NORD gratefully acknowledges Shashikant Kulkarni, PhD, Director of CytoGenomics and Molecular Pathology, Director of Clinical & Molecular Cytogenetics, Department of Pathology, Washington University School of Medicine, for assistance in the preparation of this report.
Chromosome 14 Ring is a rare disorder that is characterized by abnormalities of the 14th chromosome. Affected infants and children typically have delays in the acquisition of skills that require the coordination of physical and mental activities (psychomotor delays), mental retardation, growth delays, and episodes of uncontrolled electrical activity in the brain (seizures). The disorder is also characterized by distinctive abnormalities of the head and facial (craniofacial) area. Such abnormalities may include an unusually small head (microcephaly) with a high forehead; an elongated face; widely spaced eyes (ocular hypertelorism); a thin upper lip; a flat nasal bridge with a prominent nasal tip; and large, low-set ears.
The symptoms and findings associated with Chromosome 14 Ring may vary in range and severity from case to case. However, in many individuals with the disorder, such abnormalities may include growth delays before and after birth (prenatal and postnatal growth retardation), diminished muscle tone (hypotonia), feeding difficulties during infancy, psychomotor delays, and mental retardation. In addition, recurrent seizures (epilepsy) typically develop beginning during infancy or early childhood. The specific form a seizure takes and its associated symptoms may vary, depending upon the region(s) of the brain affected and other factors. For example, seizure episodes may be characterized by shock-like contractions of certain muscles or muscle groups (myoclonic seizures); increased stiffness (rigidity) and rapid, rhythmic contraction and relaxation of certain muscle groups (tonic-clonic seizures); sensory or behavioral disturbances; lost consciousness; and/or impaired control of certain voluntary functions, such as bowel or bladder control. (For more information, please choose “epilepsy” as your search term in the Rare Disease Database.)
Individuals with Chromosome 14 Ring may also have characteristic abnormalities of the head and facial (craniofacial) area, resulting in a distinctive facial appearance. These abnormalities may include a small head (microcephaly) with a high forehead; an elongated face; and a flat nasal bridge with a prominent nasal tip and slightly upturned nostrils (anteverted nares). The eyes may be widely spaced (ocular hypertelorism) with downwardly slanting eyelid folds (palpebral fissures) and vertical skin folds covering the eyes’ inner corners (epicanthic folds). Affected individuals may also have additional characteristic features, such as a thin upper lip; downwardly turned corners of the mouth; a highly arched roof of the mouth (palate); an unusually small jaw (micrognathia); and large, low-set ears.
Chromosome 14 Ring may also be characterized by other physical abnormalities, including a short neck with excessive skin folds; abnormal skin ridge patterns (dermatoglyphics), such as the presence of a single crease across the palm (simian crease); widely spaced nipples; and abnormalities of skin coloration (pigmentation). These may include vitiligo, a chronic condition in which patches of skin lose pigmentation, or the presence of cafe-au-lait spots, which are light brown or pale tan discolorations of the skin. (For more information, please choose “vitiligo” as your search term in the Rare Disease Database.) Some affected individuals may also have abnormalities of the nerve-rich membrane that forms the innermost region of the eye (retina), such as abnormalities of retinal pigmentation.
In some cases, certain additional abnormalities may also be associated with Chromosome 14 Ring. For example, in addition to seizures, other neurological symptoms may sometimes be present, such as an impaired ability to coordinate voluntary movements (ataxia) or rhythmic involuntary movements of a part or parts of the body (tremor) that occur or may increase with certain goal-directed voluntary actions (intention tremor). In addition, in some affected individuals, certain joints may become permanently flexed or extended in fixed postures (joint contractures). Abnormalities of the heart may also be present at birth (congenital heart defects), such as narrowing (stenosis) of the major artery that carries oxygenated blood to the body (aorta) or the artery that transports oxygen-depleted blood to the lungs (pulmonary artery). Individuals with Chromosome 14 Ring may also be susceptible to repeated respiratory infections.
Chromosome 14 Ring results from loss (deletion) of genetic material from both ends of the 14th chromosome and joining of the ends to form a ring. Associated symptoms and findings may vary, depending upon the amount of genetic material lost from the 14th chromosome or the stability of the ring chromosome during subsequent cellular divisions (i.e., mitosis). Evidence suggests that features associated with Chromosome 14 Ring may result from relatively small deletions of genetic material from the long arm (q) of chromosome 14 (14q).
Chromosomes are found in the nucleus of all body cells. They carry the genetic characteristics of each individual. Pairs of human chromosomes are numbered from 1 through 22, with an unequal 23rd pair of X and Y chromosomes for males and two X chromosomes for females. Each chromosome has a short arm designated as “p” and a long arm identified by the letter “q.” Chromosomes are further subdivided into bands that are numbered.
Chromosome 14 Ring usually appears to be caused by spontaneous or “de novo” errors early during the development of the embryo. The parents of an affected child typically have normal chromosomes, and the probability of having another child with the chromosomal abnormality is low. However, when a parent of the affected individual has Chromosome 14 Ring, the chances are greater of having another child with this chromosomal abnormality.
Chromosome 14 Ring is an extremely rare chromosomal disorder that has appeared to affect males slightly more often than females. There have been over 40 cases reported in the medical literature.
In some cases, a diagnosis of Chromosome 14 Ring may be suggested before birth (prenatally) by specialized tests such as ultrasound, amniocentesis, and/or chorionic villus sampling (CVS). Ultrasound studies may reveal characteristic findings that suggest a chromosomal disorder or other developmental abnormalities in the fetus. During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and analyzed, while CVS involves the removal of tissue samples from a portion of the placenta. Chromosomal analysis performed on such fluid or tissue samples may reveal the presence of Chromosome 14 Ring.
The diagnosis of Chromosome 14 Ring may be confirmed after birth (postnatally) based upon a thorough clinical evaluation, characteristic physical findings, and chromosomal analysis. Specialized testing may also be conducted to detect certain findings that may be associated with the disorder. Such testing may include electroencephalography (EEG) and computerized tomography (CT) scanning or magnetic resonance imaging (MRI) of the brain. An EEG is a noninvasive diagnostic technique that records the brain's electrical activity. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of the brain's tissue structure. During MRI, a magnetic field and radio waves form detailed cross-sectional images of the brain.
The treatment of Chromosome 14 Ring 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, such as pediatricians; physicians who specialize in neurological disorders (neurologists); heart specialists (cardiologists); physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); physical therapists; and/or other health care professionals.
In some cases, treatment with antiseizure (anticonvulsant) drugs may help prevent, reduce, or control seizures associated with Chromosome 14 Ring. The specific medication used may depend upon the form of seizures present and other factors. In some affected individuals, seizures may be difficult to control (refractory). In such cases, recommended treatment may include combining certain appropriate anticonvulsant drugs.
The treatment of individuals with Chromosome 14 Ring may also include measures to help prevent or aggressively treat respiratory infections. In addition, orthopedic measures and physical therapy may be recommended to help prevent or correct contracture development. In individuals with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may be required. The surgical procedures performed may depend upon the location and severity of the abnormalities, their associated symptoms, and other factors.
Early intervention may also be important in ensuring that affected children reach their potential. Special services that may be beneficial include special education and other medical, social, and/or other services.
Genetic counseling will also be of benefit for individuals with Chromosome 14 Ring and their families. Other treatment for this disorder is symptomatic and supportive.
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