| Greig cephalopolysyndactyly syndrome | |
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| Patient with Greig cephalopolysyndactyly syndrome showing hypertelorism and macrocephaly. |
Greig cephalopolysyndactyly syndrome is a disorder that affects development of the limbs, head, and face. The features of this syndrome are highly variable, ranging from very mild to severe. People with this condition typically have one or more extra fingers or toes (polydactyly) or an abnormally wide thumb or big toe (hallux). [1]
The skin between the fingers and toes may be fused (cutaneous syndactyly). This disorder is also characterized by widely spaced eyes (ocular hypertelorism), an abnormally large head size (macrocephaly), and a high, prominent forehead. Rarely, affected individuals may have more serious medical problems including seizures and developmental delay. [1]
Greig cephalopolysyndactyly syndrome is a chromosomal condition related to chromosome 7. Mutations in the GLI3 gene cause Greig cephalopolysyndactyly syndrome. The GLI3 gene provides instructions for making a protein that controls gene expression, which is a process that regulates whether genes are turned on or off in particular cells. By interacting with certain genes at specific times during development, the GLI3 protein plays a role in the normal shaping (patterning) of many organs and tissues before birth. [1]
Different genetic changes involving the Gli3 gene can cause Greig cephalopolysyndactyly syndrome. In some cases, the condition results from a chromosomal abnormality, such as a large deletion or translocation of genetic material, in the region of chromosome 7 that contains the GLI3 gene. In other cases, a mutation in the GLI3 gene itself is responsible for the disorder. Each of these genetic changes prevents one copy of the gene in each cell from producing any functional protein. It remains unclear how a reduced amount of this protein disrupts early development and causes the characteristic features of Greig cephalopolysyndactyly syndrome. [1]
This condition is inherited in an autosomal dominant pattern, which means the defective gene is located on an autosome, and only one copy of the defective GLI3 gene is sufficient to cause the disorder. In cases of dominant inheritance, an affected person inherits the genetic mutation or chromosomal abnormality from one affected parent. [1]
Rare instances of this disorder are sporadic, and occur in people with no history of the condition in their family. [1]
The disease is not easily definable. The main form of diagnosis is presumptive, if the person has the usual triad of preaxial polydactyly with cutaneous syndactyly of at least one limb, macrocephaly, and hypertelorism. However, a definitive diagnosis can be made if there is a phenotype that is caused by a Gcps and a Gli3 gene mutation. It can also be made if the person has a family member or relative with the disease. Possibly, antenatal ultrasound can detect macrocephaly, and a high-resolution ultrasound can detect polydactyly and syndactyly. There are a lot of differential diagnoses, including over 100 syndromes and disorders that can cause polydactyly. However, there are a few diseases with an overlap that is significant. These diseases include: acrocallosal syndrome, carpenter syndrome, and Gorlin syndrome. [1]
The main treatment is surgery to fix the abnormalities in the limbs, like syndactyly. It is less important to repair the feet surgically, as it can cause complications, and it is not aesthetically important compared to the hands. If there is polydactyly with an extra digit that is fully functional, then the digit can stay. Some people may have intellectual disability, though this condition usually causes only mild impairment. Developmental assistance and early specialist intervention should be offered in the case of intellectual disability. People should be tested as an individual and be given proper assistance. [1]
The outlook is usually good in the usual case of GCPS. Mostly, the biggest problem associated with the condition in mild intellectual impairment.[ citation needed ]
The condition is named for David Middleton Greig FRSE. [2]
Macrocephaly is a condition in which circumference of the human head is abnormally large. It may be pathological or harmless, and can be a familial genetic characteristic. People diagnosed with macrocephaly will receive further medical tests to determine whether the syndrome is accompanied by particular disorders. Those with benign or familial macrocephaly are considered to have megalencephaly.
Saethre–Chotzen syndrome (SCS), also known as acrocephalosyndactyly type III, is a rare congenital disorder associated with craniosynostosis. This affects the shape of the head and face, resulting in a cone-shaped head and an asymmetrical face. Individuals with SCS also have droopy eyelids (ptosis), widely spaced eyes (hypertelorism), and minor abnormalities of the hands and feet (syndactyly). Individuals with more severe cases of SCS may have mild to moderate intellectual or learning disabilities. Depending on the level of severity, some individuals with SCS may require some form of medical or surgical intervention. Most individuals with SCS live fairly normal lives, regardless of whether medical treatment is needed or not.
Carpenter syndrome, also called acrocephalopolysyndactyly type II, is an extremely rare autosomal recessive congenital disorder characterized by craniofacial malformations, obesity, syndactyly, and polydactyly. Acrocephalopolysyndactyly is a variation of acrocephalosyndactyly that presents with polydactyly.
Zinc finger protein GLI3 is a protein that in humans is encoded by the GLI3 gene.
Simpson–Golabi–Behmel syndrome (SGBS) is a rare inherited congenital disorder that can cause craniofacial, skeletal, vascular, cardiac, and renal abnormalities. There is a high prevalence of cancer associated in those with SGBS which includes wilms tumors, neuroblastoma, tumors of the adrenal gland, liver, lungs and abdominal organs. The syndrome is inherited in an X-linked recessive manner. Females that possess one copy of the mutation are considered to be carriers of the syndrome but may still express varying degrees of the phenotype, suffering mild to severe malady. Males experience a higher likelihood of fetal death.
Nevoid basal-cell carcinoma syndrome (NBCCS) is an inherited medical condition involving defects within multiple body systems such as the skin, nervous system, eyes, endocrine system, and bones. People with this syndrome are particularly prone to developing a common and usually non-life-threatening form of non-melanoma skin cancer. About 10% of people with the condition do not develop basal-cell carcinomas (BCCs).
Pallister–Hall syndrome (PHS) is a rare genetic disorder that affects various body systems. The main features are a non-cancerous mass on the hypothalamus and extra digits (polydactylism). The prevalence of Pallister-Hall Syndrome is unknown; about 100 cases have been reported in publication.
Larsen syndrome (LS) is a congenital disorder discovered in 1950 by Larsen and associates when they observed dislocation of the large joints and face anomalies in six of their patients. Patients with Larsen syndrome normally present with a variety of symptoms, including congenital anterior dislocation of the knees, dislocation of the hips and elbows, flattened facial appearance, prominent foreheads, and depressed nasal bridges. Larsen syndrome can also cause a variety of cardiovascular and orthopedic abnormalities. This rare disorder is caused by a genetic defect in the gene encoding filamin B, a cytoplasmic protein that is important in regulating the structure and activity of the cytoskeleton. The gene that influences the emergence of Larsen syndrome is found in chromosome region, 3p21.1-14.1, a region containing human type VII collagen gene. Larsen syndrome has recently been described as a mesenchyme disorder that affects the connective tissue of an individual. Autosomal dominant and recessive forms of the disorder have been reported, although most cases are autosomal dominant. Reports have found that in Western societies, Larsen syndrome can be found in one in every 100,000 births, but this is most likely an underestimate because the disorder is frequently unrecognized or misdiagnosed.
Amastia refers to a rare clinical anomaly in which both internal breast tissue and the visible nipple are absent on one or both sides. It affects both men and women. Amastia can be either isolated or comorbid with other syndromes, such as ectodermal dysplasia, Syndactyly and lipoatrophic diabetes. This abnormality can be classified into various types, and each could result from different pathologies. Amastia differs from amazia and athelia. Amazia is the absence of one or both mammary glands but the nipples remain present, and athelia is the absence of one or both nipples, but the mammary gland remains.
Aarskog–Scott syndrome (AAS) is a rare disease inherited as X-linked and characterized by short stature, facial abnormalities, skeletal and genital anomalies. This condition mainly affects males, although females may have mild features of the syndrome.
3C syndrome is a rare condition whose symptoms include heart defects, cerebellar hypoplasia, and cranial dysmorphism. It was first described in the medical literature in 1987 by Ritscher and Schinzel, for whom the disorder is sometimes named.
Acrocallosal syndrome is an extremely rare autosomal recessive syndrome characterized by corpus callosum agenesis, polydactyly, multiple dysmorphic features, motor and intellectual disabilities, and other symptoms. The syndrome was first described by Albert Schinzel in 1979. Mutations in KIF7 are causative for ACLS, and mutations in GLI3 are associated with a similar syndrome.
Frontonasal dysplasia (FND) is a congenital malformation of the midface. For the diagnosis of FND, a patient should present at least two of the following characteristics: hypertelorism, a wide nasal root, vertical midline cleft of the nose and/or upper lip, cleft of the wings of the nose, malformed nasal tip, encephalocele or V-shaped hair pattern on the forehead. The cause of FND remains unknown. FND seems to be sporadic (random) and multiple environmental factors are suggested as possible causes for the syndrome. However, in some families multiple cases of FND were reported, which suggests a genetic cause of FND.
Hydrolethalus syndrome (HLS) is a rare genetic disorder that causes improper fetal development, resulting in birth defects and, most commonly, stillbirth.
Roberts syndrome, or sometimes called pseudothalidomide syndrome, is an extremely rare autosomal recessive genetic disorder that is characterized by mild to severe prenatal retardation or disruption of cell division, leading to malformation of the bones in the skull, face, arms, and legs.
Macrocephaly-capillary malformation (M-CM) is a multiple malformation syndrome causing abnormal body and head overgrowth and cutaneous, vascular, neurologic, and limb abnormalities. Though not every patient has all features, commonly found signs include macrocephaly, congenital macrosomia, extensive cutaneous capillary malformation, body asymmetry, polydactyly or syndactyly of the hands and feet, lax joints, doughy skin, variable developmental delay and other neurologic problems such as seizures and low muscle tone.
Ectrodactyly, split hand, or cleft hand involves the deficiency or absence of one or more central digits of the hand or foot and is also known as split hand/split foot malformation (SHFM). The hands and feet of people with ectrodactyly (ectrodactyls) are often described as "claw-like" and may include only the thumb and one finger with similar abnormalities of the feet.
Polysyndactyly is a congenital anomaly, combining polydactyly and syndactyly, in which affected individuals have an extra finger or toe that is connected, via fusing or webbing, to an adjacent digit.
Filippi syndrome, also known as Syndactyly Type I with Microcephaly and Mental Retardation, is a very rare autosomal recessive genetic disease. Only a very limited number of cases have been reported to date. Filippi Syndrome is associated with diverse symptoms of varying severity across affected individuals, for example malformation of digits, craniofacial abnormalities, intellectual disability, and growth retardation. The diagnosis of Filippi Syndrome can be done through clinical observation, radiography, and genetic testing. Filippi Syndrome cannot be cured directly as of 2022, hence the main focus of treatments is on tackling the symptoms observed on affected individuals. It was first reported in 1985.
Familial opposable triphalangeal thumb duplication is a limb malformation syndrome and a type of pre-axial polydactyly, characterized by having duplicated opposable triphalangeal thumbs. This condition can be a symptom of other genetic disorders, such as Holt–Oram syndrome and Fanconi anemia. This trait is autosomal dominant and often runs in families. Sometimes big toe duplication, post-axial polydactyly, and syndactyly of the hand and feet can occur alongside this malformation Approximately 20 families with the condition have been described in medical literature.