, in the vestibule of the nose and perianal. In 50% of cases, various hernias are detected. Severe hypotension, a sharp delay in physical, motor and neuropsychic development, anxiety, and irritability are noteworthy. Already in the first year of life, signs of pulmonary valve stenosis, hypertrophic cardiomyopathy, and supraventricular tachycardia may appear. Hydrocephalus may develop, and attacks of epilepsy have been described.

They are distinguished by their sociability, friendliness, and have a certain sense of humor. However, intellectual deficiency becomes apparent.

Adolescents with Costello syndrome have classic facial features, curly hair, nasal fibromatosis, pectoral papillomas, hyperkeratosis, hyperpigmentation, short stature, orthopedic disorders (tight heel tendon and foot deformities), and mental retardation. Delayed or disordered puberty is observed. Due to increasing kyphoscoliosis, sparse hair and aging skin, patients look older than their age. High risk of malignant neoplasms.

Frequency of occurrence: 1:1,000,000.

A list of mutations studied can be provided upon request.

Literature

1. OMIM.

Preparation

No special preparation is required for the study.

Literature

1. Kozlova S.I., Demikova N.S. Hereditary syndromes and medical genetic counseling. – M.: KMK, 2007 – 448 p.
2. Kenneth L. Jones “Hereditary syndromes according to David Smith” Atlas-reference book. Moscow, Praktika, 2011.
3. Costello, J. M. Costello syndrome: update on the original cases and commentary. (Letter)Am. J. Med. Genet. 62: 199-201, 1996.
4. OMIM.

Indications

Typical clinical picture: short stature, excess skin on the neck, hands and feet, curly hair, distinctive face, mental retardation.

Who should be examined if a mutation is detected: if a child is identified - both parents, brothers and sisters.

Literature

1. Kozlova S.I., Demikova N.S. Hereditary syndromes and medical genetic counseling. – M.: KMK, 2007 – 448 p.
2. Kenneth L. Jones “Hereditary syndromes according to David Smith” Atlas-reference book. Moscow, Praktika, 2011.
3. Costello, J. M. Costello syndrome: update on the original cases and commentary. (Letter)Am. J. Med. Genet. 62: 199-201, 1996.
4. OMIM.

Interpretation of results

Interpretation of study results contains information for the attending physician and is not a diagnosis. The information in this section should not be used for self-diagnosis or self-treatment. The doctor makes an accurate diagnosis using both the results of this examination and the necessary information from other sources: medical history, results of other examinations, etc.

Differential diagnosis: leprechaunism.

Research result:

1. No mutation detected.
2. The mutation was detected in a heterozygous state.
3. The mutation was detected in a homozygous state.
4. The mutation was detected in the compound heterozygous state.

Literature

1. Kozlova S.I., Demikova N.S. Hereditary syndromes and medical genetic counseling. – M.: KMK, 2007 – 448 p.
2. Kenneth L. Jones “Hereditary syndromes according to David Smith” Atlas-reference book. Moscow, Praktika, 2011.
3. Costello, J. M. Costello syndrome: update on the original cases and commentary. (Letter)Am. J. Med. Genet. 62: 199-201, 1996.
4. OMIM.

Synonym for Costello-Dent syndrome. Pseudo-pseudohypoparathyroidism.

Definition. A disease characterized by the simultaneous presence of manifestations of both hypo- and.

Symptomatology of Costello-Dent syndrome:
1. Clinical picture of hyperparathyroidism with generalized fibrous osteitis (S. Engel-v. Recklinghausen).
2. Blood biochemistry: hypocalcemia, hyperphosphatemia, significantly increased alkaline phosphatase activity.
3. Hypocalciuria (differential diagnostic sign).
4. Tetan-like convulsions and other manifestations similar to tetany syndrome.
5. Absence of dwarf stature (differential diagnostic sign), normal renal function (differential diagnostic sign).

Etiology and pathogenesis of Costello-Dent syndrome. Unknown. Based on their observations, Costello and Dent suggest that the parathyroid gland produces two different hormones. The first of them regulates the content of calcium and phosphorus in the blood; the second causes the development of fibrous osteitis, and also contributes to an increase in the activity of alkaline phosphase.

In this syndrome, the first hormone is absent or its content is reduced, and the second functions redundantly. There are other interpretations of the possible pathogenesis of suffering.

Differential diagnosis of Costello-Dent syndrome. Brachymetacarpal dwarfism syndrome. S. Engel-v. Recklinghausen (see). S. Martin-Albright (see). Tetany. S. Jaffe-Lichtenstein (see). S. Rathbun.

Diagnosis of rare hereditary diseases in children caused by mutations in structural genes still seems quite complex and is based on characteristic clinical and phenotypic signs. The article presents a clinical case of diagnosing a rare hereditary disease in a newborn child - Costello syndrome.

The case of rare diseases at the newborn child

Diagnosis of rare genetic disorders in children, caused by mutations in the structural genes, up to date is rather complex and based on characteristic clinical and phenotypic characteristics. The article presents a case of diagnosis of a rare hereditary disease of the newborn child - Costello syndrome.

In the last decade, high-tech diagnostic methods have been actively introduced into medical practice, but most hereditary syndromes are diagnosed primarily on the basis of a characteristic clinical picture. One such disease is Costello syndrome. This rare genetic disorder was first described in 1977 by Dr. Jack Costello from New Zealand. Its occurrence is 1 in 24 million people. Currently, about 300 patients with this syndrome are registered. The occurrence of the disease is associated with a mutation of the HRAS gene on the short arm of chromosome 15 (11p15.5), which is localized at codons 12 or 13. This gene encodes the synthesis of the overactive HRAS protein, which causes continuous overactive cell division and cell growth. The disease is inherited in an autosomal dominant manner. A significant proportion of probands have spontaneous mutations, and sporadic cases of the disease occur. Men and women suffer equally. Patients with Costello syndrome are usually infertile.

Since the features of the fetal phenotype are nonspecific and the syndrome is rare, the question of prenatal diagnosis does not arise. However, ultrasound examination reveals polyhydramnios in 90% of cases; brachycephaly and shortening of the humerus and femur can be seen in the fetus.

Costello syndrome is diagnosed clinically. Formal diagnostic criteria for Costello syndrome have not yet been developed, but the main unique symptoms of the disease make patients recognizable at any age.

The newborn period is characterized by relative macrocephaly, a characteristic face with a large mouth, a wide bridge of the nose, a large forehead, and excessive folding of the skin. The main clinical symptom at this age is dysphagia (95% of children) with preserved appetite and sucking reflex. Feeding problems require the use of a nasogastric tube and, in some cases, a gastrostomy tube. Commonly encountered signs include deep folding of the skin on the palms and soles, hyperpigmentation in natural folds along the midline of the abdomen, and a halo around the nipples. Changes in the cardiovascular system occur in 87% of children with Costello syndrome and are characterized by various forms of atrial tachycardia, hypertrophic cardiomyopathy is typical. Congenital heart defects occur in 44%. The most common form of the defect is non-progressive pulmonary valve stenosis. Cardiac disorders are most often present in infancy or early childhood, but can be diagnosed at any age. In 50% of cases, various hernias and the formation of papillomas around the mouth and nose can be detected. Papillomas that are absent in infancy may appear in young children; 15% of patients have a risk of malignant neoplasms. In children aged 8-10 years, neuroblastomas and rhabdomyosarcomas are more often registered, in adolescents - transitional cell carcinoma of the bladder. . Children aged 4-12 years have orthopedic problems (kyphoscoliosis, hypermobility in the joints, torticollis, “tight heel tendon”).

Severe hypotension, postnatal growth retardation, and irritability are noteworthy. Mental retardation is present in all patients. Children with Costello syndrome are distinguished by their sociability and friendliness. Adolescents experience delayed or disordered puberty. Due to increasing kyphoscoliosis, aging skin and sparse hair, patients look older than their age.

Treatment of the disease is nonspecific. In the neonatal period, it is associated with ensuring adequate nutrition; cognitive functions improve under the influence of energy-tropic therapy and early individual educational behavioral programs. Children with cardiac problems are observed and treated by a cardiologist according to existing standards.

We present our own case of clinical diagnosis of a child with Costello syndrome.

Girl S. was admitted to the neonatal pathology department of the Children's Republican Clinical Hospital in Kazan from the maternity ward at the age of 9 days due to difficulty feeding and the presence of multiple stigmata of disembryogenesis to establish a diagnosis. She was born from the 2nd pregnancy, which proceeded without complications. The child's parents consider themselves healthy. The mother is 26 years old, the father is 32 years old, and has no occupational hazards. 2nd birth at 40 weeks, total duration 4 hours 20 minutes. During labor, polyhydramnios was noted, and the amniotic fluid was light. The Apgar score at birth was 8-8 points, weight – 3000 grams, length 50 cm, head circumference 34 cm.

Upon admission, the child’s condition was assessed as serious; weight loss in the maternity hospital was 14% and was equal to 2585 grams at the time of hospitalization. From birth, the child had pronounced hyperfolding of the skin of the upper and lower extremities, hypertrichosis of the shoulders and hips, back, buttocks, hypertelorism of the palpebral fissures, large forehead, large mouth with a transverse cleft, pigmentation in the natural folds of the skin, hypertrophy of the clitoris. On the part of neuro-reflex activity, mild diffuse muscle hypotonia was detected, reflexes were evoked with exhaustion, and spontaneous motor activity was moderate. The dimensions of the large fontanel are 3x3 cm. Sucking was difficult due to macrostomia. Breathing was puerile, heart sounds were of sufficient sonority, a soft systolic murmur was detected along the left edge of the sternum, heart rate was 136-140 per minute. The abdomen was soft, the liver was palpable at 1 cm of the right edge of the costal arch, the spleen was not palpable. The stool was regular. The girl was consulted by an endocrinologist to determine the levels of glycemia, 17-OH progesterone, Na/K ratio, cortisol, TSH, and thyroxine levels. All studied biochemical constants were within physiologically acceptable values; no endocrine pathology was detected. Karyotyping determined the normal karyotype of the girl, 46, XX. An additional ultrasound examination revealed signs of hypoxic-ischemic brain damage with dilation of the left lateral ventricle to 4.5 mm, periventricular hemorrhage of the 1st degree on the left, fissure pyelectasia of the right kidney, the liver and spleen were not changed, an inflection was detected in the neck of the gallbladder. ECHO-CS with Doppler sonography determined a patent foramen ovale of 3.6 mm, grade 2-3 tricuspid regurgitation with pulmonary hypertension, and mild pulmonary artery stenosis. Based on the study, a clinical diagnosis was established: cerebral ischemia of the 2nd degree, PVK of the 1st degree on the left, syndrome of vegetative-visceral dysfunctions. Transient cardiopathy, NK0. Mild pulmonary artery stenosis, LLC, PDA in the stage of closure. The child was treated: feeding through a tube with the Nestozhen mixture every 2.5 hours, digested the food, no regurgitation was noted, parenterally received vitamin B6, piracetam, cytoflavin, infusion therapy - a glucose solution with electrolytes, and protein supplementation with amino acids. The child was consulted by a geneticist, based on clinical data of the characteristic phenotype, was malformation syndrome, Costello syndrome suspected? The presence of the main diagnostic signs - dysphagia, hyperfolding of the skin, characteristic facial features, damage to the cardiovascular system with pulmonary artery stenosis, emerging hydrocephalic syndrome - allowed us to confirm the presumptive diagnosis. The girl was discharged after 12 days with improvement, at the age of 21 days of life with a body weight of 2925 (+340 g) on ​​tube feeding with milk formula, under the supervision of a local pediatrician, neurologist, geneticist, and cardiologist. During dynamic observation at the age of 6 months, the child still has difficulty swallowing formula and anxiety when feeding with a pacifier. He is fed through a tube with 140 ml of adapted milk formula, body weight is 6630 grams, length 63 cm, head circumference 42.5 cm. Hirsutism, hyperpigmentation on the face, hypoplasia of the genital organs, excessive folding of the skin on the extremities, systolic murmur along the left edge of the sternum persist. There is a delay in psychomotor development. The child does not roll over or sit (Fig. 1, 2).

Figure 1. Face of a child with Castello syndrome

Figure 2. Hirsutism and skin folding in a child with Castello syndrome

A control ultrasound examination noted dilation of the 3rd ventricle to 6.5 mm, dilatation of the left lateral ventricle to 11.8 mm, decreased differentiation of the cortex and medulla of both kidneys, and persistent fissure pyelectasis of the right kidney. On ECHO-CS, pulmonary artery stenosis, grade 2-3 tricuspid regurgitation with pulmonary hypertension remains. Adequate feeding of the child in the first half of the year made it possible to maintain normative increases in body weight, but subsequently there may be a lag in physical development due to persistent dysphagia.

In the domestic literature there is only one report of a patient with Costello syndrome. This case of clinical diagnosis may be of scientific and practical interest for neonatologists and pediatricians.

N.H. Gabitova, F.M. Kazakova, R.N. Khakimova

Kazan State Medical University

Children's Republican Clinical Hospital of the Ministry of Health of the Republic of Tajikistan

Gabitova Nailya Khusainovna - Candidate of Medical Sciences, Associate Professor of the Department of Hospital Pediatrics

Literature:

1. Abe Y., Aoki Y., Kuriyama S., Kawame H., Okamoto N., Kurasawa K., Ohashi H., Mizuno S., Ogata T., Kure S., Niihori T., Matsubara Y. Epidemiological features of Costello syndrome and Cardio-facio-cutaneous syndrome: findings from the first nationwide survey. Chicago, IL // International Meeting on Genetic Syndromes of the Ras/MAPK Pathway. - 2011.

2. Axelrad M.E., Glidden R., Nicholson L., Gripp K.W. Adaptive skills, cognitive, and behavioral characteristics of Costello syndrome // Am. J. Med. Genet. A. - 2004. - Vol. 128A. - P. 396-400.

3. Axelrad M.E., Nicholson L., Stabley D.L., Sol-Church K., Gripp K.W. Longitudinal assessment of cognitive characteristics in Costello syndrome // Am. J. Med. Genet. A. - 2007. - Vol. 143A. - P. 3185-93.

4. Axelrad M.E., Schwartz D.D., Katzenstein J.M., Hopkins E., Gripp K.W. Neurocognitive, adaptive, and behavioral functioning of individuals with Costello syndrome: a review // Am. J. Med. Genet. C Semin. Med. Genet. - 2011. - Vol. 157. - P. 115-22.

5. Gripp K.W. Tumor predisposition in Costello syndrome // Am. J. Med. Genet. C Semin. Med. Genet. - 2005. - Vol. 137C. - P. 72-7.

6. Gripp K.W., Lin A.E., Stabley D.L. et al. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation // Am. J. Med. Genet. - 2006. - Vol. 140A. - P. 1-7.

7. Gripp K.W., Lin A.E., Nicholson L. et al. Further delineation of the phenotype resulting from BRAF or MEKI germlinemutation helps differentiate cardio-facio-cutaneos syndrome from Costello syndrome // Am. Y.Med. Genet. - 2007. - Vol. 143A. - P. 1472-1480.

8. Gripp K.W., Hopkins E., Sol-Church K., Stabley D.L., Axelrad M.E., Doyle D., Dobyns W.B., Hudson C., Johnson J., Tenconi R., Graham G.E., Sousa A.B., Heller R., Piccione M., Corsello G., Herman G.E., Tartaglia M., Lin A.E. Phenotypic analysis of individuals with Costello syndrome due to HRAS p.G13C. //Am. J. Med. Genet. Part. A. - 2011. - Vol. 155A. - P. 706-716.

9. Kozlova S.I., Demikova N.S., Semanova E., Blinnikova O.E. Hereditary syndromes and medical genetic counseling. - M.: Praktika, 1996. - pp. 122-123.

10. Kerr B., Delrue M.-A., Sigaudy S. et al. Genotype-phenotype correlation in Costello syndrome: HRAS mutation analysis in 43 cases // J. Med. Genet. - 2006. - Vol. 43. - P. 401-405.

11. Lin A.E., O'Brien B., Demmer L.A., Almeda K.K., Blanco C.L., Glasow P.F., Berul C.I., Hamilton R., Micheil Innes A., Lauzon J.L., Sol-Church K., Gripp K.W. Prenatal features of Costello syndrome: ultrasonographic findings and atrial tachycardia // Prenat. Diagn. - 2009. - Vol. 29. - P. 682-90.

12. Lin A.E., Alexander M.E., Colan S.D., Kerr B., Rauen K.A., Noonan J., Baffa J., Hopkins E., Sol-Church K., Limongelli G., Digilio M.C., Marino B., Ines A.M., Aoki Y., Silberbach M., Del-Rue M.A., While S.M., Hamilton R.M., O'Connor W., Grossfeld P.D., Smoot L.B., Padera R.F., Gripp K.W. Clinical, pathological and molecular analyzes of cardiovascular abnormalities in Costello syndrome: A Ras/MAPK Pathway syndrome // Am. J. Med. Genet. Part A. - 2011. - Vol. 155A. - P. 486-507.

13. Vasina T.N., Zubtsova T.I. and others // Russian Bulletin of Perinatology and Pediatrics. - 2010. - No. 5.

Health problems in only one organ, such as abdominal pain or diarrhea, definitely make you feel stressed and uncomfortable. What if you experience complications from two or more problems in organs or organs of the body, like people with Costello syndrome?

What is Costello syndrome?

Costello syndrome, also known as faciocutaneoskeletal syndrome (FCS), is a rare disorder that affects multiple systems or organs at the same time. Because it affects many systems of the body, sufferers of this syndrome experience disorders that are quite complex in their physical and mental state.

What causes Costello syndrome?

The cause of the rare Costello syndrome is not yet known. However, experts suspect that it has something to do with genetic mutations.

In 2005, researchers from DuPont Children's Hospital in Delaware, USA, found that about 82.5% of people with Costello syndrome experienced mutations in the HRAS gene.

The HRAS gene is a gene that is responsible for producing a protein called H-Ras. This gene mutation causes the body's cells to continue to grow and divide, even if your body doesn't tell you to. As a result, it can cause the growth of cancerous tumors and non-cancerous diseases in the body.

To date, approximately 150 cases of Costello syndrome have been published in the medical literature around the world. That's why it is not yet clear how common this syndrome occurs or the risk factors that can cause this rare syndrome.

What are the symptoms of Costello syndrome?

Most signs of Costello syndrome do not appear immediately after the baby is born. New symptoms appear as children begin to grow and develop in the first years of life.

Typical symptoms of Costello syndrome include:

• Baby's weight is difficult to lift at birth
• Short body pose
• Skin relaxes on the neck, palms, fingers and soles of the feet
• Mental retardation
• Experiencing hyperkeratosis, which is thickening of dry skin in the arms, legs, and arms
• The finger joint is flexible, not stiff
• Growth of benign papilloma tumors around the mouth and nostrils

Additionally, people with Costello syndrome also have distinctive facial features, including:

• Enlarged head (macrohepalia)
• Ear position below normal position
• Large and thick ear leaves
• Strabismus (squint)
• Thick lips
• Wide nose

Patients with this syndrome also have hypertrophic cardiomyopathy, which is an enlarged heart that weakens the heart muscle. Abnormal heart disease causes abnormal heartbeat (arrhythmia), congenital heart defects, causing benign or malignant tumor.

Can Costello syndrome be treated?

Costello syndrome can be detected early by looking for signs and symptoms from the time the baby is born. The doctor will measure the baby's weight, height, and head circumference to detect this syndrome early on.

To further make a diagnosis, the doctor will conduct a genetic test to see the possibility of gene mutations in the child's body. If a mutation in the HRAS gene is detected, the child is at risk of developing Costello syndrome.

Basically, there is no cure or specific treatment to overcome this rare syndrome. Drug treatment is not intended to cure this disease, it only relieves existing symptoms and health problems.

For example, cardiac testing is necessary to identify heart defects or heart defects in patients. Meanwhile, physical and occupational therapy is carried out to support the growth and development of late patients from their age.

Until now, no research has shown that people with this syndrome will have a short life span. This option only arises if the patient has life-threatening heart problems, a tumor or cancer. As long as the patient's health status remains healthy without cancer, he can live and live a long life like other normal people.

Costello syndrome, a rare disease that affects several organs at once