$Unique_ID{BRK03942} $Pretitle{} $Title{Lissencephaly} $Subject{Lissencephaly Lissencephaly Syndrome Agyria Miller-Dieker Syndrome Norman-Roberts Syndrome HARD plus/minus-E Syndrome Neu-Laxova Syndrome } $Volume{} $Log{} Copyright (C) 1987, 1990 National Organization for Rare Disorders, Inc. 454: Lissencephaly ** IMPORTANT ** It is possible the main title of the article (Lissencephaly) is not the name you expected. Please check the SYNONYMS listing on the next page to find alternate names, disorder subdivisions, and related disorders covered by this article. Synonyms Lissencephaly Syndrome Agyria DISORDER SUBDIVISIONS Miller-Dieker Syndrome Norman-Roberts Syndrome Information on the following diseases can be found in the Related Disorders section of this report: HARD plus/minus-E Syndrome Neu-Laxova Syndrome General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Lissencephaly is a brain formation disorder characterized by the lack of normal convolutions or folds in the brain. It is thought to be inherited. Two major subdivisions including Miller-Dieker Syndrome and Norman-Roberts Syndrome have been identified, although as many as eight variants of Lissencephaly may exist. An abnormally small head and an unusual facial appearance, as well as abnormalities of the brain, kidney, heart and gastrointestinal tract may occur. This disorder may occur alone or as a symptom of other medical conditions. Symptoms Lissencephaly means "smooth brain". It is characterized by an abnormally small head, an unusual facial appearance, difficulty in swallowing, failure to thrive, and severe psychomotor retardation. Abnormalities of the hands, fingers or toes, muscle spasms, and seizures may also occur. Patients with the Miller-Dieker variant of Lissencephaly tend to have a high, narrow forehead, prominent back of the head, clouded corneas of the eyes, minor abnormalities of the ears, underdeveloped jaw, lips with a "carp mouth" appearance, and the skin of the forehead may be abnormally wrinkled. A low, sloping forehead and prominent bridge of the nose are often present in those with the Norman-Roberts variant of Lissencephaly. No chromosomal abnormality exists in the Norman-Roberts form of Lissencephaly. Excessive hair growth (hirsutism) may cover many areas of the body. Symptoms in males may include undescended testicles and hernias. Other developmental problems such as congenital heart disease, absence of one kidney, and closure of the normal opening in the part of the intestine called the duodenum (duodenal atresia) may also occur. Infants with Lissencephaly may have a bluish coloration of the skin (cyanosis), a feeble cry, and breathing difficulties while sleeping. Diminished muscle tone (floppiness) and feeding problems may develop. Initial lack of movement may gradually be replaced by seizures, rigidity, and spasms marked by an extreme backward bend of the entire body. Patients may not respond to stimuli, but may be severely hyperactive at times. Some infants may have enlarged livers and spleens, prolonged yellow discoloration of the skin (jaundice), and urinary tract infections. Causes Lissencephaly is thought to be inherited as an autosomal recessive trait. (Human traits including the classic genetic diseases, are the product of the interaction of two genes for that condition, one received from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits the same defective gene from each parent. If one receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will show no symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is twenty-five percent. Fifty percent of their children will be carriers, but healthy as described above. Twenty-five percent of their children will receive both normal genes, one from each parent and will be genetically normal.) Medical researchers have found specific chromosomal abnormalities in some Lissencephaly patients and speculate that this may be the cause of Miller- Dieker Syndrome. Symptoms may develop due to interruption of normal fetal brain development during the fourth month of pregnancy. Affected Population Lissencephaly is a very rare disorder beginning before birth which is thought to affect males and females in equal numbers. Related Disorders The following disorders can include Lissencephaly as a symptom. Comparisons may be useful for a differential diagnosis: HARD plus/minus-E Syndrome is an acronym for a combination of Hydrocephalus, Agyria (smooth brain), and Retinal Dysplasia. This disorder is also known as HARD Syndrome, Warburg Syndrome, Chemke Syndrome, Pagon Syndrome, Walker-Warburg Syndrome, Cerebroocular Dysgenesis, or COD. The "E" in the name is included when an abnormal opening of the skull termed "encephalocele" occurs. Neu-Laxova Syndrome is marked by intrauterine growth deficiencies and multiple defects present at birth. Abnormalities of the membrane tissue connection between the wall of the uterus and the fetus (placenta) occur. Additionally, the fetus is born with a small head, lack of normal convolutions and folds of the brain (Lissencephaly or "smooth brain"), and developmental abnormalities of the limbs, skin, and external genitalia. Therapies: Standard Treatment of Lissencephaly is symptomatic and supportive. Genetic counseling will be of benefit to patients and their families. Therapies: Investigational This disease entry is based upon medical information available through March 1990. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Lissencephaly, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Lissencephaly Network 7121 Baer Rd. Ft. Wayne, IN 46809 (219) 747-1075 Dr. William B. Dobyns Indiana University School of Medicine Riley Hospital for Children Neurology Dept., Rm. N102 702 Barnhill Dr. Indianapolis, IN 46202 (317) 274-8747 Lissencephaly Network 7121 Baer Rd. Ft. Wayne, IN 46809 (219) 747-1075 NIH/National Institute of Neurological Disorders & Stroke (NINDS) 9000 Rockville Pike Bethesda, MD 20892 (301) 496-5751 (800) 352-9424 The Children's Brain Diseases Foundation for Research 350 Parnassus, Suite 900 San Francisco, CA 94117 (415) 566-5402 (415) 565-6259 For information on genetics and genetic counseling referrals, please contact: March of Dimes Birth Defects Foundation 1275 Mamaroneck Avenue White Plains, NY 10605 (914) 428-7100 Alliance of Genetic Support Groups 35 Wisconsin Circle, Suite 440 Chevy Chase, MD 20815 (800) 336-GENE (301) 652-5553 References MILLER-DIEKER SYNDROME: LISSENCEPHALY AND MONOSOMY 17P: W.B. Dobyns, et al.; J Pediatr (April 1983, issue 102(4)). Pp. 552-558. LISSENCEPHALY AND PACHYGYRIA: AN ARCHITECTONIC AND TOPOGRAPHICAL ANALYSIS: R.M. Stewart, et al.; Acta Neuropathol (Berl) (1975, issue 31(1)). Pp. 1-12. SYNDROMES WITH LISSENCEPHALY. I: MILLER-DIEKER AND NORMAN ROBERTS SYNDROMES AND ISOLATED LISSENCEPHALY: W.B. Dobyns, et al.; Am J Med Genet (July 1984, issue 18(3)). Pp. 509-526.