Glossary in Congenital Malformations

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General:

#Malformation: a morphological defect, including absence, of an organ, or larger region of the body resulting from an intrinsically abnormal developmental process.

#Marcus-Gunn phenomenon (jaw-winking): this is a congenital phenomenon that is characterized by  elevating or drooping eyelids associated with jaw movement, smilling, swallowing, or speaking; can be acquired or congenital. It is thought to be due to misconnection between the third and fifth, and other cranial nerves. See also anormalous axonal connection (guidance) syndromes,

#Macrocephaly (megalocephaly): excessive occipitofrontal circumference without regard to cause or brain size.

#Membranis reuniens dorsalis of von Recklinghausen: During closure of the vertebral column, the dorsal part of the spinal cord is first composed of a mass of connective tissue and cartilage. The two lateral processes grow medially and eventually fuse. The membranis renuiens dorsalis of von Recklinghausen is the deepest part of this tissue mass that separates the spinal cord from the overlying connective tissue and epithelium.

#Meningocele: Herniation of the meninges through a defect in the cranium or vertebral column.

         Rudimentary meningocele: this includes atretic meningocele, heterotopic neural rest, ectopic glial tissue, congenital head tumor, epicranial arachnoidal cyst, primary cutaneous meningioma, and meningocele without central connection. They are not attached to cerebral structures. They are more commonly seen in the head than in the spine. Typically, they appear either as small skin-covered plaques or nodules without either hair or skin appendages and lack neuronal and glial elements. They may become cystic despit not connected to the spinal canal or the absence of choroid plexus.

#Meningomyelocele: Both meninges and spinal cord herniate thorugh a large vertebral defect. The spinal cord or nerve roots are frequently involved in the formation of the wall and the dorsal part of the spinal cord often remains open. Meningomyelocele above T12 have increased tendency to be associated with malformations in other systems whereas lower meningomyeloceles are not.

#Metopic: relating to the forehead or anterior portion of the cranium.

#Microencephaly: Abnormally small head.

#Microdysgenesis: Subtle structural abnormalities of cortical architecture.

#Microgyria: Microgyria is characterized by small gyri. The underlying cortex is normal and there is no fusion of molecular layer between two adjacent gyri.

#Micromelia: Abnormally small and short limbs.

#Multicystic encephalopathy: multiple cortical and subcortical cystic spaces secondary to necrosis. The spaces are lined by gliotic tissue. The surrounding tissue generally shows varying degrees of ischemic-hypoxic-type lesions associated with cytoarchitectonic abnormalities.

#Muscle-eye-brain syndromes: These syndromes are characterized by a variety of cerebral and/or cerebellar cortical malformation, abnormal cortical vascular architecture, and congenital muscular dystrophy. The eyes are frequently affected. They include, in decending order of severity, Fowler syndrome, Walker-Warburg syndrome, Fukuyama congenital muscular dystrophy, and muscle-eye-brain disease of Santavuori. In common, they have smaller than normal brain, abnormal cerebral cortical vessels and abnormalities in muscle. Neuronal migration disorders are not uncommon.

#Myelocystocele: a localized, cystic dilation of the central canal of the spinal cord that may be associated with dorsal or ventral meningoceles of the cervicothoracic or lumbroscral spine.

#Myelodysplasia: Myelodysplasia may be due to imperfect closure of the neural plate but it can also be present in a closed spinal cord. Histologically, there is a variety of anomalies in the area of the central canal and in the white and gray matters, although more or less complete closure of the neural plate had taken place. The more common clinical features include persistent enuresis, mild sensory disturbances in the lower portions of the body and inconspicuous reflex anomalies.

#Myeloschisis: cleft spinal cord resulting from failure of the neural folds to close normally in the formation of the neural tube, inevitably spina bifida is a sequel. The open neural plate ("open book" neuroplate) is not covered by skin, meninges, or vertebral arch.

 

Syndromes and SequencesHead

#Meckel-Gruber Syndrome (Meckel syndrome): Autosomal recessive and is lethal.  It seems that the mutant gene in Merkel-Gruber syndrome is variable. This condition is a neural tube defect. It consists of a variable cranial and CNS malformation with or without cranial rachischisis and occipital encephalocele, microcephaly, and eye anomalies with cystic dysplasia of the kidneys and malformation of other organs with the most consistent ones include hepatic fibrosis, hepatic "ductal plate malformation" and severe hypoplasia of the male genitalia associated with cryptochidism.

         Definition of Meckel-Gruber syndrome: "cystic kidney dysplasia plus at least two other defects which include relevant anomalies of brain (usually), heart, liver, genitalia, spleen, eye, urinary system or lip.

         CNS malformations: the most common "triad" includes prosencephalic dysgenesis, occipital encephalocele, and rhombic roof dysgenesis. Other neuronal migration defects are also common. The most consistent findings include:

         Prosencephalic dysgenesis, arhinencephaly-holoprosencephaly and other midline anomalies,

         Occipital encephalocele taking the form of extrusion of parts of the rhombic roof through the posterior fontanelle.

         Rhombic dysgenesis, notably supracerebellar cyst, vermal agenesis, stenosis of the aqueduct and flattening and dysplasia of the brain stem.

#Miller-Dieker Syndrome (17p syndrome):

         Summary: Miller-Dieker syndrome is a migration disorder characterized by lissencephaly.

         Genetics: Deletion or translocation of chromosome 17p13.3 is the salient feature, however, Miller-Dieker syndrome is a continuous gene syndrome and probably involves deletion of more than one gene. It typically comes with characteristic facial dysmorphism and other features. The critical gene is PAFAH1B1 (b-subunit of platelet activating factor acetylhydrolase, brain isoform Ib; formerly known as lissencephaly-1 or LIS1), located on a 350 kb critical region on chromosome 17p13.3. The most common genetic abnormality is complete deletion. The deletion is heterogenous, that means half the dosage of the gene product is not sufficient for normal development. This gene is related to Miller-DIeker syndrome and isolated lissencephaly syndrome. See also isoloated lissencephaly sequence.

         Clinical features: the infants are often severely spastic, with infantile spasm, and oblivious to their envrionement, and profound mental retardation. Usually die in the first two years of life. Characteristic facial dysmorphism with bitemporal hollowing and small jaw, short nose withupthurned nares, and a long and protuberant upper lip with thin vermillion border and relatively flattened midface. Other malformations may also be seen.

         Gross pathology: the spectrum varies from diffuse agyria to frontal pachygyria with parietooccipital agyria to diffuse pachygyria. Typically the posterior part of the brain, in contrast to X-linked lissencephaly, is more affected. Large ventricles, and sometimes, ventricular heteropia are also seen.

         Histology: the cerebral cortex show abnormal architecthre. They may have a molecular layer, then a broad band where cortical neurons show a marked radial arrangement, then deep to that a band of neurons randomly arranged. The inferior olivary nuclei are poorly convoluted, and heterotopic remnants of these nuclei lie in the migrator track of these nuclei from the rhombic lip whtere the young olivary neurons are generated. Cerebellum may show mild dysplasia, subcortical Purkinje cell heterotopias, and Purkinje cell lost.

#Mbius Syndrome: a congenital facial paralysis characterized by facial diplegia (facial paralysis) typically associated with bilateral abducens palsy (internal strabismus) and, occasionally, with involvement of several cranial nerves, especially the lower cranial pairs. Mbius syndrome has been used to describe a variety of heterogenous syndrome with features of 6th and 7th cranial nerve palsy. But according to Margret Norman's book, the term Mbius syndrome should only be used in patients with bilateral 6th and 7th cranial nerve palsy that is fully conscious, have no central respiratory depression, and in whom limb or muscle defects are absent or minimal. The etiology of Mbius syndrome is unknown. In most cases it probably is the result of a focal destructive lesion in the brain stem that may be resulted from hypoxic-ischemic, hemorrhagic or even thromboembolic. The combined presentation of 6th and 7th nerve palsy may be resulted from the close location of these two cranial nerve nuclei. Also, the 7th nerve wraps around the abducen nuclei.

#Multiple lethal pterygia syndrome: joints are fixed and skin webs form at the fixed joint. A pterygium can form at a single joint or at more than one joint and not be lethal. Pterygia form when the age of onset is between 9 to 12 weeks.

#Neu-Laxova Syndrome:

         Clinical: This is a migration disorder. A rare, lethal, probably autosomal recessive syndrome comprising severe intrauterine growth retardation, extreme microcephaly (the size of the brain is about 1/10 to 1/20 of normal), characteristic grotesque facies, flexion deformities of the limbs, short neck, scaly skin (sometimes described as ichthyosis or hyperkeratosis), edema of hands and feet, and hypoplasia of various organs. CNS

         Pathology: the brain is smooth or has mild grooving. Many structures are poorly developed or rudimentary, these include the hippocampus, olfactory and optic nerves, roof of the third and fourth ventricles, spinal cord, and cerebellum. The cortical neurons are small and closely packed and have failed to grow or mature and there is a paucity of primitive neuroectodermal cells in the subependymal regions. Corpus callosum is usually absent.

         Pathogenesis: may be resulted from excessive or premature cell death in the ventricular zone.

NeuroLearn NeuroHelp Malformations General Syndromes For Comment: KarMing-Fung@ouhsc.edu