Baller-Gerold syndrome belongs to the group of malformation syndromes with predominant involvement of the face. The syndrome is due to mutations and is passed on in an autosomal dominant inheritance. Therapy is limited to symptomatic treatment, which consists largely of surgical correction of the malformations.
What is Baller-Gerold syndrome?
In the disease group of congenital malformation syndromes, malformation syndromes with predominant involvement of the face form their own subgroup. Baller-Gerold syndrome falls into this subgroup. The disease owes its name to the first descriptors F. Baller and M. Gerold, who first documented the clinical picture in the middle of the 20th century. The prevalence of the syndrome is reported to be one in 1000000. The leading symptoms of the symptom complex are the early closure of the cranial sutures in the sense of a craniosynostosis and the non-attachment of the radial bones. Current evidence suggests that Baller-Gerold syndrome is a hereditary condition resulting from genetic mutation.
Causes
Although Baller-Gerold syndrome is extremely rare, the cause is now known. A genetic mutation in the RECQL4 gene on chromosome 8q24.3 is responsible for the syndrome. The gene codes in human DNA for an enzyme called RecQ helicase. This enzyme unravels DNA strands and prepares them for reduplication. When the coding gene is mutated, the enzyme is defective and can no longer perform its task satisfactorily. The result is the individual symptoms of Baller-Gerold syndrome. In connection with the causative mutation, familial clustering has been observed, which speaks for the heritability of the disease. Apparently, the mutation is passed on in autosomal dominant inheritance. Whether, in addition to genetic factors, external factors such as exposure to toxins play a role in the development of the disease has not yet been fully elucidated.
Symptoms, complaints, and signs
Clinically, the symptom complex of Baller-Gerold syndrome is characterized by premature suture synostosis, which occurs before birth. Patients also suffer from a radially located radial defect associated with aplasia of the radius, sometimes including a malformation of the thumb. The thumb-sided carpus and metacarpal may also appear dysplastic or hypoplastic. The same is true for the finger extensor muscles located there. In addition, patients often suffer from short stature, which may be associated with skeletal malformations of the spine or malformations of the shoulder and pelvic girdle. Some of the affected individuals also suffer from a heart defect, are affected by anal atresia or have displaced kidneys. Facial dysmorphia often occurs in addition, which may manifest as hypertelorism, epicanthus, or prominent nasal bridge. Malformed auricles are also conceivable dysmorphias. Often, affected individuals are mentally retarded because of early suture closure. As infants, they sometimes suffer from poikiloderma. In children, the disease often manifests as hypoplasia of the patella. Because of the mutation, patients are also more prone to osteosarcoma formation.
Diagnosis and progression
In diagnosing Baller-Gerold syndrome, the physician must differentiate the clinical picture from clinically similar syndromes such as rapadilino syndrome or Rothmund-Thomson syndrome after the initial visual diagnosis. The same genetic mutation underlies these syndromes. The clinically relatively similar Saethre-Chotzen syndrome has a different cause, which must also be delineated. In addition, the radial defects of the syndrome must be differentiated from Roberts syndrome. If poikiloderma is present, this symptom is referred to as pathognomonic. Theoretically, there is a possibility of molecular genetic analysis for diagnosis and confirmation of diagnosis. The prognosis depends on the manifestations in the individual case. In the long-term course, for example, osteosarcomas that occur worsen the prognosis considerably.
Complications
Baller-Gerold syndrome can result in various complications, mainly leading to malpositions in the body. Usually, Baller-Gerold syndrome causes malformations of the skeleton and spine. These malformations are accompanied by short stature and have a very negative effect on the quality of life.Children in particular can suffer severely from short stature if they are teased or bullied because of the symptom. It is not uncommon for Baller-Gerold syndrome to be accompanied by mental retardation, causing the patient’s concentration and ability to learn to drop sharply. Often the affected person is dependent on the help and care of others. Due to the symptoms, there is a reduced life expectancy. There is also an increased likelihood of tumor formation, which can result in life-threatening complications that, in the worst case, can lead to death. Causal treatment of Baller-Gerold syndrome is usually performed immediately after birth through surgical intervention. Furthermore, the patient must take care to use plenty of sunscreen to avoid skin cancer. Baller-Gerold syndrome can cause gait problems and further fractures, which can make life difficult. However, symptoms can be limited with the use of walking aids.
When should you see a doctor?
A visit to the doctor should be made as soon as Baller-Gerold syndrome and similar syndromes are suspected. The physician can distinguish the disease from similar diseases after the first visual diagnosis and start treatment of the symptoms. Typical warning signs that require medical clarification are malformations of the carpus on the thumb side and of the metacarpal bone, especially of the thumb and the finger extensors. In addition, there are usually also malformations of the spine and the shoulder or pelvic girdle as well as short stature. Heart defects and malformed nasal roots, auricles and cheekbones may also occur. If any of these symptoms are noticed, a doctor must be consulted. However, the condition is usually diagnosed in childhood. Affected children are usually mentally retarded and are tested for Baller-Gerold syndrome during the initial examination after birth. If the syndrome is mild, the diagnosis is usually made in the first years of life. If the aforementioned clinical picture occurs, the affected child should be taken to the pediatrician in any case. This is especially true if slight deformities or mental problems have already been noticed in the past.
Treatment and therapy
Causal therapy is not available for patients with Baller-Gerold syndrome. Gene therapy approaches are currently at the forefront of medical research. However, they have not yet entered the clinical phase. For this reason, all diseases based on genetic mutations are incurable so far. Until gene therapy approaches are approved, such diseases are treated purely symptomatically. In malformation syndromes such as Baller-Gerold syndrome, symptomatic treatment usually corresponds to surgical resolution of the multiple malformations. Patients’ craniosynostosis is usually surgically corrected within the first six months to minimize subsequent symptoms. The thumb may be treated with reconstructive surgery. In most cases, this treatment is based on surgical transposition of the index fingers. Existing heart defects must be brought to correction as soon as possible. Surgical correction of displaced kidneys may also be necessary in individual cases. Mental retardation can be treated supportively by early intervention. As a rule, children supported in this way develop normal intelligence despite the syndrome. Because of their predisposition to cancer, patients with Baller-Gerold syndrome must also undergo regular preventive examinations as closely as possible. Often, affected individuals are advised to avoid sun exposure. This reduces susceptibility to cancers such as skin cancer. If cancer does break out, the disease is usually detected early enough by means of the close-meshed preventive examinations. In a large number of cases, those affected lead relatively normal lives in adulthood and enjoy little reduced quality of life.
Prevention
Preventive measures for genetic and mutational disorders such as Baller-Gerold syndrome exist only in moderation. After evidence of pathogenic RECQL4 mutations is obtained, affected parents may resort to prenatal diagnostics for further pregnancies and may decide not to have the child. Genetic counseling during family planning can also largely be described as a preventive measure.
You can do it yourself
Patients with Baller-Gerold syndrome suffer from malformations of some internal organs that require surgical correction. Self-help measures are not possible for these conditions, but the affected person supports the success of medical therapies by his behavior. Thus, during his stays in the clinic he follows the instructions of the doctors and supports the regeneration of the organism by sufficient rest. Often, the hand and fingers are affected by deformities that make everyday activities difficult. The patient improves his motor skills in the corresponding areas by undergoing physiotherapy and performing the learned training sessions at home. Similar therapy is also considered for any gait disorders, and the patient often uses additional walking aids. Sports activities are possible depending on the physical condition of the affected person and usually have a beneficial effect on well-being. However, it is a prerequisite that all sports activities are approved by a physician. If the disease is accompanied by impairments in cognitive performance, patients still receive a valuable education in special education schools. The social contacts that result from school attendance also enhance the quality of life of those affected. If the parents of the affected children develop depression or burnout as a result of the extra stress, they consult a psychological therapist as soon as possible.
