Robinow syndrome
Encyclopedia
Robinow syndrome is an extremely rare genetic disorder
characterized by short-limbed dwarfism
, abnormalities in the head, face, and external genitalia
, as well as vertebral segmentation. The disorder was first described in 1969 by human geneticist
Meinhard Robinow, along with physician
s Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.
Two forms of the disorder exist, dominant and recessive, of which the former is more common. Patients with the dominant version often suffer moderately from the aforementioned symptoms. Recessive cases, on the other hand, are usually more physically marked, and individuals may exhibit more skeletal
abnormalities. The recessive form is particularly frequent in Turkey
. However, this can likely be explained by a common ancestor, as these patients' families can be traced to a single town in Eastern Turkey. Clusters of the autosomal
recessive form have also been documented in Oman
and Czechoslovakia
.
The syndrome is also known as Robinow-Silverman-Smith syndrome, Robinow dwarfism, fetal face, fetal face syndrome, fetal facies syndrome, acral dysostosis with facial and genital abnormalities, or mesomelic dwarfism-small genitalia syndrome. The recessive form was previously known as Covesdem syndrome.
, using the term "fetal facies" to describe the appearance of a small face and widely spaced eyes. Clinical features also may include a short, upturned nose, a prominent forehead, and a flat nasal bridge. The upper lip may be "tented," exposing dental crowding, "tongue tie
," or gum
hypertrophy.
Though the eyes do not protrude, abnormalities in the lower eyelid
may give that impression. Surgery may be necessary if the eyes cannot close fully. In addition, the ear
s may be set low on the head or have a deformed pinna.
Patients suffer from dwarfism, short lower arms, small feet, and small hands. Fingers and toes may also be abnormally short
and laterally or medially bent. The thumb may be displaced and some patients, notably in Turkey, experience ectrodactyly
. All patients often suffer from vertebral segmentation abnormalities. Those with the dominant variant have, at most, a single butterfly vertebra. Those with the recessive form, however, may suffer from hemivertebrae, vertebral fusion, and rib anomalies. Some cases resemble Jarcho-Levin syndrome
or spondylocostal dysostosis.
Genital defects characteristically seen in males include a micropenis
with a normally developed scrotum
and testes. Sometimes, testicles may be undescended, or the patient may suffer from hypospadias
. Female genital defects may include a reduced size clitoris
and underdeveloped labia minora
. Infrequently, the labia majora
may also be underdeveloped. Some research has shown that females may experience vaginal atresia
or haematocolpos.
The autosomal recessive form of the disorder tends to be much more severe. Examples of differences are summarized in the following table:
, developmental problems, respiratory problems, eating difficulties, light sensitivity
, and esophageal reflux.
Data on fertility
and the development of secondary sex characteristics is relatively sparse. It has been reported that both male and female patients have had children. Males who have reproduced have all suffered from the autosomal dominant form of the disorder; the fertility of those with the recessive variant is unknown.
Researchers have also reported abnormalities in the renal tract of affected patients. Hydronephrosis
is a relatively common condition, and researchers have theorized that this may lead to urinary tract infection
s. In addition, a number of patients have suffered from cystic dysplasia of the kidney
.
A number of other conditions are often associated with Robinow syndrome. About 15% of reported patients suffer from congenital heart defect
s. Though there is no clear pattern, the most common conditions include pulmonary stenosis and atresia
. In addition, though intelligence is generally normal, around 15% of patients show developmental problems.
studies have linked the autosomal recessive form of the disorder to the ROR2
gene
on position 9 of the long arm of chromosome 9
. The gene is responsible for aspects of bone and cartilage growth. This same gene is involved in causing autosomal dominant brachydactyly B.
The autosomal dominant form has not been linked to a specific gene, though those related to ROR2 are being studied. This form is often caused by new mutations. Alternatively, it may be passed from a parent who is so mildly affected by the disorder that he or she has not been diagnosed.
A fetal ultrasound
can offer prenatal diagnosis
19 weeks into pregnancy
. However, the characteristics of a fetus suffering from the milder dominant form may not always be easy to differentiate from a more serious recessive case. Genetic counseling
is an option given the availability of a family history.
Meinhard Robinow, along with physician
s Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.
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....
characterized by short-limbed dwarfism
Dwarfism
Dwarfism is short stature resulting from a medical condition. It is sometimes defined as an adult height of less than 4 feet 10 inches , although this definition is problematic because short stature in itself is not a disorder....
, abnormalities in the head, face, and external genitalia
Sex organ
A sex organ, or primary sexual characteristic, as narrowly defined, is any of the anatomical parts of the body which are involved in sexual reproduction and constitute the reproductive system in a complex organism; flowers are the reproductive organs of flowering plants, cones are the reproductive...
, as well as vertebral segmentation. The disorder was first described in 1969 by human geneticist
Geneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
Meinhard Robinow, along with physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.
Two forms of the disorder exist, dominant and recessive, of which the former is more common. Patients with the dominant version often suffer moderately from the aforementioned symptoms. Recessive cases, on the other hand, are usually more physically marked, and individuals may exhibit more skeletal
Skeleton
The skeleton is the body part that forms the supporting structure of an organism. There are two different skeletal types: the exoskeleton, which is the stable outer shell of an organism, and the endoskeleton, which forms the support structure inside the body.In a figurative sense, skeleton can...
abnormalities. The recessive form is particularly frequent in Turkey
Turkey
Turkey , known officially as the Republic of Turkey , is a Eurasian country located in Western Asia and in East Thrace in Southeastern Europe...
. However, this can likely be explained by a common ancestor, as these patients' families can be traced to a single town in Eastern Turkey. Clusters of the autosomal
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
recessive form have also been documented in Oman
Oman
Oman , officially called the Sultanate of Oman , is an Arab state in southwest Asia on the southeast coast of the Arabian Peninsula. It is bordered by the United Arab Emirates to the northwest, Saudi Arabia to the west, and Yemen to the southwest. The coast is formed by the Arabian Sea on the...
and Czechoslovakia
Czechoslovakia
Czechoslovakia or Czecho-Slovakia was a sovereign state in Central Europe which existed from October 1918, when it declared its independence from the Austro-Hungarian Empire, until 1992...
.
The syndrome is also known as Robinow-Silverman-Smith syndrome, Robinow dwarfism, fetal face, fetal face syndrome, fetal facies syndrome, acral dysostosis with facial and genital abnormalities, or mesomelic dwarfism-small genitalia syndrome. The recessive form was previously known as Covesdem syndrome.
Signs and symptoms
Robinow noted the resemblance of affected patients' faces to that of a fetusFetus
A fetus is a developing mammal or other viviparous vertebrate after the embryonic stage and before birth.In humans, the fetal stage of prenatal development starts at the beginning of the 11th week in gestational age, which is the 9th week after fertilization.-Etymology and spelling variations:The...
, using the term "fetal facies" to describe the appearance of a small face and widely spaced eyes. Clinical features also may include a short, upturned nose, a prominent forehead, and a flat nasal bridge. The upper lip may be "tented," exposing dental crowding, "tongue tie
Ankyloglossia
Ankyloglossia, commonly known as tongue tied, is a congenital oral anomaly which may decrease mobility of the tongue tip and is caused by an unusually short, thick lingual frenulum, a membrane connecting the underside of the tongue to the floor of the mouth...
," or gum
Gingiva
The gingiva , or gums, consists of the mucosal tissue that lies over the mandible and maxilla inside the mouth.-General description:...
hypertrophy.
Though the eyes do not protrude, abnormalities in the lower eyelid
Eyelid
An eyelid is a thin fold of skin that covers and protects an eye. With the exception of the prepuce and the labia minora, it has the thinnest skin of the whole body. The levator palpebrae superioris muscle retracts the eyelid to "open" the eye. This can be either voluntarily or involuntarily...
may give that impression. Surgery may be necessary if the eyes cannot close fully. In addition, the ear
Ear
The ear is the organ that detects sound. It not only receives sound, but also aids in balance and body position. The ear is part of the auditory system....
s may be set low on the head or have a deformed pinna.
Patients suffer from dwarfism, short lower arms, small feet, and small hands. Fingers and toes may also be abnormally short
Brachydactyly
Brachydactyly , is a medical term which literally means "shortness of the fingers and toes" . The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an inherited, usually dominant trait...
and laterally or medially bent. The thumb may be displaced and some patients, notably in Turkey, experience ectrodactyly
Ectrodactyly
Ectrodactyly, sometimes referred to as the “Lobster-Claw Syndrome” 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...
. All patients often suffer from vertebral segmentation abnormalities. Those with the dominant variant have, at most, a single butterfly vertebra. Those with the recessive form, however, may suffer from hemivertebrae, vertebral fusion, and rib anomalies. Some cases resemble Jarcho-Levin syndrome
Jarcho-Levin syndrome
Spondylocostal dysostosis is a rare, heritable axial skeleton growth disorder. It is characterized by widespread and sometimes severe malformations of the vertebral column and ribs, shortened thorax, and moderate to severe scoliosis and kyphosis...
or spondylocostal dysostosis.
Genital defects characteristically seen in males include a micropenis
Micropenis
Micropenis is an unusually small penis. A common criterion is a dorsal erect penile length of at least 2.5 standard deviations smaller than the mean human penis size. The condition is usually recognized shortly after birth...
with a normally developed scrotum
Scrotum
In some male mammals the scrotum is a dual-chambered protuberance of skin and muscle containing the testicles and divided by a septum. It is an extension of the perineum, and is located between the penis and anus. In humans and some other mammals, the base of the scrotum becomes covered with curly...
and testes. Sometimes, testicles may be undescended, or the patient may suffer from hypospadias
Hypospadias
Hypospadias is a birth defect of the urethra in the male that involves an abnormally placed urinary meatus...
. Female genital defects may include a reduced size clitoris
Clitoris
The clitoris is a sexual organ that is present only in female mammals. In humans, the visible button-like portion is located near the anterior junction of the labia minora, above the opening of the urethra and vagina. Unlike the penis, which is homologous to the clitoris, the clitoris does not...
and underdeveloped labia minora
Labia minora
The labia minora , also known as the inner labia, inner lips, or nymphae, are two flaps of skin on either side of the human vaginal opening, situated between the labia majora...
. Infrequently, the labia majora
Labia majora
The labia majora are two prominent longitudinal cutaneous folds that extend downward and backward from the mons pubis to the perineum and form the lateral boundaries of the pudendal cleft, which contains the labia minora, interlabial sulci, clitoral hood, clitoral glans, frenulum clitoridis, the...
may also be underdeveloped. Some research has shown that females may experience vaginal atresia
Vaginal atresia
Vaginal Atresia is a birth defect or congenital abnormality of the female genitourinary system that manifests itself in the absence of a vagina , or a deformed and nonfunctional vagina ....
or haematocolpos.
The autosomal recessive form of the disorder tends to be much more severe. Examples of differences are summarized in the following table:
| Characteristic | Autosomal dominant | Autosomal recessive |
|---|---|---|
| Stature | More than 2 SD Standard deviation Standard deviation is a widely used measure of variability or diversity used in statistics and probability theory. It shows how much variation or "dispersion" there is from the average... shorter |
Short or normal |
| Arms | Very short | Slightly short |
| Elbow | Radial head dislocation | No dislocation |
| Upper lip | very broad | Tented |
| Mortality rate | Normal | 10% |
Associated conditions
Medical conditions include frequent ear infection, hearing loss, hypotoniaHypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, developmental problems, respiratory problems, eating difficulties, light sensitivity
Photophobia
Photophobia is a symptom of abnormal intolerance to visual perception of light. As a medical symptom photophobia is not a morbid fear or phobia, but an experience of discomfort or pain to the eyes due to light exposure or by presence of actual physical photosensitivity of the eyes, though the term...
, and esophageal reflux.
Data on fertility
Fertility
Fertility is the natural capability of producing offsprings. As a measure, "fertility rate" is the number of children born per couple, person or population. Fertility differs from fecundity, which is defined as the potential for reproduction...
and the development of secondary sex characteristics is relatively sparse. It has been reported that both male and female patients have had children. Males who have reproduced have all suffered from the autosomal dominant form of the disorder; the fertility of those with the recessive variant is unknown.
Researchers have also reported abnormalities in the renal tract of affected patients. Hydronephrosis
Hydronephrosis
Hydronephrosis is distension and dilation of the renal pelvis calyces, usually caused by obstruction of the free flow of urine from the kidney, leading to progressive atrophy of the kidney...
is a relatively common condition, and researchers have theorized that this may lead to urinary tract infection
Urinary tract infection
A urinary tract infection is a bacterial infection that affects any part of the urinary tract. Symptoms include frequent feeling and/or need to urinate, pain during urination, and cloudy urine. The main causal agent is Escherichia coli...
s. In addition, a number of patients have suffered from cystic dysplasia of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
.
A number of other conditions are often associated with Robinow syndrome. About 15% of reported patients suffer from 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...
s. Though there is no clear pattern, the most common conditions include pulmonary stenosis and atresia
Atresia
Atresia is a condition in which a body orifice or passage in the body is abnormally closed or absent.Examples of atresia include:* Imperforate anus - malformation of the opening between the rectum and anus....
. In addition, though intelligence is generally normal, around 15% of patients show developmental problems.
Genetics
GeneticGenetics
Genetics , a discipline of biology, is the science of genes, heredity, and variation in living organisms....
studies have linked the autosomal recessive form of the disorder to the ROR2
ROR2
Tyrosine-protein kinase transmembrane receptor ROR2 also known as neurotrophic tyrosine kinase, receptor-related 2, is a protein that in humans is encoded by the ROR2 gene located on position 9 of the long arm of chromosome 9. This protein is responsible for aspects of bone and cartilage growth. It...
gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
on position 9 of the long arm of chromosome 9
Chromosome 9 (human)
125px|rightChromosome 9 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome, as they normally do with all chromosomes...
. The gene is responsible for aspects of bone and cartilage growth. This same gene is involved in causing autosomal dominant brachydactyly B.
The autosomal dominant form has not been linked to a specific gene, though those related to ROR2 are being studied. This form is often caused by new mutations. Alternatively, it may be passed from a parent who is so mildly affected by the disorder that he or she has not been diagnosed.
A fetal ultrasound
Ultrasound
Ultrasound is cyclic sound pressure with a frequency greater than the upper limit of human hearing. Ultrasound is thus not separated from "normal" sound based on differences in physical properties, only the fact that humans cannot hear it. Although this limit varies from person to person, it is...
can offer prenatal diagnosis
Prenatal diagnosis
Prenatal diagnosis or prenatal screening is testing for diseases or conditions in a fetus or embryo before it is born. The aim is to detect birth defects such as neural tube defects, Down syndrome, chromosome abnormalities, genetic diseases and other conditions, such as spina bifida, cleft palate,...
19 weeks into pregnancy
Pregnancy
Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...
. However, the characteristics of a fetus suffering from the milder dominant form may not always be easy to differentiate from a more serious recessive case. Genetic counseling
Genetic counseling
Genetic counseling or traveling is the process by which patients or relatives, at risk of an inherited disorder, are advised of the consequences and nature of the disorder, the probability of developing or transmitting it, and the options open to them in management and family planning...
is an option given the availability of a family history.
History
The disorder was first described in 1969 by human geneticistGeneticist
A geneticist is a biologist who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a researcher or lecturer. Some geneticists perform experiments and analyze data to interpret the inheritance of skills. A geneticist is also a Consultant or...
Meinhard Robinow, along with physician
Physician
A physician is a health care provider who practices the profession of medicine, which is concerned with promoting, maintaining or restoring human health through the study, diagnosis, and treatment of disease, injury and other physical and mental impairments...
s Frederic N. Silverman and Hugo D. Smith, in the American Journal of Diseases of Children. By 2002, over 100 cases had been documented and introduced into medical literature.