Download Coffin Siris Syndrome

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Coffin Siris Syndrome
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Copyright 1986, 1990, 1994, 1999, 2000, 2002
Synonyms of Coffin Siris Syndrome
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Dwarfism-Onychodysplasia
Fifth Digit Syndrome
Mental Retardation with Hypoplastic 5th Fingernails and Toenails
Short Stature-Onychodysplasia
Disorder Subdivisions
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No subdivisions found.
General Discussion
Coffin-Siris syndrome is a rare genetic disorder that may be evident at birth
(congenital). The disorder may be characterized by feeding difficulties and frequent
respiratory infections during infancy, diminished muscle tone (hypotonia), abnormal
looseness (laxity) of the joints, delayed bone age, and mental retardation. In addition,
affected infants and children typically have short fifth fingers ("pinkies") and toes
with underdeveloped (hypoplastic) or absent nails; other malformations of the fingers
and toes; and characteristic abnormalities of the head and facial (craniofacial) area,
resulting in a coarse facial appearance. Craniofacial malformations may include an
abnormally small head (microcephaly); a wide nose with a low nasal bridge; a wide
mouth with thick, prominent lips; thick eyebrows and eyelashes (hypertrichosis); and
sparse scalp hair.
The underlying cause of Coffin-Siris syndrome is unknown. In most cases, the
disorder is thought to result from new genetic changes (mutations) that appear to
occur randomly for unknown reasons (sporadically). Familial cases have also been
reported that suggest autosomal dominant or autosomal recessive inheritance.
Symptoms
Early in life, infants with Coffin-Siris syndrome typically experience feeding
difficulties, vomiting, slow growth, and frequent respiratory infections. In addition,
affected infants and children may have low muscle tone (hypotonia), abnormally loose
joints, delayed bone age, and mild to severe mental retardation.
Coffin-Siris syndrome is also characterized by distinctive abnormalities of the head
and facial (craniofacial) region. Affected individuals may have an unusually small
head (microcephaly); a wide mouth with full, prominent lips; a broad nasal tip; a low
nasal bridge; and an abnormally long vertical groove between the nose and the upper
lip (philtrum). Additional features may include thick eyebrows, long eyelashes, and
generalized excessive hair growth (hypertrichosis) with the exception of the scalp
hair, which tends to be relatively sparse (scalp hypotrichosis). Reports suggest that
sparse scalp hair improves with age.
Individuals with Coffin-Siris syndrome also have characteristic skeletal abnormalities.
For example, certain fingers and toes (digits), particularly the fifth fingers ("pinkies")
and toes, may be unusually short due to absence or underdevelopment (hypoplasia) of
the end bones (terminal phalanges) within these digits. The fingernails and toenails
may also be underdeveloped or absent. Additional abnormalities may include
dislocation of the inner forearm bone (radius) at the elbow, deformity of the hip (coxa
valga), or unusually small or absent knee caps (patellae).
Less commonly, affected individuals may have additional physical abnormalities,
such as choanal atresia, a malformation in which a bony or thin layer of tissue blocks
the passageway between the nose and throat, leading to difficulties breathing. Some
individuals with Coffin-Siris syndrome may also have heart abnormalities at birth
(congenital heart defects), such as persistence of the fetal channel that joins the main
artery of the body (aorta) and the pulmonary artery (patent ductus arteriosus) or an
abnormal opening in the fibrous partition (septum) that divides the upper or lower
chambers of the heart (atrial or ventricular septal defects). In addition, a brain
abnormality known as Dandy-Walker malformation has been reported in some cases.
This condition is characterized by cystic malformation and expansion of one of the
cavities in the brain (fourth ventricle). Dandy-Walker malformation is usually
associated with an abnormal accumulation of cerebrospinal fluid (CSF) in the skull
(hydrocephalus), resulting in increased fluid pressure, a rapid increase in head size,
abnormal prominence of the back region of the head (occiput), and/or other associated
findings. Some individuals with Coffin-Siris syndrome may also have partial or
complete absence of the band of nerve fibers that joins the two hemispheres of the
brain (agenesis of the corpus callosum).
Causes
The specific underlying cause of Coffin-Siris syndrome is not known. In most
affected individuals, the disorder is thought to result from new genetic changes
(mutations) that appear to occur randomly for unknown reasons (sporadically). In
addition, some familial cases have been reported. Some researchers suggest that such
cases may represent autosomal dominant inheritance with variable expression.
Human traits, including the classic genetic diseases, are the product of the interaction
of two genes, one received from the father and one from the mother. In autosomal
dominant disorders, a single copy of the disease gene (received from either the mother
or father) will be expressed "dominating" the other normal gene and resulting in the
appearance of the disease. The risk of transmitting the disorder from affected parent to
offspring is 50 percent for each pregnancy regardless of the sex of the resulting child.
In some dominant disorders, potentially including Coffin-Siris syndrome, disease
expression may be variable. In other words, if individuals inherit a mutated gene for
the disease, the characteristics that are manifested may vary greatly in range and
severity from case to case.
Other researchers indicate that Coffin-Siris syndrome may be inherited as an
autosomal recessive trait. In recessive disorders, the condition does not appear unless
a person inherits the same defective gene for the same trait from each parent. If an
individual receives one normal gene and one gene for the disease, the person will be a
carrier for the disease but usually will not show symptoms. The risk of transmitting
the disease to the children of a couple, both of whom are carriers for a recessive
disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease
but generally will not show symptoms of the disorder. Twenty-five percent of their
children may receive both normal genes, one from each parent, and will be genetically
normal (for that particular trait). The risk is the same for each pregnancy.
Parents of some individuals with Coffin-Siris syndrome have been closely related by
blood (consanguineous). In recessive disorders, if both parents carry the same gene for
the same disease trait, there is an increased risk that their children may inherit the two
genes necessary for development of the disease.
Some researchers also suggest that isolated (sporadic) and familial cases of CoffinSiris syndrome may be due to unknown chromosomal abnormalities. Further research
is required to determine the disorder's underlying cause and potential mode of
transmission.
Affected Populations
Coffin-Siris syndrome appears to affect females about four times more frequently than
males. Since the disorder was originally described in 1970 (G.S. Coffin),
approximately 40 cases have been reported.
Related Disorders
Symptoms of the following disorders may be similar to those of Coffin-Siris
syndrome. Comparisons may be useful for a differential diagnosis:
Chromosome 9 trisomy is a chromosomal disorder in which chromosome 9 appears
three times (trisomy) rather than twice in cells of the body. In most affected
individuals, only a percentage of cells may contain the chromosomal abnormality
(mosaicism). Associated symptoms may vary greatly, depending on the percentage of
cells affected or other factors. Affected infants typically have craniofacial
abnormalities, such as an unusually small head (microcephaly); small eyelid folds
(palpebral fissures); low-set, malformed ears; a small jaw; and a broad nose with a
wide tip. Chromosome 9 trisomy may also be characterized by underdevelopment of
bones within the fingers (phalanges); fixation or dislocation of certain joints; brain
malformations, such as absence of the band of nerve fibers that joins the two cerebral
hemispheres (agenesis of the corpus callosum); or congenital heart (cardiac) defects.
Such cardiac malformations may include an abnormal opening in the fibrous partition
(septum) that divides the upper or lower chambers of the heart (atrial or ventricular
septal defects) or abnormal persistence of the fetal channel that joins the main artery
of the body (aorta) and the pulmonary artery (patent ductus arteriosus). Chromosome
9 trisomy is thought to result from errors during the division of reproductive cells in
one of the parents (e.g., nondisjunction during meiosis) and/or errors during cellular
division after fertilization (mitosis). (For further information, choose "chromosome 9,
trisomy mosaic" as your search term in the Rare Disease Database.)
Other chromosomal disorders may have features similar to those associated with
Coffin-Siris syndrome. Chromosomal testing is necessary to confirm the specific
chromosomal abnormality present. (For further information on such disorders, choose
the name of the specific chromosomal disorder in question or use "chromosome" as
your search term in the Rare Disease Database.)
Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is apparent at birth
(congenital). Associated symptoms and findings typically include delays in physical
development before and after birth (prenatal and postnatal growth retardation);
characteristic craniofacial abnormalities, resulting in a distinctive facial appearance;
malformations of the hands and arms (upper limbs); and mild to severe mental
retardation. Many infants and children with the disorder have an unusually small,
short head (microbrachycephaly); an abnormally long vertical groove between the
upper lip and nose (philtrum); a depressed nasal bridge; upturned nostrils (anteverted
nares); and a protruding upper jaw (maxillary prognathism). Additional, characteristic
facial abnormalities may include thin, downturned lips; low-set ears; arched, welldefined eyebrows that grow together across the base of the nose (synophrys); an
unusually low hairline on the forehead and the back of the neck; and abnormally
curly, long eyelashes. Affected individuals may also have distinctive malformations of
the limbs, such as unusually small hands and feet, inward deviation (clinodactyly) of
the fifth fingers, or webbing (syndactyly) of certain toes. Less commonly, there may
be absence of the forearms, hands, and fingers. Infants with Cornelia de Lange
syndrome may also have feeding and breathing difficulties; an increased susceptibility
to respiratory infections; a low-pitched "growling" cry; heart defects; delayed skeletal
maturation; hearing loss; or other physical abnormalities. The range and severity of
associated symptoms and findings may be extremely variable from case to case. In
most individuals with the disorder, Cornelia de Lange syndrome appears to occur
randomly for unknown reasons (sporadically). However, there have been some
familial cases, suggesting autosomal dominant inheritance. (For further information,
choose "Cornelia de Lange" as your search term in the Rare Disease Database.)
There are additional congenital disorders that may be characterized by craniofacial
abnormalities, malformations of the hands and feet, and/or other symptoms and
findings similar to those potentially associated with Coffin-Siris syndrome. (For more
information on these disorders, choose the exact disease name in question as your
search term in the Rare Disease Database.)
Standard Therapies
Diagnosis
It is possible that a diagnosis of Coffin-Siris syndrome may be suggested before birth
(prenatally) based upon specialized tests such as ultrasound. During fetal
ultrasonography, reflected sound waves are used to generate an image of the
developing fetus. Ultrasound studies may reveal characteristic findings that may be
associated with the disorder.
The diagnosis of Coffin-Siris syndrome may be made at birth or during early infancy
(postnatally) based upon a thorough clinical evaluation and characteristic physical
findings. Specialized testing, such as certain advanced imaging techniques, may also
be conducted to detect certain findings that may be associated with the disorder.
Treatment
The treatment of Coffin-Siris syndrome is directed toward the specific symptoms that
are apparent in each individual. Such treatment may require the coordinated efforts of
a team of medical professionals who may need to systematically and comprehensively
plan an affected child's treatment. These professionals may include pediatricians;
physicians who specialize in disorders of the skeleton, joints, muscles, and related
tissues (orthopedists); physicians who diagnose and treat heart abnormalities
(cardiologists); physicians who specialize in digestive abnormalities; physical
therapists; and/or other health care professionals.
In some affected individuals, treatment may include surgical repair of certain
craniofacial, skeletal, cardiac, or other abnormalities potentially associated with the
disorder. The surgical procedures performed will depend upon the severity of the
anatomical abnormalities, their associated symptoms, and other factors.
In addition, in those with choanal atresia, surgery or other appropriate methods may
be required to decrease the airway obstruction or correct the malformation. If affected
individuals have Dandy-Walker malformation, treatment may include surgical
implantation of a specialized device (shunt) to drain excess cerebrospinal fluid (CSF)
away from the brain and into another part of the body where the CSF can be absorbed.
During infancy, treatment may also require measures to help prevent or aggressively
treat respiratory infections.
Early intervention may be important in ensuring that affected children reach their
potential. Special services that may be beneficial include special education, physical
therapy, or other medical, social, and/or vocational services. Genetic counseling will
also be of benefit for individuals with Coffin-Siris syndrome and their families. Other
treatment is symptomatic and supportive.
Investigational Therapies
Research on birth defects and their causes is ongoing. The National Institutes of
Health (NIH) is sponsoring the Human Genome Project which is aimed at mapping
every gene in the human body and learning why they sometimes malfunction. It is
hoped that this new knowledge will lead to prevention and treatment of genetic
disorder and chromosomal abnormalities in the future.
Information on current clinical trials is posted on the Internet at
www.clinicaltrials.gov. All studies receiving U.S. government funding, and some
supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in
Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
Organizations related to Coffin Siris Syndrome
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Genetic and Rare Diseases (GARD) Information Center
PO Box 8126
Gaithersburg, MD 20898-8126
Phone #: 301-251-4925
800 #: 888-205-2311
e-mail: N/A
Home page: http://rarediseases.info.nih.gov/GARD/
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National Foundation for Ectodermal Dysplasias
6 Execuitive Drive
Suite 2
Fairview Hiights, IL 62208
Phone #: 618-566-2020
800 #: -e-mail: [email protected]
Home page: http://www.nfed.org
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NIH/National Institute of Child Health and Human Development
31 Center Dr
Building 31, Room 2A32
MSC2425
Bethesda, MD 20892
Phone #: N/A
800 #: 800-370-2943
e-mail: [email protected]
Home page: http://www.nichd.nih.gov/
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The Arc
1825 K Street NW, Suite 1200
Washington, DC 20006
Phone #: 202-534-3700
800 #: 800-433-5255
e-mail: [email protected]
Home page: http://www.thearc.org
References
TEXTBOOKS
Jones KL. Smith's Recognizable Patterns of Human Malformation. 5th ed.
Philadelphia, PA: W.B. Saunders Company; 1997:582-583.
Adams RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill
Company; 1997:1003
Behrman RE, et al., eds. Nelson Textbook of Pediatrics. 15th ed. Philadelphia, PA:
W.B. Saunders Company; 1996:1684.
Gorlin RJ, et al., eds. Syndromes of the Head and Neck. 3rd ed. New York, NY:
Oxford University Press; 1990:831-832.
Buyse ML. Birth Defects Encyclopedia. Dover, MA: Blackwell Scientific
Publications, Inc.; 1990:355, 423-424.
ARTICLES
Braun-Quentin C, et al. Variant of Coffin-Siris syndrome or previously undescribed
syndrome? Am J Med Genet. 1996;64:568-572.
Swillen A, et al. The Coffin-Siris syndrome: data on mental development, language,
behavior and social skills in children. Clin Genet. 1995;48:177-182.
Bonioli E, et al. Autosomal recessive mode of inheritance of a Coffin-Siris like
syndrome. Genet Counsel. 1995;6:309-312.
deJong G, et al. Choanal atresia in two unrelated patients with the Coffin-Siris
syndrome. Clin Genet. 1992;42:320-322.
Levy P, et al. Coffin-Siris syndrome. J Med Genet. 1991;28:338-341.
Richieri-Costa A, et al. Coffin-Siris syndrome in a Brazilian child with
consanguineous parents. Rev Brasil Genet. 1986;IX:169-177.
Franceschini P, et al. The Coffin-Siris syndrome in two siblings. Pediat Radiol.
1986;16:330-333.
Haspeslagh M, et al. The Coffin-Siris syndrome: report of a family and further
delineation. Clin Genet. 1984;26:374-378.
Coffin GS, et al. Mental retardation with absent fifth fingernail and terminal phalanx.
Am J Dis Child. 1970;119:433-439.
FROM THE INTERNET
Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University,
Baltimore, MD. MIM Number 135900; 1/25/98. Available at:
http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?135900.