Medicine understands the Greig syndrome as a congenital malformation syndrome that is primarily associated with facial deformities and a multi-joint structure of the fingers and toes. Although the hereditary syndrome cannot be cured, it can be treated surgically. The prognosis for patients with the mutation-related disease is excellent.
What is Greig Syndrome?
Greig syndrome, also called Greig cephalopolysyndactyly syndrome, is a congenital malformation syndrome associated with congenital anomalies, facial deformities, and finger anomalies. Related clinical pictures are the acrocallosal syndrome and the Pallister-Hall syndrome. Synonyms for the symptom complex include cephalopolysyndactyly or Hoodnick -Holmes syndrome.
According to abbreviationfinder.org, the syndrome was first described at the beginning of the 20th century and documented as a separate symptom complex. The author of the first description was the Scottish doctor David Middleton Greig, who gave the syndrome its name. In 1972, the American orthopedist David Randall Hootnick and the pediatrician Levis B. Holmes published Greig syndrome, which made the synonym Hoodnick-Holmes syndrome used to describe the disease. Despite the rarity of the disease, the causative gene has now been isolated.
Causes
The cause of Greig syndrome is a genetic abnormality suspected to be a gene mutation. This mutation affects the GLI3 gene, which is on the short arm of chromosome 7 (7p13). Mutations in the same gene are present in acrocallosal syndrome and Pallister-Hall syndrome. Since the genetic cause of the syndrome has already been proven, it can be assumed that it is hereditary. The causative gene encodes a transcription factor and loses its function in the event of a mutation.
This makes Greig syndrome an allelic disease that is passed on in an autosomal dominant inheritance. A gene consists of a homologous pair of chromosomes. In the case of autosomal dominant hereditary diseases, one defective allele is sufficient for characteristic expression. The healthy allele cannot compensate for the defects of the defective allele in these diseases. The prevalence of Greig syndrome is estimated to be about 1 to 9 in 1,000,000.
Symptoms, Ailments & Signs
The cardinal symptoms of Greig syndrome are hypertelorism, macrocephaly, a balcony forehead, and polysyndactyly. The skull of those affected is larger than average compared to the rest of the body. There is an above-average distance between the eyes of the patients and the feet and hands are multi-jointed. In addition, cutaneous syndactyly occurs as an accompanying symptom.
Adjacent fingers or toes are cutaneously fused as part of this phenomenon. In individual cases, the central nervous system of those affected also shows malformations. Hernias and cognitive impairments are conceivable, but are extremely rare as symptoms.
As a rule, the cognitive and physical development of the patients is not further impaired by the malformations. Organic abnormalities or loss of function are not typical symptoms of the disease. Since the symptoms of Greig syndrome are considered to be relatively unspecific, diagnosis is difficult.
Diagnosis & History
Because of the non-specific symptoms and the lack of sensitive diagnostic criteria to date, the diagnosis of Greig syndrome can be difficult both prenatally and after the birth of the child. Evidence of the triad of preaxial polydactyly with cutaneous syndactyly, hypertelorism, and macrocephaly is sufficient for the presumptive diagnosis.
If this trais is incomplete, the patient’s phenotype can be checked. If the phenotype is compatible with the characteristics of Greig syndrome and a GLI3 mutation is present, the disease is considered definitively diagnosed even with incomplete Trais. Autosomal dominant relatives of the diagnosed patient can also be definitively diagnosed if their phenotype matches the characteristics of Greig syndrome.
The prognosis is considered excellent. Physically and mentally delayed development occurs only rarely. Deleting larger areas of the mutated gene can slightly worsen the prognosis.
Complications
The Greig syndrome leads to various malformations and deformities in the patient. These mainly appear on the face, hands and feet. The patients have an increased number of finger joints and toes, which can lead to bullying or teasing, especially in children. Facial complaints can also have a negative effect on aesthetics and lead to inferiority complexes or reduced self-esteem.
As a rule, however, there are no health restrictions due to Greig syndrome. The internal organs are also not affected by the syndrome, so that there are no further complaints or complications. Life expectancy is also not reduced or restricted by this syndrome. Greig syndrome cannot be treated causally. However, it is possible to limit and eliminate most malformations and deformities through surgical intervention.
In some cases, treatment is dispensed with entirely if the Greig syndrome does not impair the patient’s everyday life. As a rule, there are no special complications during the surgical interventions. In order to avoid consequential damage in adulthood, these interventions are usually carried out a few months after birth.
When should you go to the doctor?
Since Greig syndrome is not always associated with severe symptoms, the doctor only has to be consulted if the patient’s everyday life is restricted due to the symptoms. However, regular check-ups are always advisable when diagnosing the syndrome in order to avoid further complications in the child’s life.
A visit to the doctor should be made when the skull is larger than average and when the patient suffers from multi-fingeredness. Malformations of the organs or the nervous system can also occur as a result of Greig syndrome and should always be examined by a doctor.
Especially when cognitive and motor skills are restricted, the patient is often dependent on special support at school and in everyday life. Since many of those affected also suffer from psychological complaints or depression as a result of Greig syndrome, psychological treatment is also very useful.
Often the parents or relatives of those affected are also dependent on this treatment. As a rule, Greig syndrome is diagnosed in the hospital after birth or by a general practitioner. However, further treatment depends on the exact severity of the symptoms and is carried out by the respective specialist.
Treatment & Therapy
A causal therapy is not available for Greig syndrome. The symptomatic treatment corresponds to a surgical intervention. Most abnormalities in Greig syndrome can be corrected with corrective surgery. Polydactyly and syndactyly in particular can be corrected surgically. In the case of radially located, additional phalanxes of the fingers or feet, the surplus radial phalanx is removed.
Modifications, such as narrowing of the bone or correction of ligaments, may be necessary. A corrective osteotomy is performed for axis deviations on the hands or feet. If the interfinger spaces are too narrow, Z-plasty, pivoting or rotation flaps can be used as corrective measures. Bone fusion may be required in extremely complex polydactyly.
In addition to plastic surgery, the multiple malformations of Greig syndrome can be treated with orthopedic surgery or interventions. If the malformations are not significant and the patient is neither physically restricted nor psychologically burdened by the anomalies, no further treatment of the disease is often necessary.
If the decision to operate is made because of a significant malformation, the correction usually does not take place before the sixth month of life. Especially in the case of polydactyly and syndactyly, corrective surgery is more difficult the smaller the patient’s fingers and toes are.
Outlook & Forecast
The prognosis of Greig syndrome is considered extremely favorable. Although the gene mutation cannot be cured for legal and scientific reasons, the malformations can still be corrected with the available options.
In a surgical procedure, the multi-joint structure of the toes and fingers is changed and adapted to the normal, natural specifications. The limbs that have overgrown during the process of formation in the womb are removed. This eliminates the visual flaw and the syndrome is considered cured.
Surgical treatment comes with the usual risks and side effects. Nevertheless, these are comparatively small. If the procedure is successful, scars remain on the affected areas, which can be treated cosmetically later on if desired. From a medical point of view, however, there is no disease value.
In rare cases, patients with Greig syndrome are also diagnosed with physical or mental retardation. Short stature can occur or difficulties in coping with everyday life can arise due to the mental impairment.
This worsens the prognosis, which is otherwise so favorable, since further disturbances and irregularities are to be expected in the course of life. Emotional and psychological problems can arise that lead to mental illness over the lifespan. In these patients, the prognosis depends on the assessment of the overall situation.
Prevention
So far, Greig syndrome cannot be prevented because the cause of the mutation has not yet been established. Environmental toxins and other harmful influences during pregnancy are possible causes. However, heredity speaks against this thesis.
Aftercare
In the case of Greig syndrome, the options for aftercare are usually very limited and hardly possible. Those affected by this disease are therefore primarily dependent on direct and medical treatment by a doctor, although self-healing cannot occur. Since Greig syndrome is a hereditary disease, it cannot be fully treated.
If there is a desire to have children, genetic counseling can be useful to prevent the syndrome from being passed on to the descendants. This disease is usually treated by surgery. The patient should always rest after such procedures and also take care of his body.
Strenuous or sporting activities should be avoided in order not to unnecessarily strain the body. Likewise, stressful activities should always be avoided. Furthermore, psychological treatments are often necessary for the malformations. The support of one’s own family or friends has a very positive effect on the further course of the disease. It cannot be universally predicted whether Greig syndrome will reduce the life expectancy of those affected.
You can do that yourself
For Greig syndrome, treatment focuses on relieving individual symptoms. The parents of an affected child can support the medical and surgical therapy with a number of measures and possibly also with various household and natural resources.
First, however, an orthopedist must be consulted. This is necessary above all in the case of severe malformations on the fingers or feet, as these often have to be removed and replaced. Depending on how severe a malformation is, crutches, a wheelchair and other aids can be used in the meantime. In the long term, a prosthesis must be made.
In complex polydactyly, there is usually severe pain. The doctor will prescribe various painkillers and sedatives here. Parents should primarily look out for any unusual symptoms and report them to the doctor.
In this way, the respective drug can be optimally adjusted without side effects or other complications occurring. Since there are always visual changes in Greig syndrome, therapeutic advice for the child is also useful. A psychologist should be consulted at the latest when mental health problems arise.
