Primrose syndrome
Encyclopedia
Primrose syndrome is a rare, slowly progressive genetic disorder
that can vary symptomatically between individual cases, but is generally characterised by ossification
of the external ears, learning difficulties
, and facial abnormalities. It was first described in 1982 in Scotland
's Royal National Larbert Institution by Dr D.A.A. Primrose.
Primrose syndrome appears to occur spontaneously, regardless of family history. The cause is currently unknown and there are no known treatments.
pinnae, learning disabilities or mental retardation, hearing problems, movement disorders (ataxia
, paralysis, and parkinsonism
among others (likely due, in part, to calcification of the basal ganglia
), a torus palatinus
(a neoplasm on the mouth's hard palate), muscle atrophy, and distorted facial features. Other symptoms usually occur, different in each case, but it is unknown whether or not these symptoms are caused by the same disease.
In the case studied by Dalai et al. in 2010, it was found that an abnormally high amount of calcitonin
, a hormone secreted by the thyroid gland
to stabilize blood calcium levels, was present in the blood serum. This suggests that the thyroid gland is releasing an abnormal amount of calcitonin, resulting in the disruption of calcium level homeostasis. No molecular cause was found, but an expanded microarray analysis
of the patient found a 225.5 kb deletion on chromosome 11p
between rs12275693 and rs1442927. Whether or not this deletion is related to the syndrome or is a harmless mutation is unknown. The deletion was not present in the patient's mother's DNA sample, but the father's DNA was unavailable.
s had ossified. Additional symptoms included muscle atrophy in the legs and hands, deafness, cataracts, and a tissue mass covering the roof of his mouth.
In 1986, Calacott et al. described a mentally handicapped patient whose pinnae had ossified. The patient also experienced deafness, cataracts, skeletal deformities, and muscle atrophy. As the second reported case of such symptoms, it suggested that these symptoms were part of one entity, named "Primrose syndrome"
In 1996, Lindor et al. reported a 43-year-old male patient with schizophrenia, as well as other neurological disorders, and severe pinnae calcification. Additional symptoms included hearing loss, stiffened joints, and facial deformities.
In 2006, Mathijssen et al. described an adult male mentally retarded patient who had calcified pinnae and a neoplasm of the palate. The patient also had extensive hearing loss, little to no body hair, distorted facial features, and joint contractures
. The patient also developed testicular cancer, but it is unknown whether or not it is related to the syndrome. The patient experienced cryptorchidism
, a birth defect where one of the testes is not present at birth, that may have played a part in the formation of the tumor.
In 2010, another similar case was studied extensively by Dalal et al. The patient was a mentally retarded 43-year-old woman who had hearing impairment, distorted facial features, muscle atrophy, cataracts, and ossification of cartilage. Additionally, she was born with Ebstein malformation
, a congenital heart defect
, agenesis of the corpus callosum
, and hip dysplasia
. Other symptoms included hypothyroidism
, diabetes
, and muscle control problems. A brain MRI
showed that her basal ganglia
had partially calcified, which may have contributed to her paraparesis and motor tics.
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
that can vary symptomatically between individual cases, but is generally characterised by ossification
Ossification
Ossification is the process of laying down new bone material by cells called osteoblasts. It is synonymous with bone tissue formation...
of the external ears, learning difficulties
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
, and facial abnormalities. It was first described in 1982 in Scotland
Scotland
Scotland is a country that is part of the United Kingdom. Occupying the northern third of the island of Great Britain, it shares a border with England to the south and is bounded by the North Sea to the east, the Atlantic Ocean to the north and west, and the North Channel and Irish Sea to the...
's Royal National Larbert Institution by Dr D.A.A. Primrose.
Primrose syndrome appears to occur spontaneously, regardless of family history. The cause is currently unknown and there are no known treatments.
Symptoms
The common symptoms in all reported cases of primrose syndrome include ossifiedOssification
Ossification is the process of laying down new bone material by cells called osteoblasts. It is synonymous with bone tissue formation...
pinnae, learning disabilities or mental retardation, hearing problems, movement disorders (ataxia
Ataxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
, paralysis, and parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
among others (likely due, in part, to calcification of the basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
), a torus palatinus
Torus palatinus
Torus palatinus [palatinus torus in English] is a bony protrusion on the palate. Palatal tori are usually present on the midline of the hard palate...
(a neoplasm on the mouth's hard palate), muscle atrophy, and distorted facial features. Other symptoms usually occur, different in each case, but it is unknown whether or not these symptoms are caused by the same disease.
Pathophysiology
The cause of Primrose syndrome is currently unknown. The syndrome is extremely rare and seems to spontaneously occur, regardless of family history.In the case studied by Dalai et al. in 2010, it was found that an abnormally high amount of calcitonin
Calcitonin
Calcitonin is a 32-amino acid linear polypeptide hormone that is producedin humans primarily by the parafollicular cells of the thyroid, and in many other animals in the ultimobranchial body. It acts to reduce blood calcium , opposing the effects of parathyroid hormone . Calcitonin has been found...
, a hormone secreted by the thyroid gland
Thyroid
The thyroid gland or simply, the thyroid , in vertebrate anatomy, is one of the largest endocrine glands. The thyroid gland is found in the neck, below the thyroid cartilage...
to stabilize blood calcium levels, was present in the blood serum. This suggests that the thyroid gland is releasing an abnormal amount of calcitonin, resulting in the disruption of calcium level homeostasis. No molecular cause was found, but an expanded microarray analysis
DNA microarray
A DNA microarray is a collection of microscopic DNA spots attached to a solid surface. Scientists use DNA microarrays to measure the expression levels of large numbers of genes simultaneously or to genotype multiple regions of a genome...
of the patient found a 225.5 kb deletion on chromosome 11p
Chromosome 11 (human)
thumb|right|Chromosome 11 ChartChromosome 11 is one of the 23 pairs of chromosomes in humans. Humans normally have two copies of this chromosome. Chromosome 11 spans about 134.5 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells...
between rs12275693 and rs1442927. Whether or not this deletion is related to the syndrome or is a harmless mutation is unknown. The deletion was not present in the patient's mother's DNA sample, but the father's DNA was unavailable.
Cases
There have been very few reported cases of Primrose syndrome worldwide. The first known case was described by D.A. Primrose in 1982. The patient was a 33-year-old mentally retarded male whose outer earOuter ear
The outer ear is the external portion of the ear, which consists of the pinna, concha, and external auditory meatus. It gathers sound energy and focuses it on the eardrum . One consequence of the configuration of the external ear is to selectively boost the sound pressure 30- to 100-fold for...
s had ossified. Additional symptoms included muscle atrophy in the legs and hands, deafness, cataracts, and a tissue mass covering the roof of his mouth.
In 1986, Calacott et al. described a mentally handicapped patient whose pinnae had ossified. The patient also experienced deafness, cataracts, skeletal deformities, and muscle atrophy. As the second reported case of such symptoms, it suggested that these symptoms were part of one entity, named "Primrose syndrome"
In 1996, Lindor et al. reported a 43-year-old male patient with schizophrenia, as well as other neurological disorders, and severe pinnae calcification. Additional symptoms included hearing loss, stiffened joints, and facial deformities.
In 2006, Mathijssen et al. described an adult male mentally retarded patient who had calcified pinnae and a neoplasm of the palate. The patient also had extensive hearing loss, little to no body hair, distorted facial features, and joint contractures
Contracture
A muscle contracture is a permanent shortening of a muscle or joint.. It is usually in response to prolonged hypertonic spasticity in a concentrated muscle area, such as is seen in the tightest muscles of people with conditions like spastic cerebral palsy....
. The patient also developed testicular cancer, but it is unknown whether or not it is related to the syndrome. The patient experienced cryptorchidism
Cryptorchidism
Cryptorchidism is the absence of one or both testes from the scrotum. It is the most common birth defect regarding male genitalia. In unique cases, cryptorchidism can develop later in life, often as late as young adulthood. About 3% of full-term and 30% of premature infant boys are born with at...
, a birth defect where one of the testes is not present at birth, that may have played a part in the formation of the tumor.
In 2010, another similar case was studied extensively by Dalal et al. The patient was a mentally retarded 43-year-old woman who had hearing impairment, distorted facial features, muscle atrophy, cataracts, and ossification of cartilage. Additionally, she was born with Ebstein malformation
Ebstein's anomaly
Ebstein anomaly is a congenital heart defect in which the opening of the tricuspid valve is displaced towards the apex of the right ventricle of the heart.-Presentation:...
, a congenital heart defect
Congenital heart defect
A congenital heart defect is a defect in the structure of the heart and great vessels which is present at birth. Many types of heart defects exist, most of which either obstruct blood flow in the heart or vessels near it, or cause blood to flow through the heart in an abnormal pattern. Other...
, agenesis of the corpus callosum
Agenesis of the corpus callosum
Agenesis of the corpus callosum is a rare birth defect in which there is a complete or partial absence of the corpus callosum. Agenesis of the corpus callosum occurs when the corpus callosum, the band of white matter connecting the two hemispheres in the brain, fails to develop normally,...
, and hip dysplasia
Hip dysplasia (human)
Hip dysplasia, developmental dysplasia of the hip or congenital dysplasia of the hip is a congenital or acquired deformation or misalignment of the hip joint.-Terminology:...
. Other symptoms included hypothyroidism
Hypothyroidism
Hypothyroidism is a condition in which the thyroid gland does not make enough thyroid hormone.Iodine deficiency is the most common cause of hypothyroidism worldwide but it can be caused by other causes such as several conditions of the thyroid gland or, less commonly, the pituitary gland or...
, diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, and muscle control problems. A brain MRI
Magnetic resonance imaging of the brain
Magnetic resonance imaging of the brain and brain stem uses magnetic fields and radio waves to produce high quality two- or three-dimensional images of brain structures without use of ionizing radiation or radioactive tracers....
showed that her basal ganglia
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
had partially calcified, which may have contributed to her paraparesis and motor tics.
External links
- Primrose syndrome at Online Mendelian Inheritance in Man
- Primrose syndrome at The National Library of MedicineUnited States National Library of MedicineThe United States National Library of Medicine , operated by the United States federal government, is the world's largest medical library. Located in Bethesda, Maryland, the NLM is a division of the National Institutes of Health...
archives - Journal of Neurology article