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Last updated:
March 20, 2014
Years published: 2006, 2011, 2014
NORD gratefully acknowledges Joseph Levy, MD, Director, Special Projects, Division of Gastroenterology, Professor of Pediatrics, 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 March 2014, three children of one family have been reliably diagnosed with LYS. A child in another family died before a definitive diagnosis could be made.
MYOPATHY
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
Neurosensory deafness was confirmed in early infancy.
DERMATOLOGY
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.
SECRETORY DIARRHEA
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.
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.
Treatment
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. The intensity and frequency of the secretory diarrhea episodes tends to get better over time. However, when it reappears, management is challenging as stool volume losses are remarkable.
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
Email: prpl@cc.nih.gov
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
Contact for additional information about Levy-Yeboa syndrome:
Joseph Levy, MD
Director, Special Projects
Division of Gastroenterology
Professor of Pediatrics
NYU School of Medicine
212-263-5407
JOURNAL ARTICLES
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.
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NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
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