Abstract. X-linked dominant chondrodysplasia punctata, (CDPX2 – MIM ) also known as Conradi-. Hünermann-Happle syndrome, is a rare form of. X-linked chondrodysplasia punctata 2 is a disorder characterized by bone, skin, and eye abnormalities. It occurs almost exclusively in females. Although the. Minerva Pediatr. Mar;45(3) [Chondrodysplasia punctata (the Conradi-Hünermann syndrome). A clinical case report and review of the literature ].
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The specific symptoms and severity of the disorder may vary greatly from one individual to another. The disorder can cause serious complications at birth or be so mild that individuals may not be identified until adulthood usually after having an affected child. It is important to note that affected individuals may not have all hujermann the symptoms discussed below. Affected individuals should talk to their physician and medical team about their specific case, associated symptoms and overall prognosis.
Intelligence is usually unaffected. Affected infants may fail to grow and gain weight at the rate expected for age and gender failure to thrive. Growth deficiencies may ultimately result in a final adult height that is below normal short stature. Some affected infants are prone to developing repeated infections.
Cartilage is a tough, elastic type of connective tissue that provides cushion and structure within the body. When the skeleton begins to develop, it predominately consists syndrime cartilage, which is gradually replaced by bone.
The development of these abnormal calcified syndrme may also be known as chondrodysplasia punctata. Chondrodysplasia punctata tends to resolve on its own within the first few years of life.
Such features commonly include asymmetric shortening of long bones of the limbs, particularly those of the upper arms humeri and the thigh bones femoracausing disproportionate length of the arms and legs with one side typically more affected than the other. Affected individuals also frequently have abnormal sideways and, in some cases, front-to-back curvature of the spine scoliosis or kyphoscoliosis.
Abnormal stiffness of the joints or joints that are fixed or locked in a bent position flexion contractures may also occur. Cataracts may be present at birth congenital or may develop during infancy. Cataracts may affect one or both eyes. Cataracts can caused blurred vision or decreased clarity of vision. In rare cases, additional eye ocular abnormalities include abnormally small eyes microphthalmosabnormally small corneas microcorneadown-slanting eyelid folds palpebral fissuresrapid, involuntary eye movements nystagmusand degeneration of the main nerve that transmits nerve impulses from the retina to the brain optic atrophy.
In some cases, eye abnormalities can significantly reduce vision. Additional distinctive facial features may occur in some cases including an unusually huhermann forehead frontal bossingocnradi cheekbones malar hypoplasiaa flattened bridge of the nose, upturned nostrils anteverted nares and malformed dysplastic ears.
Hearing loss has been reported in some cases. In the newborn period, many affected infants also have redness erythema and unusual thickening, dryness, and scaling of the skin ichthyosiform erythroderma distributed in a linear, blotchy pattern over the body. Although the eruption usually resolves during infancy, older children may subsequently develop inflammation and wasting atrophy of follicles follicular atrophodermacausing pores to appear unusually large.
In some cases, affected areas of the skin may be darker or lighter than sjndrome areas hyper- and hypopigmentation. Patchy areas of hair loss and scarring may develop on the scalp cicatricial alopecia. The sparse scalp hair may also be unusually coarse and lusterless. In many cases, this mutation occurs randomly, for no apparent reason i. The gene mutation is inherited as an X-linked dominant trait. Genetic diseases are determined by the combination of genes for a particular trait that are on the chromosomes received from the father and the mother.
X-linked dominant disorders are conditions caused by an abnormal gene on the X chromosome.
Females have two X chromosomes, whereas males have one X chromosome and one Y 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. According to researchers, in males who inherit a disease gene for an X-linked dominant disorder hemizygotesit is suspected that full expression of the disorder may be associated with loss of life before birth.
Men with a disease gene for an X-linked disorder transmit the gene to their daughters but not to their sons. Women with a copy of the disease gene have a 50 percent risk of transmitting the gene to their daughters and their sons.
Investigators have determined that the EBP gene is located on the short arm p of the X chromosome Xp Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual.
Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Chromosomes are further sub-divided into many bands that are numbered. The numbered bands specify the location of the thousands of genes that are present on each chromosome. The EBP gene creates a protein known as emopamil-binding protein. Mutations of the Cohradi gene result in deficient levels of functional copies of this protein.
Emopamil-binding protein functions as a sterolisomerase enzyme and plays a role in cholesterol biosynthesis. Biosynthesis is the building or conversion of complex chemical compounds from simple substances in the body. Such cases include rare instances in which more than one child of apparently unaffected parents have the disorder.
Gonadal mosaicism may be suspected when apparently unaffected parents have more than one child with the same genetic abnormality. Within families, there is variation in the severity of the clinical picture between affected females, and this is largely secondary to differences in X-inactivation.
The exact incidence of the disorder in the general population is unknown, although one estimate places it at 1 inindividuals. The disorder is often apparent at birth congenitalbut some individuals with mild cases may not be indentified until adulthood.
Chondrodysplasia punctata was first described in the medical literature by Drs. Comparisons may be useful for a differential diagnosis.
Rhizomelic chondrodysplasia punctata RCDP spectrum are a group of rare disorders that are also classified as peroxisomal biogenesis disorders. RCDP is characterized by bilateral and symmetric shortening of the upper long bone of the arms humerus and legs femura condition known as rhizomelia. Additional findings include distinctive facial features, the formation of small, hardened spots of calcium stippling on the knee cap patella and long bones of the arms and legs chondrodysplasia punctatacataracts that are present at birth or shortly thereafter, profound growth deficiency after birth, mental retardation, and seizures.
RCDP causes life-threatening complications during the first decade of life and in some cases during the newborn neonatal period.
Milder forms of RCDP have been identified in which affected individuals have less severe mental deficits and growth deficiency and often no rhizomelia.
Many of these disorders are caused by mutations in the PEX7 gene and are inherited as an autosomal recessive trait. Chondrodysplasia punctata, X-linked recessive type, is a form of chondrodysplasia punctata characterized by abnormal, symmetric, dotlike punctate calcifications within the growing ends of certain long bones i.
Additional characteristic findings may include sparse, unruly hair; ichthyosis, primarily over the neck, on the chest, under the arms, and on the backs of the legs; and underdevelopment of the nose nasal hypoplasia.
Conradi–Hünermann syndrome – Wikipedia
The severity of the disorder can vary greatly from one person to another. Because the disorder is inherited as an X-linked recessive trait, it is typically fully expressed in males only. The disorder is caused by deletions or chromosomal rearrangements translocations involving the end of the short arm p of chromosome X Xp A gene mapped to this chromosomal region regulates production of an enzyme known as arylsulfatase Humermann ARSE.
Enzymes are proteins that conradj the rate of certain chemical reactions in the body. Mutations of this gene have been identified in several individuals with the disorder, suggesting that altered ARSE activity plays a causative role in the development of X-linked recessive chondrodysplasia punctata.
Rare Disease Database
CHILD syndrome, a rare genetic disorder that is apparent at birth congenital cknradi, is characterized by distinctive skin abnormalities and limb defects affecting one side of the body hemidysplasia. According to investigators, some cases of eyndrome disorder appear to result from different mutations of the same gene i. The gene encodes a steroid dehydrogenase enzyme that also plays a role in cholesterol metabolism.
Fetal warfarin syndrome, which may also be referred to as coumarin embryopathy, is a characteristic pattern of birth defects in a newborn resulting from exposure to certain anticlotting drugs i. Evidence suggests that the greatest period of risk occurs from approximately six to nine weeks following conception. These disorders include Zellweger spectrum hunerman, Smith-Lemli-Optiz syndrome, fetal alcohol syndrome, trisomies 18 and 12, Greenberg dysplasia, and chondrodysplasia punctata, tibia-metacarpal type.
These disorders include other forms of ichthyosis. For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.
Humermann evaluation may reveal characteristic stippling of epiphyses and syndroem regions of the cartilaginous skeleton. However, as noted above, there is loss of distinctive epiphyseal stippling over time, potentially making diagnosis difficult.
In addition, there have been instances in which individuals with only mild manifestations have not been identified until adulthood. Mutations of the EBP gene result in the accumulation of sterols in the plasma and certain tissues of the body. Sterol levels are measured by gas chromatography-mass spectrometry. Various orthopedic measures, including surgery, may be recommended to help prevent, treat, or correct certain skeletal abnormalities associated with the disorder.
Surgery may also be advised hundrmann certain craniofacial malformations, scoliosis or other physical abnormalities. The surgical procedures performed will depend on the nature, severity, and combination of anatomical abnormalities, their associated symptoms, and other factors.
Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive. Information on current clinical trials is posted on the Internet conrdi www.
All studies receiving U. Elsevier Saunders, Philadelphia, PA; New York, NY; Syndromes of the Head and Neck. X-linked dominant chondrodysplasia punctata CDPX2 caused by single gene mosaicism in a male. Am J Med Genet.
Has C, Bruckner-Tuderman L, et al. Whittock NV, Izatt L. X-linked Dominant Chondrodysplasia Punctata.
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