Catel-Manzke syndrome is a rare genetic disorder characterized by distinctive abnormalities of the index fingers; the classic features of Pierre Robin syndrome; and, in some cases, additional physical findings. Pierre Robin syndrome refers to a sequence of abnormalities that may occur as a distinct syndrome or as part of another underlying disorder. Pierre Robin syndrome is characterized by an unusually small jaw (micrognathia), downward displacement or retraction of the tongue (glossoptosis), and incomplete closure of the roof of the mouth (cleft palate).
Infants with Catel-Manzke syndrome have an extra (supernumerary), irregularly shaped bone (i.e., hyperphalangy) located between the first bone of the index finger (proximal phalanx) and the corresponding bone within the body of the hand (second metacarpal). As a result, the index fingers may be fixed in an abnormally bent position (clinodactyly). In some cases, additional abnormalities of the hands may also be present. Due to the presence of micrognathia, glossoptosis, and cleft palate, affected infants may have feeding and breathing difficulties; growth deficiency; repeated middle ear infections (otitis media); and/or other complications. In addition, some infants with the syndrome may have structural abnormalities of the heart that are present at birth (congenital heart defects). The range and severity of symptoms and findings may vary from case to case. Catel-Manzke syndrome usually appears to occur randomly, for unknown reasons (sporadically).
As noted above, the range and severity of associated features may be variable from case to case. However, characteristic abnormalities often include malformations of the index fingers; additional skeletal defects; and Pierre Robin syndrome or the association of a small jaw (micrognathia) and clefting or incomplete closure of the palate, often with downward displacement or retraction of the tongue (glossoptosis).
Catel-Manzke syndrome is characteristically associated with “hyperphalangy”–or the presence of an extra bone (phalanx)–of the index finger. This accessory, irregularly shaped bone is located between the abnormally shortened first bone (proximal phalanx) of the index finger and the corresponding bone in the middle of the hand (i.e., second metacarpal). As a result, the lower part of the index finger may bend toward the thumb and the upper part may bend toward the pinky. Eventually, the extra bone may fuse with the proximal phalanx and second metacarpal.
Some affected infants may also have additional abnormalities of the hands. Such malformations may include abnormal bending or deviation (clinodactyly) of the “pinkies” or fifth fingers; abnormal division of the first bone of the middle of the hand (bifurcated first metacarpal); and/or a single deep crease across the palms of the hands (simian creases). In addition, in up to 30 percent of reported cases, affected infants have a deformity in which the foot is abnormally twisted out of shape or position (clubfoot), with the heel of the foot turned inward and the sole flexed [i.e., talipes equinovarus]).
In some cases, Catel-Manzke syndrome may also be characterized by additional skeletal defects. These may include abnormalities of certain bones of the spinal column (vertebrae), rib anomalies, an unusually prominent or sunken breastbone (pectus carinatum or pectus excavatum), easily dislocatable knees, and/or other abnormalities.
The association of micrognathia, glossoptosis, and cleft palate (i.e., Pierre Robin syndrome) may result in an increased risk of repeated middle ear infections (otitis media) and associated hearing impairment; feeding difficulties; and breathing difficulties in the newborn period. Associated abnormalities may include impaired sucking and swallowing; failure to grow and gain weight at the expected rate (failure to thrive); upper airway obstruction; episodes in which there is sudden absence of spontaneous breathing (apnea); insufficient oxygen supply to body tissues (hypoxia); and/or potential, associated developmental impairment. However, in most reported cases, affected individuals have had normal intelligence.
In addition to the features of Pierre Robin syndrome, some affected infants may have additional abnormalities of the skull and facial (craniofacial) region. Such craniofacial features may include an unusually round or globular skull (cranium); an abnormal groove in the upper lip (cleft lip); low-set, malformed ears; prominent, widely set eyes (ocular hypertelorism); vertical skin folds that may cover the eyes’ inner corners (epicanthal folds); a short neck; and/or other abnormalities.
In approximately 40 to 50 percent of cases, infants with Catel-Manzke syndrome may also have various congenital heart (cardiac) defects, primarily ventricular septal defects (VSDs). A VSD is an abnormal opening in the partition (septum) that separates the two lower chambers (ventricles) of the heart, allowing some oxygen-rich blood to recirculate through the lungs and potentially leading to rising blood pressure in the lungs’ blood vessels (pulmonary hypertension). Associated symptoms and findings may vary, depending on the size, location, and nature of the defect and other factors. For example, in some cases, such as those with small isolated VSDs, no symptoms may be apparent (asymptomatic). However, in other instances, such as those with larger VSDs, associated symptoms and findings may include difficulties feeding, poor growth, difficult or labored breathing (dyspnea), profuse sweating, increased susceptibility to respiratory infections, impaired ability of the heart to pump blood efficiently to the lungs and the rest of the body (heart failure), enlargement of the heart, and/or other abnormalities. In severe cases, congenital heart disease and/or respiratory difficulties associated with Pierre Robin syndrome may lead to potentially life-threatening complications during infancy.
Catel-Manzke syndrome usually appears to occur randomly, for unknown reasons (sporadically). However, more than one affected family member has been reported in a few cases. According to some researchers, such apparently familial cases appear to suggest X-linked recessive inheritance. However, other investigators indicate that there is little evidence for X-linked recessive disease transmission, since five female cases have been recorded. (For more, see “Affected Population” below.)
X-linked recessive disorders are conditions that result from changes (mutations) of a gene on the X chromosome. Females have two X chromosomes, while males have one X chromosome from the mother and one Y chromosome from the father. In females, certain disease traits on the X chromosome may in some cases be “masked” by the normal gene on the other X chromosome. However, since males have only one X chromosome, if they inherit a gene for a disease present on the X, it is more likely to be fully expressed. Men with a disease gene for an X-linked disorder transmit the gene to their daughters, who are carriers, but not to their sons. Women with a copy of the disease gene have a 50 percent risk of transmitting the carrier condition to their daughters and a 50 percent risk of transmitting the disease to their sons. Thus, in summary, diseases that are inherited as X-linked recessive traits are usually fully expressed in males only.
Catel-Manzke syndrome is named for two investigators who originally described the disease entity (i.e., Catel W; Manzke VH). The syndrome was originally reported in a patient in 1961 (Catel) who was later reevaluated in 1966 (Manzke). Approximately 25 cases have been documented, mostly in male individuals. Five female cases have been recorded, including two sisters.
In some cases, Catel-Manzke syndrome may be suspected before birth (prenatally) based upon advanced imaging techniques such as ultrasound. In fetal ultrasonography, reflected sound waves may be used to create an image of the developing fetus, potentially revealing certain findings suggestive of Catel-Manzke syndrome (e.g., abnormal smallness of the jaw, malformation of the index fingers, etc.).
In most cases, Catel-Manzke syndrome is diagnosed at birth based upon a thorough clinical evaluation, identification of characteristic physical findings (e.g., micrognathia, cleft palate, abnormalities of the index fingers, etc.), and/or imaging tests. For example, imaging tests may elaborate distinctive abnormalities affecting the fingers, particularly the index fingers. In addition, x-ray studies may also confirm and/or reveal the extent of micrognathia, skeletal malformations, and/or additional abnormalities.
Congenital heart defects that may occur in association with Catel-Manzke syndrome (e.g., ventricular septal defects) may be detected and/or characterized by a thorough clinical examination, evaluation of heart and lung sounds through use of a stethoscope, and specialized tests that enable physicians to evaluate the structure and function of the heart (e.g., x-ray studies, electrocardiogram [EKG], echocardiogram). An EKG, which records the heart's electrical impulses, may reveal abnormal electrical patterns. During an echocardiogram, reflected high-frequency sound waves are used to obtain an image of the heart, enabling physicians to study cardiac structure and motion.
The treatment of Catel-Manzke syndrome is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; surgeons; heart specialists (cardiologists); physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); speech pathologists; physical therapists; and/or other health care professionals.
Specific therapies for the treatment of Catel-Manzke syndrome are symptomatic and supportive. For infants with feeding and respiratory difficulties (e.g., due to micrognathia, glossoptosis, cleft palate [Pierre Robin syndrome]), recommended disease management may include keeping infants on their stomaches (prone positioning) and monitoring of breathing. In some cases, treatment may also require placement of a breathing tube or, if necessary, the performance of certain surgical procedures. Such measures may include a procedure in which the tongue is temporarily joined to the lower lip (tongue-lip adhesion) to keep the tongue from blocking the airway or creation of an opening through the neck into the windpipe into which a tube is inserted (tracheostomy). Additional supportive measures may also be required to help improve feeding and ensure sufficient intake of nutrients, such as the use of modified artificial nipples or, in some cases, tube feeding (gavage feeding). In addition, surgical measures to correct cleft palate will be advised at the appropriate age during infancy or childhood in order to repair the abnormality and to help improve speech development. Physicians may also recommend surgical correction of additional, associated craniofacial malformations in some cases.
For infants and children with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may also be required. In addition, in some cases, physicians may advise surgical repair or correction of finger (digital) malformations, additional skeletal defects, and/or other abnormalities associated with the syndrome. The specific surgical procedures performed will depend upon the size, nature, severity, and/or combination of the anatomical 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, speech therapy, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for affected individuals and their families. Other treatment for this disorder is symptomatic and supportive.
Research on genetic disorders 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 and familial disorders in the future.
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Online Mendelian Inheritance In Man(OMIM). Victor A. McKusick, Editor; Johns Hopkins University, Last Edit Date 11/18/98. Entry Number 302380.