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Copyright 2006, 2011
NORD is very grateful to Joseph Levy, MD, Professor of Pediatrics, Director, Division of Gastroenterology, NYU School of Medicine, for assistance in the preparation of this report.
Levy-Yeboa syndrome (LYS) is a recently recognized, inherited (congenital), multi-system disorder involving signs of musculoskeletal involvement such as low muscle tone and stiffening of the joints of the arms and legs (contractions), loss of hearing (neuronal deafness), intense burn-like eruptions of the skin containing clear fluid (bullous eruptions) and dangerous gastrointestinal distress involving substantial loss of fluids (secretory diarrhea), among other issues. Most, if not all, of these signs are apparent at, or within a few months of, birth.
Children with Levy-Yeboa syndrome appear to have blank expressions in their faces. This is due to the low tone of the muscles that normally reflect emotions..
As of June 2006, three children of one family have been reliably diagnosed with LYS. A child in another family died before a definitive diagnosis could be made.
In the one family, a decrease in fetal movement was noted five weeks before delivery. Clinicians consider the decrease in fetal movement to be the earliest expression of the failure of muscle strength and tone (myopathy) that is so much a part of the syndrome. Further signs of the myopathy include contractures of the arms and legs joints, so that the limbs appear rigidly bent (sharp angulation). The elbows, wrists, hips, and ankles are mainly involved. In addition, the impassive, mask-like, expressionless face is considered to be another sign of the myopathy.
Neurosensory deafness was confirmed in early infancy.
In LYS there are three primary symptoms involving the skin. These are:
1. Eruptions of fluid-filled blisters that resemble a skin disease known as epidermolysis bullosa simplex (EBS). These blisters were most obvious on the hands and feet, and cleared up in the first 3-6 months.
2. Generalized red (erythematous) rash, described as "fiery" and resembling first and second degree burns, occurs as a result of exposure to antibiotics and other drugs in the course of treatment.
3. Replacement of the red rash by intensely dark colored skin (hyperpigmentation) arising next to linear areas of low pigmentation (hypopigmentation) at the site of scars and punctures from hypodermic needles.
The loss of fluids with high sodium content that occurs as a result of secretory diarrhea may result in losses of more than one quart of fluid per day , even in the absence of any oral fluid intake. This is potentially lethal and probably the most dangerous clinical manifestation of LYS. This watery stool is easily overlooked since it may readily be mistaken for urine, delaying treatment with appropriate fluid replacement. Such diarrhea may present at any time from the first month to the sixth month of age, and tends to recur during intercurrent infections. The profuse diarrhea is believed to be responsible for the loss of important micronutrients, such as zinc, which in turn might play a role in the skin disorder. Indeed, skin biopsies suggested nutritional deficiencies and the skin condition improved with zinc replacement.
The cause of Levy-Yeboa syndrome remains unknown. Early in the investigation of LYS, it was thought that the disorder might be the result of defect(s) in the cell's factories for the synthesis and breakdown of energy-producing molecules, the mitochondria. The clinical researchers most familiar with the syndrome rule out mitochondrial defects as the source of the disorder as a result of muscle biopsies of tissue from brother, sisters, and metabolic blood screening of parents.
These same clinicians suspected that the cause may be related to defects in the gene that controls the passages in the cell wall membrane through which potassium ions flow, the gene known as KCNQ. Defects in this gene could help to explain the gastrointestinal symptoms as well as the neurosensory deafness since such symptoms in other syndromes have been definitely linked to alterations in this gene. In addition, it is well known that mutations in the KCNQ1 and KCNE genes generate substantially different symptoms and signs in different people (pleiotropic effects). However, the relation of LYS to the KCNQ1 and KCNE3 genes was recently ruled out by linkage studies.
Therefore, any of these conjectures remains "not proven" at this time.
There are too few instances or definitive cases of LYS to make any decisions regarding the incidence or prevalence of the disorder, or whether there are any biases regarding the sex of the child or ethnicity.
As this syndrome becomes better and more widely known, more cases of LYS may be reported in the literature.
Arthrogryposis multiplex congenita
Arthrogryposis multiplex congenita, a rare disorder that is present at birth (congenital), is characterized by reduced mobility of many joints of the body. Impairment of mobility is due to the overgrowth (proliferation) of fibrous tissue in the joints (fibrous ankylosis). There are many different types of arthrogryposis multiplex congenita and the symptoms vary widely among affected individuals. In the most common form, the range of motion of the joints in the arms and legs (limbs) is limited or fixed. Other findings may include inward rotation of the shoulders, abnormal extension of the elbows, and bending of the wrists and fingers. In addition, the hips may be dislocated and the heels of the feet may be inwardly bent from the midline of the leg while the feet are inwardly bent at the ankle (clubfoot). The cause of arthrogryposis multiplex congenita (AMC) is unknown. Most types are not inherited; however, a rare autosomal recessive form of the disease has been reported in one large inbred Arabic kindred in Israel.
Epidermolysis bullosa simplex
Epidermolysis bullosa (EB) refers to a group of rare, inherited skin diseases characterized by recurring painful blisters and open sores, often in response to minor trauma, as a result of the unusually fragile nature of the skin. Some severe forms may involve the eyes, tongue, and esophagus, and some may produce scarring and disabling musculoskeletal deformities. There are three major forms: epidermolysis bullosa simplex (EB simplex), the most common; dystrophic epidermolysis bullosa (DEB), and junctional epidermolysis bullosa (JEB).
The diagnosis is based on the clinical picture presented in the child's first few weeks or months. A late decrease in fetal movement may be sufficient to raise suspicions or concerns regarding Levy-Yeboa syndrome. The combination of major symptoms, myopathy, deafness, skin eruptions and recurrent, massive, watery stools is definitive.
The management of infants and children with LYS is demanding since so many different organ systems are affected and the patients are so young.
Over time, intensive physical therapy may correct the deformities of the limbs. Also, there may be some improvement in the bland, blank facial expressions of the affected individual as he or she grows older.
The burn-like skin symptoms require considerable attention at the site and systemically. Creams and other topical treatments used for the management of burns may ease the discomfort and minimize the chances of infection.
The secretory (watery) diarrhea should be treated intermittently with intravenous nutrition for the first year of life. The bouts of diarrhea may ease after variable periods of time. In the opinion of the clinicians managing the cases diagnosed to date, the diarrhea appeared in some instances to be associated with infections that may or may not affect the digestive tract directly. Treatment with zinc supplements (oral 20mg/day zinc chloride for maintenance; intravenous 400-600 mcg/kg/day zinc as zinc sulphate during periods of worsening of the diarrhea) appeared to be effective.
Hearing aids were of considerable help to the patients.
The intellectual and verbal skills of those affected have appeared to be normal, and their musculoskeletal handicaps have improved over the years as a result of intensive physical, educational and speech therapy. The three children with this diagnosis attend regular school where they are active and social as they are at home. After age 2 years their rate of hospitalization has decreased significantly. Episodes of high fever that require intravenous (IV) management and close monitoring are the main reasons for in-patient hospitalization at this time. After age 4 years, several episodes of diarrhea were ended and managed with administration of Pedialyte, (a rehydration fluid) via a gastric tube or, if tolerated, by mouth. Neither immunodeficiency nor opportunistic infections have been observed.
LYS is too new a syndrome to have generated clinical trials; however, when such are begun, they will be posted on the Internet as described below.
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:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
Contact for additional information about Levy-Yeboa syndrome:
Joseph Levy, MD
Professor of Pediatrics
Director, Division of Gastroenterology
NYU School of Medicine
PO Box 8126
Gaithersburg, MD 20898-8126
Phone #: 301-251-4925
800 #: 888-205-2311
Home page: http://rarediseases.info.nih.gov/GARD/
Levy J, Chung W, Garzon M, Gallagher MP, Oberfield SE, Lieber E, Anyane-Yeboa K. Congenital myopathy, recurrent secretory diarrhea, bullous eruption of skin, microcephaly, and deafness: a new genetic syndrome? Am J Med Genet A. 2003;116:20-25.
Report last updated: 2011/03/01 00:00:00 GMT+0