Juberg-Marsidi syndrome is an extremely rare X-linked genetic disorder that is fully expressed in males only, and is apparent at birth (congenital) or during the first few weeks of life (neonatal period). Affected children exhibit severe mental retardation; delays in reaching developmental milestones (e.g., crawling, walking, etc.); muscle weakness; diminished muscle tone (hypotonia); and/or delayed bone growth as well as growth retardation, resulting in short stature.
Affected infants also exhibit hearing loss; underdevelopment of the genitals (microgenitalism); and/or abnormalities of the head and facial (craniofacial) area such as an abnormally small head (microcephaly), a flat (depressed) nasal bridge, eye (ocular) abnormalities, and/or, in some cases, additional physical abnormalities. The range and severity of symptoms may vary from case to case. Juberg-Marsidi syndrome is inherited as an X-linked recessive trait.
Juberg-Marsidi syndrome, an extremely rare inherited disorder, may be apparent at birth (congenital) or during the first few weeks of life (neonatal period). The physical findings and symptoms associated with Juberg-Marsidi syndrome are fully expressed in males only, and the range and severity of such symptoms may vary from case to case. However, some females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder.
In affected males, the primary findings associated with Juberg-Marsidi syndrome are severe mental retardation; hearing loss often resulting in deafness; and/or abnormalities of the genitals such as an abnormally small penis (micropenis) and/or a poorly developed (rudimentary) scrotum into which the testicles may fail to descend (cryptorchidism).
In addition to severe mental retardation, affected males may exhibit delays in reaching developmental milestones (e.g., crawling, sitting, walking, etc.) and/or delayed bone growth as well as growth retardation, resulting in short stature. Affected infants may also exhibit muscle weakness and diminished muscle tone (hypotonia) as well as muscle stiffness and uncontrolled involuntary muscle movements (spasticity). Some affected individuals may be unable to walk.
In addition, affected individuals may have a low birth weight and exhibit malformations of the head and facial (craniofacial) area such as an abnormally small head (microcephaly) with a flat (depressed) nasal bridge and/or abnormalities of the eyes (ocular) such as crossed eyes (strabismus). Due to hearing impairment and developmental delays, some affected individuals may have difficulty talking or be unable to speak.
In some cases, males with Juberg-Marsidi syndrome may also exhibit additional physical abnormalities. For example, in some cases, affected males may have malformed and discolored fingernails and/or toenails (onychodystrophy). In addition, some may also exhibit convulsive seizures.
Females who carry a single copy of the disease gene for Juberg-Marsidi syndrome (heterozygotes) may exhibit some of the symptoms associated with the disorder. Such heterozygous females may exhibit abnormally low intelligence and/or an abnormally small head (microcephaly).
In affected males, the primary findings associated with Juberg-Marsidi syndrome include:
Head and Neck:
A smaller than normal head (microcephaly) combined usually with underdevelopment of the region about the nose and mouth (midfacial hypoplasia).
Widely spaced eyes (telecanthus), a fold of the eyelid at the inner edge (epicanthic fold).
A small triangular nose with prominent upward pointed nostrils and a flat bridge.
A broad mouth with a large tongue that often protrudes; Abnormally located and developed teeth may also be present.
Flaccid, weak muscles from the time of birth (neonatal hypotonia).
The scrotum is undeveloped and small associated with undescended or very small testicles and, not infrequently, with a small penis.
Growth and Development:
Short stature is common as is mental retardation.
Failure to thrive as an infant; Deafness due to nerve damage or underdevelopment of the nerves in the ear.
Juberg-Marsidi syndrome is inherited as an X-linked recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.
X-linked recessive genetic disorders are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. Males have one X chromosome and if they inherit an X chromosome that contains a disease gene, they will develop the disease. Males with X-linked disorders pass the disease gene to all of their daughters, who will be carriers. Males can not pass an X-linked gene to their sons because males always pass their Y chromosome instead of their X chromosome to male offspring. Female carriers of an X-linked disorder have a 25 percent chance with each pregnancy to have a carrier daughter like themselves, a 25 percent chance to have a non-carrier daughter, a 25 percent to have a son affected with the disease, and a 25 percent chance to have an unaffected son.
In some females who inherit a single copy of the disease gene for Juberg-Marsidi syndrome (heterozygotes), disease traits on the X chromosome may not always be masked by the normal gene on the other X chromosome. As a result, these females may exhibit some of the symptoms associated with the disorder.
The gene that is believed to be involved in Juberg-Marsidi syndrome is located on the long arm (q) of the X chromosome (Xq13). 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. 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 Xq13” refers to band 13 on the long arm of the X-chromosome. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Juberg-Marsidi syndrome is an extremely rare inherited disorder that is fully expressed in males only. However, females who carry a single copy of the disease gene (heterozygotes) may exhibit some of the symptoms associated with the disorder. Approximately six affected families (kindreds) have been reported in the medical literature. Most symptoms of Juberg-Marsidi syndrome may be apparent at birth or soon thereafter.
Juberg-Marsidi syndrome may be diagnosed at birth or during early infancy, based upon a thorough clinical evaluation and characteristic physical findings. Craniofacial abnormalities, low birth weight, genital malformations, and/or hearing impairment may be apparent at birth. Hearing impairment or deafness may be confirmed through a variety of specialized hearing (auditory) tests. Abnormalities in motor coordination, speech, and intellect may be monitored during infancy and childhood.
The treatment of this 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, speech pathologists, nutritionists, specialists who assess and treat hearing problems (audiologists), eye specialists, and other health care professionals may need to systematically and comprehensively plan an affected child's treatment.
A variety of methods may be used to treat and correct eye abnormalities. Surgery, corrective glasses, or contact lenses may be used to help improve vision. In some cases, hearing aids may be used for those with hearing impairment.
Early intervention is important in ensuring that affected children with Juberg-Marsidi syndrome reach their potential. Special services that may be beneficial to affected children may include special remedial education and other medical, social, and/or vocational services.
Genetic counseling will be of benefit for affected individuals and their families. Other treatment for Juberg-Marsidi syndrome is symptomatic and supportive.
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:
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For information about clinical trials sponsored by private sources, contact:
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., mental retardation, short stature, hearing impairment, etc.].)
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Villard L, Toutain A, Lossi AM, et al. Splicing mutation in the ATR-X gene can lead to a dysmorphic mental retardation phenotype without alpha-thalassemia. Am J Hum Genet. 1996;58:499-505.
FROM THE INTERNET
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