C syndrome is a rare MCA/MR syndrome and is consequently associated with congenital multiple malformations as well as decreased intelligence. The exact causes of the syndrome are not fully understood, as only 40 cases have been described to date. Treatment is exclusively symptomatic, with parents usually assisted by a psychologist.
What is C syndrome?
Syndromes are repeated combinations of clinically similar symptoms, usually due to the same cause. Medical science recognizes numerous types of these. One of them is called the MCA/MR syndrome. The common feature of all MCA/MR syndromes is symptoms such as multiple congenital anomalies and mental retardation. Jacobsen syndrome is among the best known syndromes from this group. Less well known is C syndrome, which is estimated to have a prevalence of one to nine in one million. The syndrome is also referred to in the medical literature as OTCS, Opitz C trigonocephaly, Opitz trigonocephaly C syndrome, and Opitz trigonocephaly syndrome, trigonocephaly C syndrome, or Opitz type trigonocephalus syndrome. In 1969, John Marius Opitz, along with collaborators Johnson, McCredie, and Smith, first described the syndrome. The case report had as its focus two siblings whose external features pointed to the presence of a syndrome. To date, C syndrome has not been conclusively studied. About 40 cases have been described so far. A major focus of current research is on specifying a phenotype.
Causes
C syndrome was documented in a sibling in the initial description, suggesting familial clustering. However, most cases appear to be sporadic. Inheritance is usually not applicable. Since the syndrome seems to be extremely variable in its phenotypic expression, different causes are assumed for the cases documented so far. Due to the lack of specification in the context of the characteristic phenotype, it remains unclear so far whether the cases described as C syndrome are actually patients with the same disease. Thus, different diseases may have been described as C-syndrome so far. In some of the documented patients a chromosomal aberration could be detected. This anomaly in the genetic material could be the cause of C syndrome. On the other hand, microdeletions were documented in still other cases. In addition, exogenous causation in the context of C syndrome suggests a connection with valproate syndrome. Germ cell mosaics are also discussed as a cause.
Symptoms, complaints, and signs
Patients with C syndrome may suffer from a clinically fundamentally different symptom picture. In addition to mongoloid eyelid axes, thick epicanthal folds, and capillary hemangioma at the midline of the forehead, documented facial anomalies include, for example, strabismus, a flat nasal bridge, a short or thick nasal septum, and wide columella, a flat philtrum, and narrow labial red. Microgenia, a high and narrow palate, buccal frenulas and gingival frenulas, and malformed ears or cleft palate have also been reported. Often the neck of the patients appears shortened, so especially due to the neck hygroma. Skeletal anomalies such as short rhizo- or acromelic limb segments, a hypermobile elbow including crepitations, polydactyly or syndactyly, and coccyx humps or deformed thoracic regions seem to be the rule. These malformation syndromes are usually associated with mental retardation. However, patients with average IQ have also been documented. Cerebral spasms have been reported in isolated cases. Hernias, genital anomalies, anal defects, and cardiovascular features may be present as well as renal dystrophy to renal agenesis.
Diagnosis and course
The diagnosis of C syndrome is made on the basis of the clinical picture. The initial tentative diagnosis can be reasonably confirmed by findings on cerebral MRI, echocardiogram, and ultrasonography. Differentially, syndromes such as Smith-Lemli-Opitz syndrome should be distinguished. Prenatal diagnosis of C syndrome is theoretically possible by malformation ultrasound. However, prenatal growth is largely normal. Only symptoms such as severe renal malformations and oligohydramnios of the pregnant woman suggest abnormalities.The prognosis for patients with C syndrome is relatively unfavorable. Mortality is estimated to be approximately 50 percent due to multiple organ malformations.
Complications
C syndrome causes various malformations or deformities in the patient. Usually, the patient’s intelligence is also negatively affected by C syndrome, resulting in mental retardation. Not infrequently, those are then dependent on the help of other people to be able to cope with everyday life. As a rule, the parents are also psychologically affected by the C-syndrome and suffer from severe depression and other psychological complaints, which is why treatment by a psychologist is necessary. The patient suffers from cleft palate due to the syndrome. Furthermore, there are anomalies of the skeleton and therefore a possible restriction of movement. The quality of life of the affected person is considerably limited by the syndrome. Furthermore, kidney problems and anomalies of the genitals occur. It is not uncommon for heart defects to develop, which can lead to cardiac death if left untreated. Treatment of C syndrome cannot be causal. Certain deformities and conditions can be treated with therapies and surgical procedures. However, life expectancy is greatly reduced by the syndrome. Without treatment, this results in premature death of the patient.
When should you see a doctor?
In most cases, C syndrome is diagnosed before birth or immediately after birth, so re-diagnosis is usually not necessary. However, the doctor should be seen to treat the deformities and symptoms. If the affected person suffers from eye discomfort or strabismus, the ophthalmologist should be consulted. If these symptoms are detected and corrected at an early stage, further complications of the eyes can be prevented. Medical treatment and consultation is also necessary for deformities of the body or face. Parents should also consult a doctor if the child suffers from mental discomfort or depression due to C syndrome. Special support is also necessary in case of reduced intelligence. If the patient suffers from cramps, these must also be examined. In particular, diseases of the kidneys often occur, so this region must be examined particularly closely. However, the treatment of further complaints depends strongly on their severity and usually consists of various surgical interventions and therapies.
Treatment and therapy
Causal therapy is not yet available for patients with C syndrome. Thus, the disease is currently incurable. Not only are the causes insufficiently understood to date to develop a causal therapy. Also, the causes probably lie in the genes, so that only the approval of gene therapy approaches could make a causal treatment possible at all. Patients are currently treated purely symptomatically and supportively. Treatment of the vital organs is the focus of therapy. Invasive procedures must be used to correct heart defects, kidney malformations, and malformations of the thoracic region to ensure the patient’s viability. Once the life-threatening symptoms are corrected, the other malformations can be treated by plastic surgery. Mental retardation can be addressed with early intervention if necessary. The parents of the patients also receive supportive measures. For example, they are helped to cope with their child’s illness. This support usually consists of the provision of a psychotherapist or psychologist. In addition, the relatives receive genetic counseling. Based on documented sibling cases, parents of a C syndrome patient are recommended malformation ultrasound for all subsequent pregnancies.
Prospect and prognosis
Treatment of C syndrome proves difficult in most cases because very few cases of this disorder have been reported. Due to the genetic defect, the symptoms can also only be treated symptomatically, with no causal treatment. A complete cure of the syndrome does not occur for this reason. Even with treatment, the reduced intelligence usually cannot be completely resolved, so that the affected person is dependent on intensive therapy.Furthermore, the patients are always dependent on help in their daily lives and usually cannot cope with everyday life on their own. The various malformations of the body and organs can be corrected by surgical intervention. In general, this does not lead to further complications. Whether C syndrome reduces the patient’s life expectancy depends largely on the success of the treatment and the severity of the malformations. Not in every case can the organs be corrected in such a way that life expectancy remains unchanged. Because C syndrome is a genetic disorder, parents should undergo genetic counseling to prevent recurrence of the syndrome.
Prevention
The causes of C syndrome have not yet been sufficiently elucidated to develop promising preventive measures. At this time, the only option for prevention is malformation ultrasound. Couples cannot be completely assured by this type of ultrasound that their unborn child does not have syndromes, but they can be assured to the greatest extent possible. If the ultrasound suggests a syndrome, they can decide against having the baby.
Follow-up
After the various malformations of the skull, bones, and joints have been surgically corrected, the patient must attend regular medical follow-up. Depending on the patient’s constitution, the time between medical checkups can range from a few months to a few years. If no further complications occur, the follow-up examinations can be gradually reduced. Due to the large number of possible complaints that can develop as a result of C syndrome in the course of life, regular medical clarification is necessary in any case. In this way, any heart defects, joint contractures or hemangiomas can be quickly detected and treated. C syndrome cannot be completely cured, as there are usually too many and too severe symptoms. Accordingly, patients are dependent on treatment for the rest of their lives. Follow-up care may also include medication to treat any pain and accompanying symptoms. For example, for severe wound healing pain, the physician may prescribe tramadol or diclofenac. After surgical treatment of a heart defect, the patient must see a specialist who may also need to readjust the pacemaker. C syndrome can cause symptoms of varying intensity. Therefore, follow-up care must be decided individually for each patient.
Here’s what you can do yourself
The condition of C syndrome does not allow the sufferer to perform self-help measures to a sufficient extent. Because of the symptoms present, the affected person must receive permanent care as well as medical attention. In everyday life, close relatives therefore need tips and advice on how to cope well with the situation. It is important for them to receive comprehensive information about the disease and its symptoms. They also need advice on how to ensure optimal care for the patient. The burden on the relatives should be taken into account. A good social environment is helpful for mutual support. To prevent psychological overload, self-help groups or exchanges with family members of other sufferers can be very helpful. As a balance to caregiving, regular participation in social life should take place. Stress-reducing techniques can be used to cope well with the challenges ahead in everyday life. Various relaxation techniques and a healthy lifestyle support the relative to have enough inner strength. Conversations or therapeutic support help in processing the situation and ensure psychological stability. Despite all adversities, courage to face life and a confident approach to the disease can be very beneficial for the patient as well as for the relatives.
