CDAGS syndrome is the medical term for a rare complex of malformations associated primarily with cranial anomalies. The symptom complex has a hereditary basis and results from mutation on chromosome 22. No causal therapy exists to date.
What is CDAGS syndrome?
CDAGS syndrome is also known as CAP syndrome and corresponds to an extremely rare inherited disorder. The prevalence is estimated to be one case per 1,000,000 people. The disease was first described in the 21st century. R. Mendoza-Londono and his associates are considered the first descriptor and eponym. The name CDAGS syndrome is an acronym. This acronym contains the clinical feature combination that distinguishes the symptom complex. In this context, the C stands for craniosynostosis, the D abbreviates “delayed” and refers to delayed closure of the fontanelle or “deafness”. A codes for the anal malformations associated with the syndrome. The G gets the acronym because of the genital malformations with which the condition is symptomatically associated, and the S stands for “skin” and indicates the dermal changes within the clinical picture. The syndrome falls into the group of unspecified malformation syndromes and corresponds to a congenital disorder.
Causes
CDAGS syndrome has a genetic basis. The syndrome does not appear to occur sporadically but to be subject to autosomal recessive inheritance. So far, the complex of symptoms has only been described within four families. In all of them a familial clustering was present, which confirms the assumption of a genetic component. Thus, the symptoms were found in seven individuals within the four families. A hereditary mutation is the cause of the symptom complex. Despite the few cases documented so far, the genetic cause has now been linked to specific genes. Thus, the mutation affects the genes of chromosome 22 on the gene locus 22q12-q13. Chromosome 22 is the second smallest chromosome in humans and contains between 500 and 800 genes, of which 508 are known to date. Mutations of the genes on chromosome 22 are involved in many different diseases. Examples include trisomy 22, Epstein syndrome and Sebastian syndrome. Which genes of the chromosome may play a role in the development of CDAGS syndrome is the subject of research. At present, we can only speculate about the primary causative factors of the syndrome. In addition to toxin exposure during pregnancy, numerous other factors may be considered as activating factors for the genetic disposition.
Symptoms, complaints, and signs
Cranial anomalies characterize the clinical picture of CDAGS syndrome. These are malformations that affect the skull. Most characteristic of the syndrome is synostosis of the cranial suture. The term synostosis refers to a bony fusion of several bones that were formerly cartilaginous or connected by connective tissue. Synostosis of the cranial suture is associated with widely open fontanelles in the anterior and posterior regions in patients with CDAGS syndrome. The patients’ parietal foramina are also strikingly large. The parietal foramen is part of the os parietale and corresponds to an opening on the superior parietal bone through which the parietal vein passes. In addition to these anomalies of the skull, affected individuals usually suffer from keratinization and thus cornification disorders inform porokeratosis, which appears as dermal exanthema. Affected individuals are also frequently affected by sensorineural hearing loss up to absolute deafness. Anal and urogenital abnormalities complete the picture. These symptoms are associated with a severe delay in mental and motor development. In some circumstances, there is additional underdevelopment of the clavicles.
Diagnosis
Usually, the diagnosis of CDAGS syndrome is made in infancy. The first suspicion reaches the physician already by visual diagnosis. To confirm the suspicion, imaging of the skull may be ordered to provide evidence of the cranial abnormalities. Dermatological tests may also be performed as part of the diagnostic process. To confirm the diagnosis beyond doubt, the physician may order molecular genetic tests. A mutation on chromosome 22 confirms the suspicion of the syndrome.
Complications
Due to CDAGS syndrome, the patient is affected by various malformations and deformities. In this case, these have a negative effect mainly on the skull and can lead to discomfort of the bones. The head is conspicuously large, which leads to reduced aesthetics. In many cases, this leads to teasing and bullying, especially in children. This can lead to psychological complaints. It is not uncommon for CDAGS syndrome to also result in decreased hearing or even complete deafness. This can also place a heavy burden on the life and daily routine of the affected person. However, there is no reduction in intelligence, so that the affected person can usually understand and comprehend thought processes. A causal treatment of the CDAGS syndrome is not possible. Only the symptoms can be limited, but there are no further complications. The limitation of the symptoms is done by surgical interventions or with the help of various therapies. However, it cannot be predicted whether these will lead to a positive course of the disease. In most cases, life expectancy is not reduced by CDAGS syndrome.
When should you see a doctor?
CDAGS syndrome is usually diagnosed in infancy. A visit to the doctor is necessary if the malformations cause complications. For example, if the child suffers from bone pain or decreased hearing, the appropriate specialist must be contacted. The same applies to all minor and major complications associated with the CDAGS syndrome These must be treated in any case to allow the child to live a symptom-free life despite the disease. In the case of severe malformations, surgery may also be possible. Such an operation must take place at an early stage, because otherwise permanent developmental disorders may develop. If there is a suspicion of psychological suffering, triggered for example by teasing and bullying, the child should seek therapeutic counseling together with the parents. In general, children and adults with CDAGS syndrome must be closely monitored by an experienced specialist. Since hereditary disorders can trigger nonspecific symptoms, various medical professionals should be consulted who can give the affected person a good picture of the symptoms and possible therapeutic procedures.
Treatment and therapy
To date, no causal treatments are available to patients with CDAGS syndrome. For one thing, the chromosome but not the responsible gene has been identified. For another, although gene therapy has been a research topic, it is not yet applicable. Patients with the syndrome are treated symptomatically for this reason. This symptomatic treatment includes, for example, corrections of the cranial anomalies, which are usually performed surgically. However, surgical solution of the synostosis is only carried out if there are problems that are clearly due to the adhesion. The surgery gives the brain more room to grow. If the surgery is done early enough, it can mitigate the patient’s developmental problems. Patients’ anal and urogenital abnormalities can also usually be improved with surgery. These steps are usually less urgent than skull correction, however, because restricted brain growth is associated with far more secondary problems. The porokeratosis of affected individuals can be treated by conventional medications, such as the administration of keratolytics, which dissolve the horny layer. To compensate for mental and motor developmental delays, early intervention and physical therapy may be useful.
Outlook and prognosis
CDAGS syndrome cannot be treated by causal therapy. For this reason, only symptomatic treatment options are available to the affected person, but these cannot completely limit the disease. The various malformations and deformities can be corrected with the help of surgical interventions. If no treatment occurs, these malformations and adhesions remain and lead to severe limitations in the life of the affected person. Early diagnosis and treatment of CDAGS syndrome can reduce and minimize disruptions in the development of the affected individual.If the skull correction does not take place, the brain usually cannot grow without further treatment, so that mental disorders and, in the worst case, brain death may occur. With timely treatment, these complaints can be prevented. The further complaints are usually alleviated with the help of medication. Since the CDAGS syndrome also leads to reduced intelligence and motor and mental complaints, these are compensated for by special support. However, this also does not provide a complete cure. However, with early therapy, CDAGS syndrome does not negatively affect the patient’s life expectancy.
Prevention
To date, CDAGS syndrome cannot be prevented. For example, the primary causative factors are currently not known in detail, so the scope for action is limited.
Here’s what you can do yourself
Before taking self-help measures, those affected by CDGAS syndrome should first talk to the doctor in charge. In most cases, the individual symptoms and conditions can only be treated surgically, and self-help measures such as applying ointments to the abscesses often cause secondary symptoms. Therefore, it is important to clarify the next steps with a specialist. First and foremost, the doctor will recommend a healthy lifestyle and regular exercise. Accompanying physiotherapeutic measures are indicated. Physiotherapy, yoga and the like help to stabilize the immune system and prevent late effects such as hemorrhoids on the anus or abscesses on the skullcap. Depending on the severity of the CDGA syndrome, it may also be necessary to promote mental abilities. This should always be done under professional supervision. However, the relatives and friends of the affected person can support the respective therapy – in which way depends on the individual complaints and the constitution of the affected person. Psychological support is also important. Since those affected usually suffer greatly from the abnormalities, emotional support is all the more important, especially in the case of mental limitations or a poor general prognosis.
