He Robinow syndrome Is a pathology of rare genetic origin that is characterized by the presence of multiple alterations and Body malformations, especially at the bone level (Genetics Home Reference, 2016).
At the clinical level, it is a disease that can affect different areas such as craniofacial structure, skeletal muscle, oral and urogenital among others (Díaz López and Lorenzo Sanz, 1996). In addition, some of the most frequent signs and symptoms in this pathology include: macrocephaly, short stature, Genital hypoplasia and atypical facial features among others.
On the other hand, regarding the etiology of Robinow syndrome, it is currently associated with the presence of specific mutations in the ROR2 genes, WNT5A, DVL1, present differentially depending on the specific heritability pattern in each case (Genetics Home Reference, 2016).
There are no specific tests or biological markers that specifically indicate the presence of Robinow's syndrome, for this reason, the Diagnosis is based on the examination of the clinical picture and the radiological study (Leon Hervert and Loa Urbina, 2013).
Robinow syndrome is present from the moment of birth, so a cure has not yet been identified, thus, the treatment is Mainly symptomatic, focuses on the control of medical complications, such as respiratory or cardiac alterations (Leon Hervert and Loa Urbina, 2013).
Characteristics of Robinow's syndrome
Robinow's syndrome is a disease of hereditary origin whose central characteristic is the generalized delay of the physical development, giving rise to The presence of reduced or reduced stature, cranioacic malformations and other musculoskeletal disorders (National Organization for Rare Disorders, 2007).
This pathology was first described in 1969 by Minhar Robinow. In his clinical report he described a series of cases characterized by Abnormal or atypical facial features, low height or hypoplastic genitalia, whose etiological origin was Autosomal dominant (Díaz López and Lorenzo Sanz, 1996).
However, subsequent studies, through the reviewed cases, pointed out that Robinow syndrome is a broadly pathological condition Heterogeneous, so that its clinical and morphological features can vary significantly through different cases.
In addition, this disease is also known as fetal facies syndrome, Robinow dwarfism, Robinow mesomelic dysplasia or acra dysotosis With facial and genital anomalies (Leon Herbert and La Urbina, 2013).
In general, the medical prognosis of Robinow syndrome is good, since life expectancy is not reduced compared to the general population, However, it presents a high index of Comorbidity , So the quality of life is significantly affected.
Frequency
Robinow's syndrome is rare worldwide and is considered a rare disease (Genetics Home Reference, 2016).
Specifically, approximately 200 cases of Robinow syndrome with an autosomal recessive hereditary origin have been described in the medical literature, While the dominant form has been identified in at least 50 families (Genetics Home Reference, 2016).
On the other hand, the incidence of Robinow's syndrome has been estimated at approximately 1-6 cases per 500,000 births each year (National Organization for Rare Disorders, 2007).
In addition, a differential frequency has not been identified in terms of sex, geographical origin or ethnic and racial groups, although, in In some cases, clinical identification is more rapid in men, due to genital abnormalities (National Organization for Rare Disorders, 2007).
Signs and symptoms
The pattern of affectation of the syndrome of Robinow is wide, since it affects of generalized form to all the corporal structure and especially to the area Craniofacial, buccal, genital and musculoskeletal.
Some of the most frequent alterations include (Díaz López and Lorenzo Sanz, 1996; Genetics Home Reference, 2016; National Organization for Rare Disorders, 2007):
Craniofacial disorders
People with Robin syndrome have a severe involvement of the cranial and facial structure, which Atypical aspect. Some of the more frequent anomalies include:
- Cranial anomalies : The most common thing is to observe a cranial volume bigger than expected for its moment of development ( Macrocephaly ), Accompanied by a prominent frontal or bulging forehead and poor or incomplete development of the lower portions of the face ( Facial hypoplasia ).
- Ocular hypertelorism : This term refers to the presence of an abnormal or excessive separation of the orbits Ocular. In addition, the development of abnormally prominent eyes with palpebral fissure inclination is common.
- Nasal anomalies : The nose usually presents a reduced or shortened structure, accompanied by a cleft nasal bridge or alterations In position.
- Structural oral anomalies : In the case of the mouth, it is frequent to observe a triangular structure, accompanied by a mandible little ( Micrognathia ).
Oral disorders
This type of alterations refers to a deficient or abnormal organization of the inner structure of the mouth and the Dental organization.
- Dental alterations : The teeth are usually misaligned, with a posterior clustering or delayed eruption of the teeth Secondary.
- Gingival hyperplasia : Both the gingiva and the rest of the tissues and soft structures of the mouth may show an enlarged appearance Or inflamed.
Musculoskeletal disorders
At the musculoskeletal level, bone involvement is one of the most significant medical symptoms in Robinnow syndrome.
- Short stature : From the gestation or the moment of the birth, it is possible to detect a delayed physical development, the bone age usually Being less than the chronological one, reason why other aspects are affected, like the stature, that is usually reduced and does not reach the standards Expected.
- Vertebral alterations : The bone structure of the spine is often poorly organized, a Underdevelopment of the vertebral bones or a fusion of some of them. In addition, the presence of scoliosis Or an abnormal curvature and Pathology of the vertebral set.
- Braquimelia : The bones that confirm the arms usually have a shortened length, so that the arms appear smaller than normal.
- Clinodactyly : A lateral deviation of some fingers occurs, especially affecting the thumb and / or the ring finger.
Urogenital disorders
Genital anomalies are also common in children with Rainbow syndrome, and are especially evident in boys.
- Genital hypoplasia : In general, the genitalia are not usually fully developed, it is Ambiguous genitals scarcely differentiated as male or female.
- Cryptorchidism : In the case of males, genital underdevelopment may cause the partial or complete absence of the The testicles towards the scrotum.
- Renal disorders : Renal function is also often affected, with Hydronephrosis (accumulation of Urine in the kidney).
Other features
In addition to the alterations detailed above, it is very common to observe the development of cardiac abnormalities and alterations. The most common are Related to obstruction of blood flow due to structural malformations.
On the other hand, in the case of the neurological area, no significant traits are usually found, since intelligence presents a standard level, just as the Cognitive functions. Only in some cases is it possible to observe a Slight delay .
Causes
Robinow's syndrome is a hereditary disease of congenital nature, and therefore has a clear genetic etiological nature.
Although different genetic components related to the clinical course of Robinow syndrome have been identified, specifically, genes ROR2, WNT5A and DVL1, the hereditary pattern is still not known with exactness, in addition it is differential is many affected (National Organization for Rare Disorders, 2007).
Specifically, cases of Robinow syndrome that are associated with specific mutations of the ROR2 gene, located on chromosome 9 (9q22), appear to To present an autosomal recessive heritability pattern (Genetics Home Reference, 2016).
In the case of genetic pathologies of recessive character, it is necessary to possess in the individual genetic material two copies of the abnormal gene or Defective, from both parents, one of each.
However, if the person only inherits one of these, it will be carrier, that is, not Will develop the clinical features of Robinow syndrome, but may transmit it to their offspring (National Organization for Rare Disorders, 2007).
Thus, in this case, the ROR2 gene has the essential function of generating the essential biochemical instructions for the production of a protein, important For normal physical development during the prenatal stage. Specifically, the ROR2 protein is critical for the formation of the bone structure Body, heart and genitals.
As a result, the presence of genetic alterations that affect the efficient function of this component, will cause the physical development to be interrupted Normalized and, therefore, the characteristic clinical features of Robinow's syndrome (Genetics Home Reference, 2016) appear.
However, the dominant forms of Robinow syndrome are associated with the presence of specific mutations in the WNT5 or DVL1 gene (Genetics Home Reference, 2016).
In the case of genetic pathologies of dominant origin, its clinical course can be developed from a single defective gene Of one of the parents or from the development of a new mutation (National Organization for Rare Disorders, 2007).
Specifically, the proteins that generate the WNT5 and DVL1 genes appear to be involved in the same functional pattern as the ROR2, so the Presence of abnormalities and mutations in these, alters signaling pathways fundamental to physical development (Genetics Home Reference, 2016).
Diagnosis
The diagnosis of Robinow syndrome is fundamentally clinical, therefore, it is based on observation of the clinical course, the study of history Individual and family medical examination and physical examination.
Some findings should be confirmed through radiologic tests, especially bone abnormalities (limbs, skull, spine Vertebral, etc.) (Leon Herbert and La Urbina, 2013).
In addition to diagnosis during the infant or neonatal stage, it is also possible to confirm it during gestation. It is especially indicated, the study Of the length of different bone components, in fetal ultrasonography in cases of genetic risk (Leon Hervert and Loa Urbina, 2013).
On the other hand, in both cases, a genetic study is usually carried out to analyze the possible presence of genetic mutations that explain the origin of the Robinow syndrome (National Organization for Rare Disorders, 2007).
In addition, it is essential to make the differential diagnosis with other types of pathologies that have similar clinical features, especially the Presence of atypical facial features. In this way, the main pathologies that are discarded are the Hypertelorism , he syndrome of Aarskog-Scott or Opitz syndrome (Orphanet, 2011).
Treatment
There is currently no cure for Robinow's syndrome, so the therapeutic management of this disease focuses on the resolution of complications Medical conditions.
Musculoskeletal disorders are usually addressed through physical therapy, prosthesis placement or correction through procedures Surgical procedures (Orphanet, 2011).
On the other hand, cardiac and genital alterations are usually addressed through pharmacological and / or surgical treatments (National Organization for Rare Disorders, 2007).
In addition, there are also other types of novel therapies that are based on the administration of growth hormones, to stimulate the height. However, it can have several side effects, such as worsening of scoliosis (Leon Hervert and Loa Urbina, 2013).
In summary, early therapeutic intervention is essential for the correction of musculoskeletal disorders and the control of complications Such as cardiac manifestations.
Likewise, the work of multidisciplinary teams, physical, social and psychological intervention, is fundamental to promote the development of capacities and Skills in affected children (Leon Herbert and La Urbina, 2013).
In this way, the objective of the intervention is to allow the affected person to reach their maximum development potential, acquiring dependence Functional and an optimal quality of life (Leon Hervert and Loa Urbina, 2013).
References
- Díaz López, M., & Lorenzo Sanz, G. (1996). Robinow syndrome: Presentation of a family with autosomal dominant transmission. An Esp Pediatr, 250-523. Retrieved from"An Esp Pediatr.
- Leon Hervert, T., & Loa Urbina, M. (2013). Stomatological care of the pediatric patient with Robinow's syndrome. Arch. Invst Maternal Infant, 84-88.
- NIH. (2016). Robinow syndrome. Retrieved from the Genetics Home Reference.
- NORD. (2007). Robinow Syndrome. Retrieved from the National Organization for Rare Disorders.
- Orphanet. (2011). Robinow's syndrome. Obtained from Orphanet.