Coffin Siris Syndrome

Coffin Siris Syndrome

National Organization for Rare Disorders, Inc.

Important

It is possible that the main title of the report Coffin Siris Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.

Synonyms

  • Dwarfism-Onychodysplasia
  • Fifth Digit Syndrome
  • Mental Retardation with Hypoplastic 5th Fingernails and Toenails
  • Short Stature-Onychodysplasia

Disorder Subdivisions

  • None

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 Coffin-Siris 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.

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: prpl@cc.nih.gov



For information about clinical trials sponsored by private sources, contact:

www.centerwatch.com

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.

Resources

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For a Complete Report

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