Greig syndrome is a medical term for a congenital malformation syndrome associated primarily with facial deformities and multi-jointedness of the fingers and toes. Although the hereditary syndrome cannot be cured, it can be treated surgically. Patients with the mutation-related disease are considered to have an excellent prognosis.
What is Greig syndrome?
Greig syndrome is also called Greig cephalopolysyndactyly syndrome and is a congenital malformation syndrome associated with congenital anomalies, facial deformities, and finger anomalies. Related syndromes include acrocallosal syndrome and Pallister-Hall syndrome. Synonyms for the symptom complex are cephalopolysyndactyly or Hoodnick-Holmes syndrome. In the early 20th century, the syndrome was first described and documented as a separate symptom complex. The author of the first description was the Scottish physician David Middleton Greig, who gave the syndrome its name. In 1972, U.S. orthopedic surgeon David Randall Hootnick and pediatrician Levis B. Holmes on Greig syndrome, which made the synonym Hoodnick-Holmes syndrome common to describe the condition. Meanwhile, despite the rarity of the disorder, the causative gene has already been isolated.
Causes
The cause of Greig syndrome is a genetic abnormality that is thought to be a gene mutation. This mutation affects the GLI3 gene, which is located on the short arm of chromosome 7 (7p13). In acrocallosal syndrome and Pallister-Hall syndrome, mutations of the same gene are present. Since the genetic cause of the syndrome is already considered established, heritability can be assumed. The causative gene codes for a transcription factor and loses its function when mutated. Thus, Greig syndrome is an allelic disease that is passed on in an autosomal dominant inheritance. One gene each consists of a homologous pair of chromosomes. In autosomal dominant inherited disorders, one defective allele is sufficient for trait expression. Thus, 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 per 1,000,000.
Symptoms, complaints, and signs
The leading symptoms of Greig syndrome are hypertelorism, macrocephaly, a balcony forehead, and polysyndactyly. Thus, the skull of affected individuals 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-limb. In addition, membranous syndactyls occur as accompanying symptoms. Adjacent fingers or toes are cutaneously fused as part of this manifestation. In individual cases, the central nervous system of affected individuals also shows malformations. Hernias and cognitive impairment are conceivable, but occur extremely rarely as symptoms. As a rule, the cognitive and physical development of the patients is not further affected by the malformations. Organic anomalies or functional impairments are not typical symptoms of the disease. Because the symptomatology of Greig syndrome is considered relatively nonspecific, diagnosis is difficult.
Diagnosis and course
Because of the nonspecific symptoms and the previous lack of sensitive diagnostic criteria, the diagnosis of Greig syndrome can prove difficult both prenatally and after the child is born. For a tentative diagnosis, evidence of the triad of preaxial polydactyly with membranous syndactyly, hypertelorism, and macrocephaly is sufficient. If this trais is incomplete, the patient’s phenotype can be verified. 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, provided their phenotype matches the characteristics of Greig syndrome. The prognosis is considered excellent. Only rarely does physically and mentally delayed development occur. Deletion of major regions of the mutated gene may slightly worsen the prognosis.
Complications
Greig syndrome causes the patient to develop various malformations and deformities. These occur mainly on the face and hands and feet.Patients have an increased number of phalanges and toes, which can lead to bullying or teasing, especially in children. The facial complaints can also have a negative effect on aesthetics, leading to inferiority complexes or lowered self-esteem. As a rule, however, Greig’s syndrome does not result in any health limitations. 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 limited 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 foregone completely if Greig syndrome does not cause limitations in the patient’s daily life. There are usually no special complications during the surgical interventions. To prevent subsequent damage in adulthood, these procedures are usually performed a few months after birth.
When should you go to the doctor?
Because Greig syndrome is not always associated with severe symptoms, it is not necessary to see a doctor until there are limitations in the patient’s daily life due to the symptoms. However, regular examinations are always advisable when the syndrome is diagnosed to avoid further complications in the child’s life. A visit to the doctor should be made if the skull is larger than average and if the patient suffers from multi-fingers. Malformations of the organs or nervous system can also occur due to Greig syndrome and should always be examined by a doctor. Especially with the limitation of cognitive and motor skills, the patient is often dependent on special support in school and in his daily life. Since many affected persons also suffer from psychological complaints or depression due to Greig’s syndrome, psychological treatment is also very useful. Often the parents or relatives of the affected person are also dependent on this treatment. As a rule, Greig’s syndrome is diagnosed in the hospital after birth or by a general practitioner. However, further treatment depends on the exact manifestation of the symptoms and is carried out by the respective specialist.
Treatment and therapy
Causal therapy is not available for Greig syndrome. Symptomatic treatment is equivalent to surgical intervention. Most anomalies of Greig syndrome can be corrected via corrective surgery. Polydactyly and syndactyly, in particular, can be surgically corrected. In the case of radially located extra finger or foot phalanges, the supernumerary radial phalanx is removed. Modifications, such as narrowing of the bone or correction of ligaments, may be required. Corrective osteotomy is performed for axial desviations in the hands or feet. If the interfinger spaces are too narrow, Z-plasty, pivoting or rotational flaps may be considered as corrective measures. In extremely complex polydactyls, fusion of the bones may be required. In addition to plastic surgery, the multiple malformations of Greig syndrome can be treated with orthopedic surgery or intervention. If the malformations are not significant and the patient is neither physically limited nor psychologically distressed by the abnormalities, further treatment of the condition is often not required. If the decision is made to operate because of significant malformation, the correction usually does not take place before the sixth month of life. Especially in polydactyls and syndactyls, the smaller the patient’s fingers and toes, the more difficult it is to perform corrective surgery.
Outlook and prognosis
The prognosis of Greig syndrome is considered extremely favorable. Although the gene mutation is not curable for legal and scientific reasons, correction of the malformations can still be initiated with the available options. In a surgical procedure, the multiple limbs of toes and fingers are changed and adapted to the normal natural specifications. The limbs that were formed too much during the formation process in the womb are removed. This eliminates the visual defect and the syndrome is considered cured.Surgical treatment is associated with the usual risks and side effects. Nevertheless, these are comparatively minor. If the procedure is successful, scars remain on the affected areas, which can be treated cosmetically in the further course if desired. From a medical point of view, however, there is no disease value. In rare cases, Greig syndrome patients are additionally diagnosed with physical or mental retardation. Short stature may occur or difficulties in coping with everyday life may occur due to mental impairment. This worsens the otherwise favorable prognosis, as further disorders and irregularities are to be expected throughout life. Emotional and psychological problems may occur, leading to mental illness over the lifespan. In these patients, the prognosis depends on an assessment of the overall situation.
Prevention
Greig syndrome cannot be prevented to date because the cause of the mutation has not yet been determined. Environmental toxins and other harmful influences during pregnancy are possible causes. However, heritability argues against this thesis.
Follow-up
In Greig syndrome, the options for aftercare are usually very limited and only barely possible. Affected persons are therefore primarily dependent on direct and medical treatment by a physician for this disease, although self-healing cannot occur either. Since Greig’s syndrome is a hereditary disease, it cannot be completely treated. If there is a desire to have children, genetic counseling may be useful to prevent the syndrome from being passed on to descendants. The treatment of this disease is usually done by surgical interventions. The patient should always rest after such procedures and also take care of his body. Strenuous or sporting activities should be refrained from in order not to put unnecessary strain on the body. Likewise, stressful activities should always be avoided. Furthermore, psychological treatments are often necessary in the case of malformations. Support from one’s own family or friends has a very positive effect on the further course of the disease. Thereby, it cannot be universally predicted whether Greig syndrome will reduce the life expectancy of the affected person.
What you can do yourself
In Greig syndrome, treatment focuses on relieving individual symptoms. Parents of an affected child can support drug and surgical therapy with some measures and, in some circumstances, with various household and natural remedies. First, however, an orthopedist must be consulted. This is especially necessary in the case of severe deformities of the fingers or feet, as these often have to be removed and replaced. Depending on how severe a deformity is, crutches, a wheelchair and other aids may be used in the interim. In the long term, a prosthesis must be made. Complex polydactyls usually also cause severe pain. The doctor will prescribe various painkillers and sedatives in this case. Parents should primarily pay attention to unusual symptoms and report them to the doctor. This way, the particular medication can be adjusted optimally without causing side effects and other complications. Since visual changes are always present in Greig’s syndrome, therapeutic counseling for the child is also useful. At the latest, if psychological complaints occur, a psychologist should be consulted.
