NORD gratefully acknowledges Almuth Caliebe, MD, Institute of Human Genetics, University Hospital Schleswig-Holstein, Campus Kiel & Christian-Albrechts-University Kiel, Kiel, Germany, for assistance in the preparation of this report.
Catel-Manzke syndrome is a rare genetic disorder characterized by distinctive abnormalities of the index fingers and the classic features of Pierre Robin sequence. Affected individuals have an extra bone at the base of the index that causes the index fingers to be locked in a bent position (clinodactyly). Pierre Robin sequence refers to abnormalities that may occur as a distinct syndrome or as part of another underlying disorder. Pierre Robin sequence 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). A variety of additional physical findings can also be present. The specific symptoms can vary from one person to another. Alterations (mutations) in the TGDS gene have been identified in individuals with Catel-Manzke syndrome.Introduction
Catel-Manzke syndrome was first described in the medical literature in 1961 by Dr. Catel and later further evaluated by Dr. Manzke in 1966. The disorder was originally referred to as a palatodigital syndrome, but because cleft palate does not always occur, Dr. Manzke suggested replacing palatodigital syndrome with micrognathia-digital syndrome.
Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disorder prevent physicians from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all of the symptoms discussed below. Parents should talk to their children’s physician and medical team about their specific case, associated symptoms and overall prognosis.
Infants with Catel-Manzke syndrome have an extra (supernumerary), irregularly-shaped bone (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 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. Consequently, the index fingers may be fixed in an abnormally bent position (clinodactyly). These distinctive findings of the index fingers may be known as Manzke dysostosis.
In many cases, affected individuals also have the three findings of Pierre-Robin sequence including an unusually small jaw (micrognathia), downward displacement or retraction of the tongue (glossoptosis), and incomplete closure of the roof of the mouth (cleft palate). However, cleft palate is not always present and a few cases none of the features of Pierre-Robin sequence develop. Individuals with micrognathia and glossoptosis may have feeding and breathing difficulties resulting in growth deficiency and failure to thrive.
In addition, some infants with the syndrome may have structural abnormalities of the heart that are present at birth (congenital heart defects), mostly commonly ventricular or atrial septal defects. Better known as “a hole in the heart” these defects occur when there is a hole in the wall (septum) separating the two upper chambers (ventricles) of the heart from each other or in the septum separating the two lower chambers (atria) from each other.
Less often, 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); adducted thumbs; and/or a single deep crease across the palms of the hands.
Affected individuals may also have distinctive facial features including eyes that are spaced apart wider than usual (hypertelorism), full cheeks, low-set ears, thin eyebrows, narrow nostrils, and a cleft or area of missing tissue in the colored portion of the eye (iris coloboma). Additional skeletal abnormalities may occur including abnormal curvature of the spine (scoliosis), an unusually prominent or sunken breastbone (pectus carinatum or pectus excavatum), short big toes (short halluces), clubfoot (talipes equinovarus), looseness (laxity) of certain joints, and dislocation of the joints, such as dislocation of the knees.
Some children may experience delays is reaching developmental milestones. Mild-to-moderate intellectual disability and has been reported in few individuals, although in the majority of affected individual intelligence is not affected.
Alterations (mutations) in the TGDS gene have been identified in individuals with Catel-Manzke syndrome. Genes provide instructions for creating proteins that play a critical role in many functions of the body. When a mutation of a gene occurs, the protein product may be faulty, inefficient, or absent. Depending upon the functions of the particular protein, this can affect many organ systems of the body.
The TGDS gene is located on the long arm (q) of chromosome 13 (13q32.1). Chromosomes are located in the nucleus of human cells and carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes numbered from 1 through 22 are called autosomes and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 13q32.1” refers to band 32.1 on the long arm of chromosome 13. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Researchers believe that, at least in some individuals, Catel-Manzke syndrome may be inherited as an autosomal recessive trait. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits 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 likelihood for two carrier parents to both pass the altered gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents is 25%. The risk is the same for males and females.
The incidence and prevalence of Catel-Manzke syndrome is unknown. More than 33 individuals with the disorder have been reported in the medical literature. Since some individuals may go misdiagnosed or undiagnosed, determining the true frequency of Catel-Manzke syndrome in the general population is difficult. More males have been described with the disorder than females, but this may be a coincidence since so few individuals have been reported in the medical literature.
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.).
Clinical Testing and Workup
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 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 specialists. Pediatricians, orthopedists, craniofacial surgeons, cardiologists, speech therapists, and other healthcare professionals may need to systematically and comprehensively plan an affect child’s treatment. Genetic counseling may be of benefit for affected individuals and their families. Psychosocial support for the entire family is essential as well.
There are no standardized treatment protocols or guidelines for affected individuals. Due to the rarity of the disease, there are no treatment trials that have been tested on a large group of patients. Various treatments have been reported in the medical literature as part of single case reports or small series of patients. Treatment trials would be very helpful to determine the long-term safety and effectiveness of specific medications and treatments for individuals with Catel-Manzke syndrome.
Specific therapies for the treatment of Catel-Manzke syndrome are symptomatic and supportive. For infants with feeding and respiratory difficulties recommended disease management may include keeping infants on their stomachs (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).
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.
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.
For infants and children with congenital heart defects, treatment with certain medications, surgical intervention, and/or other measures may also be required. 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.
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:
Toll-free: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, in the main, contact:
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., Pierre Robin syndrome, congenital heart defects, etc.].)
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