Description
Conradi-Hünermann syndrome is a rare X-linked dominant genetic disorder. It is classified as a form of chondrodysplasia punctata . It affects females almost exclusively, although rare cases in which males were affected have been reported. Conradi-Hünermann syndrome is characterized by short stature, skeletal malformations skin abnormalities, and cataracts. It is also commonly associated with disproportionate and asymmetric shortening of long bones, upper arms and thigh bones to be specific, curvature of the spine, and mild to moderate growth deficiency that leads to short stature. Affected females have typically normal intelligence and life expectancy; however, it is life threatening and much more severe in males. Affected males suffer from weak muscle tone, changes in the structure of the brain, moderate to severe delay in development, seizures, distinctive facial features, and other birth defects. It is now proven that the disease is due to a genetic mutation.
Prevalence
The exact incidence of Conradi-Hünermann syndrome is unknown; however, it is estimated to be around 1/200,000-400,000 with about 95% of cases occurring in females. Nonetheless, the disorder might actually be more common than this estimate because it is believed to be underdiagnosed, particularly in females with milder symptoms.
Causes
It is believed that a mutation in (EBP) gene that is random and for no apparent reason in many cases is the main cause of this condition. This gene provides instructions for making an enzyme called 3β-hydroxysteroid-Δ8,Δ7-isomerase. This enzyme is responsible for last steps of cholesterol biosynthesis. Mutations in EBP gene leads to deficiency in number of functional copies of the protein and therefore, reduced activity of 3β-hydroxysteroid-Δ8,Δ7-isomerase. The shortage of this enzyme causes a buildup of potentially toxic by-products of cholesterol production in the body. It is believed that the clinical features of the syndrome is due to a combination of low cholesterol levels as well as accumulation of this toxic by-products that together, disrupt the growth and development of various body systems.
Symptoms
The extent of symptoms of Conradi-Hünermann syndrome differs from person to person. It can result in very serious complications or have symptoms that are so low that the individual doesn’t even notice them until adulthood. Conradi-Hünermann syndrome patients usually have short stature that is a result of growth deficiency during childhood. There are several musculoskeletal abnormalities accompanied by the syndrome including asymmetric shortening of long bones of the limbs, particularly those of the upper arms (humeri) and the thigh bones (femora), front to back curvature of the spine (Scoliosis that in many cases is non-idiopathic), and abnormal stiffness of joints or even joints that are locked in bent positions. Flat face, low nasal bridge, Down-slanting space between eyelids, upturned nostrils, and malformed ears are among facial features. Ocular symptoms also include cataracts or clouding of the lenses of the eye. This might be present at birth or develop later during infancy. Some babies suffering from Conradi-Hünermann syndrome have redness, unusual thickening and scaling of the skin. However, intelligence is typically normal except for a few cases in male patients where moderate to profound delayed development, seizures, hypoplasia, and agencies of corpus callosum was reported.
Diagnosis
No specific diagnostic criteria has been described for Conradi-Hünermann syndrome. However, a diagnosis of Conradi-Hünermann syndrome is typically based upon clinical, biochemical, and genetic tests as well as identification of characteristic symptoms, and a thorough patient history. Stippling of epiphyses and other regions of the cartilage bone is a characteristic symptom and a main diagnostic criterion. Nonetheless, this distinctive epiphyseal stippling is lost over time, making it harder to diagnose the condition in adults. Also, if biochemical analysis shows elevated levels of 8(9)-cholestenol and 8-dehydrocholesterol, the possibility of this syndrome is raised. Additionally, a test to measure levels of sterols in plasma can be done to confirm the results; because mutations in EBP gene results in accumulation of sterols in plasma and certain tissues. A diagnosis of Conradi-Hünermann syndrome can be confirmed by identification of characteristic genetic mutation that cause Conradi-Hünermann syndrome through genetic molecular testing.
Diagnostic tests
A few tests may be used to diagnose Conradi-Hünermann syndrome. Sterol analysis of plasma, scales from skin lesions, or cultured lymphoblasts or fibroblasts are main tests that can help diagnose the syndrome. Increased concentration of 8(9)-cholestenol and 8-dehydrocholesterol (0.18—186 μg/mL and <0.01—138 μg/mL respectively) are indications of this condition. Also molecular genetic testing such as sequence analysis or mutation scanning can be used to identify a mutation in EBP gene.
Treatment
Treatment and management of Conradi-Hünermann is often symptomatic and individualized. To help, prevent, or correct certain skeletal malformation, orthopedic measures and surgeries are recommended. Also for craniofacial malformations, scoliosis or other physical abnormalities surgery might be advised. Ocular management is also usually requires. Early surgical removal of cataracts, implanting artificial lenses or other corrective devices are examples of that. Dermatological problems may be managed by the use of emollients and keratolytics (i.e. ammonium lactate 12%, petrolatum ointment). Also, it might be beneficial to administrate lovastatin and cholesterol to treat ichthyosis. In other cases Physical, occupational, and speech therapies might be necessary. There are also Standard interventions for congenital heart defects, kidney anomalies, and hearing loss
Prognosis
Typically life expectancy of female patients is not affected unless severe scoliosis has com promised lung and heart function. However, males usually can’t survive infancy or early childhood. In both genders quality of life may be severely affected by symptoms of the condition.
Tips for living
Find a support group online. Internet is a good place to get to know real life people who are going through the same thing as you. Facebook is a good place to start.