Neu Laxova Syndrome
Neu Laxova Syndrome
National Organization for Rare Disorders, Inc.
It is possible that the main title of the report Neu Laxova Syndrome is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.
Related Disorders List
Information on the following diseases can be found in the Related Disorders section of this report:
Neu-Laxova syndrome (NLS) is a rare genetic disorder that is inherited as an autosomal recessive trait. The syndrome is characterized by severe growth delays before birth (intrauterine growth retardation); low birth weight and length; and distinctive abnormalities of the head and facial (craniofacial) region. These may include marked smallness of the head (microcephaly), sloping of the forehead, widely spaced eyes (ocular hypertelorism), and other malformations, resulting in a distinctive facial appearance. NLS is also typically characterized by abnormal accumulations of fluid in tissues throughout the body (generalized edema); permanent flexion and immobilization of multiple joints (flexion contractures); other limb malformations; and/or abnormalities of the brain, skin, genitals, kidneys, and/or heart.
NLS is associated with distinctive abnormalities before birth. These may include severely delayed growth (intrauterine growth retardation); excessive fluid in the thin-walled membrane (amniotic sac) surrounding the fetus during pregnancy (polyhydramnios); abnormally reduced fetal movements; a short umbilical cord; and an abnormally small placenta. (The placenta is the organ within the uterus that joins the blood supplies of the mother and the developing fetus.) In addition, in some cases, the umbilical cord may have only two blood vessels. (The umbilical cord, which is the flexible structure that connects the fetus with the placenta, normally has two umbilical arteries as well as a larger umbilical vein.)
Newborns with NLS typically have an abnormally low birth weight and length as well as marked smallness of the head (microcephaly). Additional malformations of the head and facial (craniofacial) area are also usually present, resulting in a characteristic appearance. Such abnormalities include a sloping forehead; a flattened nose with a broad nasal bridge; full cheeks; and a small, underdeveloped jaw (micrognathia). Affected newborns may also have large, low-set, malformed (dysplastic) ears; a round, gaping mouth with thick lips; a short neck; and widely set, unusually prominent eyes. In addition, the eyelids are underdeveloped (hypoplastic) and turned outward (ectropion), causing them to appear absent. Additional eye (ocular) abnormalities may also be present, such as unusually small eyes (microphthalmia) and loss of transparency of the lenses of the eyes (cataracts). Some affected newborns may also have incomplete closure of the roof of the mouth (cleft palate) and a vertical groove in the upper lip (cleft lip).
NLS is also associated with musculoskeletal abnormalities, including permanent flexion and immobilization of major joints (flexion contractures), such as the elbows, wrists, hips, knees, and ankles, with skin webbing across certain immobilized joints (e.g., elbows and knees). In addition, the arms and legs are unusually short, and the hands and feet may be swollen. Affected newborns may also have overlapping fingers; webbed or fused fingers and toes (syndactyly); and a deformity in which the feet appear shaped like the rocker of a rocking chair (rocker-bottom feet). In addition, there may be "underossification" of bones in the hands and feet and other abnormalities of bone formation. (Ossification refers to the conversion of fibrous tissue or cartilage into bone.)
The disorder is also typically characterized by an abnormal accumulation of fluid in tissues throughout the body (generalized edema). In addition, some infants may have abnormal (i.e., myxomatous) proliferation of connective tissue or excessive fatty deposits beneath the outermost layer of skin (epidermis), with degeneration (atrophy) of surrounding muscles. Less commonly, edema may not be present or may be restricted to the scalp. Some affected infants may also have yellowish, dry, scaling ("ichthyotic") skin.
NLS may also be associated with malformations of the brain. In many cases, there is incomplete development of the folds (gyri) of the outer region of the brain (cerebral cortex), causing the brain's surface to appear unusually smooth (agyria). Additional malformations may include absence of the thick band of nerve fibers that connects the two hemispheres of the brain (agenesis of the corpus callosum) or underdevelopment (hypoplasia) of the cerebellum, which is the region of the brain that plays an essential role in coordinating voluntary movements and maintaining proper posture. In addition, in some instances, there may be cystic malformation of the fourth cavity (ventricle) of the brain (Dandy-Walker malformation) and associated hydrocephalus. Hydrocephalus is a condition in which there is impaired flow or absorption of the fluid that circulates through the ventricles of the brain and the spinal canal [cerebrospinal fluid (CSF)], potentially leading to increasing fluid pressure in the brain, a rapid increase in head size, or other associated findings. In some cases, NLS may also be associated with additional abnormalities of the brain and spinal cord (central nervous system).
Some affected newborns may also have additional physical abnormalities, such as underdevelopment of the genitals; absence of one of the kidneys (unilateral renal agenesis) or other renal defects; underdevelopment of the lungs (pulmonary hypoplasia); or structural abnormalities of the heart (congenital heart defects). Congenital cardiac malformations may include an abnormal opening in the fibrous partition (septum) that separates the upper or lower chambers of the heart (atrial or ventricular septal defects); persistence of the fetal opening between the two major arteries (aorta, pulmonary artery) emerging from the heart (patent ductus arteriosus); or a heart defect in which the aortic and pulmonary arteries are in one another's normal positions (transposition of the great arteries). Infants with NLS may be stillborn or develop life-threatening complications shortly after birth.
NLS is transmitted as an autosomal recessive trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, 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 for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.
The parents of several individuals with NLS have been closely related by blood (consanguineous). In recessive disorders, if both parents carry the same gene for the same disease trait, there is an increased risk that their children may inherit the two genes necessary for development of the disease.
A few cases have also been reported in which NLS has appeared to occur randomly for unknown reasons (sporadically).
There has been one reported case of NLS that has occurred for no apparent reason (sporadically). Several cases of this disorder have been associated with "blood" related parents.
NLS appears to affect males and females in relatively equal numbers. Since the disorder was originally described in three siblings in 1971 (Neu, RL) as well as three siblings in another family in 1972 (Laxova, R), over 30 additional cases have been reported. Investigators suggest that the disorder may have a higher frequency in Pakistanis than in other geographic or ethnic populations.
Symptoms of the following disorders may be similar to those of NLS. Comparisons may be useful for a differential diagnosis:
Cerebro-oculo-facio-skeletal (COFS) syndrome is a rare genetic disorder that is sometimes referred to as Pena-Shokeir syndrome type II. Some researchers suggest that NLS and COFS syndrome may represent the same disease entity. (Other investigators have indicated that COFS syndrome and another condition known as Bowen Hutterite syndrome may be the same disorder. [For information on Bowen Hutterite syndrome, please see the description below.]) COFS syndrome is characterized by severe, progressive growth delays after birth (postnatal growth deficiency); characteristic craniofacial malformations, resulting in a distinctive facial appearance; eye (ocular) abnormalities; musculoskeletal defects; and malformations and progressive degenerative changes of the brain and spinal cord (central nervous system). Infants with COFS syndrome fail to gain weight as expected and experience little growth despite an apparently sufficient intake of calories (failure to thrive). Distinctive craniofacial malformations include an unusually small head (microcephaly); a prominent nose and high nasal bridge; an overhanging upper lip; a small mouth, underdeveloped jaw (micrognathia), and receding chin; and large, low-set ears. Most affected infants also have narrow eyelid folds (palpebral fissures), unusually small eyes (microphthalmia), loss of transparency of the lenses of the eyes (cataracts), and/or other ocular abnormalities. Characteristic musculoskeletal defects include permanent flexion of certain fingers (camptodactyly) and particular joints of the arms and legs (flexion contractures); abnormal front-to-back and/or sideways curvature of the spine (kyphosis and/or scoliosis); rocker-bottom feet; characteristic defects of the hips and pelvis; and/or other abnormalities. In addition, central nervous system (CNS) abnormalities are usually present including severe intellectual disability; certain malformations of the brain (e.g., cerebellar hypoplasia, hypoplasia or agenesis of the corpus callosum); and progressive degeneration of myelin (demyelination), a fatty, protective substance around certain nerve fibers that enables the effective transmission of nerve signals. Infants and children with the disorder are also prone to repeated respiratory infections and may experience increasing difficulties breathing (respiratory distress). COFS syndrome is thought to be inherited as an autosomal recessive trait. (For further information, choose "Cerebro-oculo-facio-skeletal" or "COFS" as your search term in the Rare Disease Database.)
Bowen Hutterite syndrome is a rare genetic disorder that has primarily occurred in individuals of Hutterite descent. The disorder is characterized by growth delays before birth (intrauterine growth retardation); failure to grow and gain weight at the expected rate (failure to thrive) during infancy; distinctive craniofacial abnormalities, such as an abnormally small head (microcephaly), a prominent nose, and a small, underdeveloped jaw (micrognathia); and other physical abnormalities. These may include restricted joint movements, abnormal deviation (clinodactyly) or permanent flexion (camptodactyly) of the fifth fingers, rocker-bottom feet, and/or undescended testes (cryptorchidism) in affected males. Some affected infants may also have kidney (renal), brain, and/or other malformations. Bowen Hutterite syndrome is inherited as an autosomal recessive trait. (For more information on this disorder, choose "Bowen Hutterite" as your search term in the Rare Disease Database.)
Fetal akinesia sequence, also known as Pena-Shokeir syndrome type I, is characterized by growth deficiency before birth (intrauterine growth retardation); severely underdeveloped lungs (pulmonary hypoplasia) and difficulties breathing (respiratory distress) at birth; permanent flexion and immobilization of several joints; and characteristic craniofacial malformations. Many researchers suggest that fetal akinesia sequence does not represent a particular syndrome or distinct disease entity, but rather the occurrence of characteristic symptoms and physical findings (typical phenotype) due to abnormally decreased movement during fetal development (fetal hypokinesia or akinesia) and muscle weakness from many different underlying causes. Infants with fetal akinesia sequence typically have moderate joint contractures of the wrists, elbows, hips, knees, and ankles; skin webbing across certain immobilized joints; permanent flexion (camptodactyly) and abnormal deviation of certain fingers toward the "pinky" side of the hand (ulnar deviation); malformations of the feet (e.g., clubfeet [talipes equinovarus] or rocker-bottom feet); and/or other musculoskeletal abnormalities. Characteristic craniofacial malformations may include a high nasal bridge with a depressed nasal tip; widely spaced eyes (ocular hypertelorism); low-set, malformed ears; an abnormally small, retracted jaw (microretrognathia); and/or incomplete closure of the roof of the mouth (cleft palate). Affected infants may also have additional abnormalities including an unusually short and/or webbed neck, malformations of the genital and urinary (genitourinary) tracts, heart defects, and/or other malformations. Researchers suggest that fetal akinesia sequence may result from many different underlying neurological (neurogenic) or muscular (myopathic) disorders and/or other factors. (For further information on this disorder, choose "fetal akinesia" or "Pena Shokeir" as your search term in the Rare Disease Database.)
Restrictive dermopathy is a rare genetic disorder that is inherited as an autosomal recessive trait. The disorder is associated with severe growth delays before birth; excessive fluid in the thin-walled membrane (amniotic sac) surrounding the fetus (polyhydramnios); a short umbilical cord; and abnormally reduced movements during fetal development. In addition, affected newborns typically have rigid, tense, adherent skin; underdeveloped lungs (pulmonary hypoplasia); permanently flexed, immobilized joints (contractures); rocker-bottom feet; and other skeletal abnormalities. Newborns also have characteristic craniofacial malformations, such as widely spaced eyes (ocular hypertelorism); outwardly turned eyelids (ectropion); a small, pinched nose; a small, open mouth; and an underdeveloped jaw (micrognathia). Affected infants may be stillborn or develop life-threatening complications shortly after birth.
Multiple pterygium syndrome is a rare genetic disorder characterized by abnormal growth delays (growth retardation), webbing of the skin (pterygium) in several areas of the body, permanent flexion of certain joints (contractures), skeletal abnormalities, and craniofacial malformations. Affected individuals typically have webbing of the neck (pterygium colli), of the fingers (syndactyly), under the arms (axillae), in the crook of the elbows (antecubital fossae), and behind the knees (popliteal fossae); multiple joint contractures; permanent flexion of certain fingers and toes (camptodactyly); and foot deformities, such as rocker-bottom feet. Individuals with the disorder may also have abnormal front-to-back and sideways curvature of the spine (kyphoscoliosis) and other malformations of bones of the spinal column (vertebrae); abnormalities of the ribs; dislocation of the hips; and/or other skeletal malformations. Craniofacial defects may include an abnormally small jaw (micrognathia), drooping of the upper eyelids (ptosis), downwardly slanting eyelid folds (palpebral fissures), vertical skin folds that may cover the eyes' inner corners (epicanthal folds), and low-set ears. In addition, genital and/or other abnormalities may be present. In most cases, the disorder appears to occur randomly for unknown reasons (sporadically). (For more information on this disorder, choose "multiple pterygium" as your search term in the Rare Disease Database.)
There are also several rare autosomal recessive forms of multiple pterygium syndrome that may be characterized by decreased fetal movements (fetal hypokinesia or akinesia), multiple joint contractures, and skin webbing across joints. Additional features may include permanent flexion of certain fingers (camptodactyly); abnormal cystic growths consisting of widened (dilated) lymph vessels beneath the skin in the neck area (cystic hygroma); and/or abnormal accumulation of fluid in tissues throughout the body and in body cavities (fetal hydrops), such as around the lungs (pleural effusion), around the heart (pericardial effusion), and/or in the abdominal cavity (ascites). Affected individuals may also have an underdeveloped jaw (micrognathia), an unusually flat nose, an abnormal groove in the upper lip (cleft lip), incomplete closure of the roof of the mouth (cleft palate), and/or other craniofacial malformations; abnormally crowded, thin ribs; and underdevelopment (hyoplasia) of the heart and lungs. Life-threatening complications may occur during fetal development.
Trisomy 18 syndrome is a rare chromosomal disorder in which all or a critical region of chromosome 18 appears three times (trisomy) rather than twice in some (mosaicism) or all cells of the body. Depending on the specific location of the duplicated (trisomic) portion of chromosome 18--as well as the percentage of cells containing the abnormality--symptoms and findings may be extremely variable from case to case. However, before birth, abnormalities often include weak fetal activity, a small placenta, and excessive fluid in the membranous sac surrounding the developing fetus (polyhydramnios). After birth, characteristic findings include growth deficiency, feeding and breathing difficulties, developmental delays, intellectual disability, and, in affected males, undescended testes (cryptorchidism). Individuals with Trisomy 18 syndrome may also have distinctive craniofacial malformations, such as a small head (microcephaly) that appears unusually long and narrow (dolichocephaly); a prominent back region of the head (occiput); a small mouth (microstomia) and an underdeveloped jaw (micrognathia); incomplete closure of the roof of the mouth (cleft palate); an abnormal groove in the upper lip (cleft lip); and/or an upturned nose. Affected infants may also have narrow eyelid folds (palpebral fissures), widely spaced eyes (ocular hypertelorism), and drooping of the upper eyelids (ptosis). Malformations of the hands and feet are also often present, including overlapped, flexed fingers; webbing of certain toes (syndactyly); and a deformity in which the heels are turned inward and the soles are flexed (clubfeet [talipes equinovarus]). Infants with Trisomy 18 syndrome may also have a small pelvis with limited movements of the hips, a short breastbone (sternum), kidney malformations, and structural heart defects that are present at birth. Such cardiac defects may include an abnormal opening in the partition dividing the lower chambers of the heart (ventricular septal defect) or persistence of the fetal opening between the two major arteries (aorta, pulmonary artery) emerging from the heart (patent ductus arteriosus). (For further information on this disorder, choose "trisomy 18" as your search term in the Rare Disease Database.)
There are a number of other disorders that may be characterized by abnormally decreased movement during fetal development; growth delays; multiple joint contractures; skin webbing; craniofacial, central nervous system, cardiac, or renal malformations; and/or other abnormalities similar to those potentially associated with NLS. (For more information on such disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
A diagnosis of NLS may be suggested before birth (prenatally) based upon specialized testing, such as repeated fetal ultrasonography. During fetal ultrasonography, sound waves are used to create an image of the developing fetus. Such testing may reveal characteristic findings that suggest NLS, such as weak fetal activity, restricted limb movement, excessive fluid in the membranous sac surrounding the developing fetus (polyhydramnios), a small placenta, and intrauterine growth retardation. Additional findings seen on ultrasound that may suggest NLS include an abnormally small head, receding forehead, prominent eyes, joint contractures, and/or generalized edema.
The diagnosis of NLS may also be made or confirmed after birth (postnatally) based upon a thorough clinical evaluation and characteristic physical findings. Specialized testing may also be conducted to detect certain conditions that may potentially be associated with the disorder (e.g., congenital heart defects).
The treatment of NLS is directed toward the specific symptoms that are apparent in each individual. Such treatment may require the coordinated efforts of a team of medical professionals, such as pediatricians; physicians who diagnose and treat neurological disorders (neurologists); physicians who diagnose and treat heart abnormalities (cardiologists); and/or other health care professionals.
Specific therapies for the treatment of NLS are symptomatic and supportive. In addition, genetic counseling will be of benefit for affected families.
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