Aase syndrome is a rare genetic disorder that may be detected during early infancy. The disorder is primarily characterized by the presence of three bones (phalanges) within the thumbs (triphalangeal thumbs) rather than the normal two and abnormally reduced production of red blood cells (hypoplastic anemia). In some instances, additional abnormalities may be present. The exact cause of Aase syndrome is unknown. However, most evidence suggests that the disorder is inherited as an autosomal recessive trait.
The primary findings associated with Aase syndrome include deficiency of red blood cells at birth (congenital hypoplastic anemia) and distinctive malformations of the thumbs.
Infants with the disorder typically have moderate to severe reductions in the level of oxygen-carrying red blood cells (anemia). The condition is due to deficiency of certain bone marrow cells (i.e., red cell precursors) involved in the production of red blood cells (erythrocytes). (The bone marrow is the specialized tissue within the cavities of certain bones. Red bone marrow plays an essential role in the production and maturation of red blood cells as well as certain white blood cells and platelets.) Infants with congenital hypoplastic anemia develop abnormal paleness of the skin (pallor). Additional findings may include mild growth delays, weakness, and other associated abnormalities. In addition, if treatment requires repeated blood transfusions, affected individuals may develop abnormal enlargement of the liver and spleen (hepatosplenomegaly) with reduced levels of platelets in the blood (secondary thrombocytopenia), increased deposition of iron within various tissues (hemosiderosis); and/or other findings. (For further information, please see the “Standard Therapies” section of this report below.) According to reports in the medical literature, the anemia associated with Aase syndrome may tend to improve with age.
As mentioned above, infants with Aase syndrome also have characteristic malformations of the thumbs. The relatively small bones that comprise the skeleton of the fingers and thumbs are known as “phalanges.” The thumbs normally have two phalanges, whereas the fingers contain three. However, Aase syndrome is characterized by the presence of three phalanges within the thumbs (triphalangism), with underdevelopment of the thumb muscles (i.e., thenar muscles). Due to such abnormalities, the thumbs have sometimes been described as “finger like” in appearance. In addition, in some affected individuals, there may be mild underdevelopment or shortness of the bones (i.e., radii) on the outer or thumb side of the forearms (radial hypoplasia).
Some affected individuals may have additional skeletal abnormalities. These may include improper development (dysplasia) of the middle bone within the fifth fingers or “pinkies”; absence (agenesis) of the collarbones (clavicles); and/or unusually narrow, sloping shoulders. In addition, some affected individuals may have 11 rather than the normal 12 rib pairs; malformations of certain bones of the spinal column (vertebral defects), underdevelopment of the ilia, which are the uppermost of the three bones forming the hipbones, and/or other skeletal abnormalities.
In some instances, infants and children with Aase syndrome may also have abnormalities of the skull and facial (craniofacial) region. For example, there may be late closure of the “soft spots” or the membrane-covered gaps (fontanels) that are present between bones of the skull at birth. Additional craniofacial abnormalities may include incomplete closure of the roof of the mouth (cleft palate); an abnormal groove in the upper lip (cleft lip), downslanting eyelid folds (palpebral fissures), and/or an unusually short, webbed neck.
In some individuals with Aase syndrome, additional abnormalities may also be present, such as mental retardation; abnormal skin pigmentation, and/or a congenital heart defect known as a ventricular septal defect (VSD). VSD is characterized by an abnormal opening in the fibrous partition (septum) that divides the two lower chambers (ventricles) of the heart.
Some experts have questioned whether Aase syndrome is in fact a distinctive disease entity, suggesting that the disorder may be a variant of Blackfan-Diamond anemia. Such researchers indicate that triphalangeal thumbs as well as additional congenital malformations seen in Aase syndrome have also been reported in some individuals with Blackfan-Diamond anemia. (For further information on this disorder, please see the “Related Disorders” section of this report below.)
Although the exact cause of Aase syndrome is unknown, most evidence suggests that the disorder is inherited as an autosomal recessive trait. 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 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.
Aase syndrome appears to affect males and females equally. The disorder was originally described in two brothers in 1969 (Aase JM). Approximately 20 cases have been recorded in the medical literature.
In most individuals with Aase syndrome, the diagnosis may be made during early infancy based upon a thorough clinical examination, identification of characteristic physical findings, and a variety of specialized tests. Such testing may include laboratory analyses, such as certain blood, enzyme, and bone marrow studies, to confirm congenital hypoplastic anemia. In addition, advanced imaging techniques (e.g., computed tomography [CT] scanning, magnetic resonance imaging [MRI]) or other diagnostic tests may be conducted to detect and characterize skeletal or other abnormalities that may be associated with the disorder. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. During MRI, a magnetic field and radio waves create detailed cross-sectional images of certain organs and tissues.
The treatment of Aase 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, such as pediatricians; specialists in the study of the blood and blood-forming tissues (hematologists), physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); surgeons; and/or other health care professionals.
Anemia associated with Aase syndrome often responds to corticosteroid therapy, such as treatment with prednisone. In addition, according to reports in the literature, some affected individuals who received prednisone therapy have achieved an apparent, permanent cessation of the anemia (remission). In other cases, there may be an inadequate response to corticosteroid therapy, necessitating periodic blood transfusions. As mentioned above, those who receive repeated transfusions may develop abnormal enlargement of the liver and spleen (hepatosplenomegaly), abnormally reduced levels of platelets in the blood (secondary thrombocytopenia), excessive deposits of iron within various tissues (hemosiderosis), and/or other complications. In such cases, additional supportive measures may be required, such as administration of certain agents (chelating agents) that may bind to iron, enabling it to be excreted from the body. In some cases, other measures may be recommended for those with anemia that is unresponsive to corticosteroid therapy.
In some instances, corrective and reconstructive surgery may be recommended to help correct certain craniofacial malformations, skeletal defects, and/or other physical abnormalities potentially associated with the disorder. The surgical procedures performed will depend upon the severity and location of the anatomical abnormalities, their associated symptoms, and other factors.
Early intervention may be important to ensure that children with Aase syndrome reach their potential. Special services that may be beneficial include special education and/or other medical, social, 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.
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Online Mendelian Inheritance in Man, OMIM (TM). John Hopkins University, Baltimore, MD. MIM Number 205600; 7/3/97. Available at: http://www.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?205600.