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MAJOR CATEGORIES OF NEUROLOGIC DISEASE
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surface, leading to a nodularity of the surface described as a cobblestone appearance In the three disorders with this pathologic nding, the clinical picture is one of mental retardation conjoined with congenital muscular dystrophy Three identi ed gene defects are thought to alter the glycosylation of critical proteins in the brain and in skeletal muscle These genes include the gene fukutin in Fukuyama muscular dystrophy (page 1224), the POMGNT1 gene in muscle-eye-brain disease, and the POMT1 gene in Walker-Warburg syndrome (page 1224) as summarized in Table 38-3
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Combined Cerebral, Cranial, and Somatic Abnormalities
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As has been remarked, many diseases that interfere with cerebral development also deform the cranial and facial bones, eyes, nose, and ears Such somatic stigmata therefore assume signi cance as indicators of altered cerebral structure and function Moreover, they constitute irrefutable evidence that the associated neural abnormality is in the nature of a maldevelopment, either hereditary or the result of a disease acquired during the intrauterine period There are so many cerebrosomatic anomalies that one can hardly retain visual images of them, much less recall all the physicians names by which they are known Of necessity one turns to atlases, one of the best of which has been compiled by Holmes and colleagues and is based on clinical material drawn in large part from the Fernald School and Eunice K Shriver Center in Massachusetts The reader may also turn to the books by Gorlin and colleagues and by Jones for speci c information Ford s Diseases of the Nervous System in Infancy, Childhood, and Adolescence is still a valuable reference, as is Jablonski s Dictionary of Syndromes and Eponymic Diseases There is some advantage in grouping these anomalies according to whether the extremities, face, eyes, ears, and skin are associated with a cerebral defect The sheer number and variety of these anomalies permit only an enumeration of the more common ones and their most obvious physical characteristics To identify a particular anomaly, one must turn to the specialized monographs and atlases mentioned above Unfortunately, apart from certain genetic linkages, no useful leads as to their origin have been forthcoming The Syndactylic-Craniocerebral Anomalies (Acrocephalosyndactyly) Commonly, fusion of two ngers or two toes or the presence of a tab of skin representing an extra digit may be seen at birth in an otherwise normal individual However, as pointed out above, when syndactylism is of more severe degree and is accompanied by premature closure of cranial sutures, the nervous system usually proves to be abnormal as well The general term acrocephalosyndactyly is used to describe the several combinations of craniostenotic and facial deformities and fusion of digits Several of these disorders are a consequence of mutations in genes encoding one of two broblast growth factors or proteins related to them The following descriptions include only the major features; most have, in addition, distinctive malformations of the orbits, ears, and palate 1 Acrocephalosyndactyly types I and II (typical and atypical Apert syndrome) Turri-brachycephalic skull, syndactyly of hands and feet ( mitten hands, sock feet ), moderate to severe mental retardation Acrocephalosyndactyly III (Saethre-Chotzen syndrome) Various types of craniostenosis, proximally fused and shortened
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digits, moderate degree of mental retardation Transmission as an autosomal dominant trait Acrocephalosyndactyly IV (Pfeiffer syndrome) Turri-brachycephaly; broad, enlarged thumbs and great toes; partially exed elbows (radiohumeral or radioulnar synostoses); mild and variable mental retardation; autosomal dominant inheritance Acrocephalopolysyndactyly V (Carpenter syndrome) Premature fusion of all cranial sutures with acrocephaly, at bridge of nose, medial canthi displaced laterally, excess digits and syndactyly, subnormal intelligence Acrocephalosyndactyly with absent digits High, bitemporally attened head; absent toes and syndactylic ngers; moderate mental retardation Acrocephaly with cleft lip and palate, radial aplasia, and absent digits Microbrachycephaly due to craniostenosis, cleft lip and palate, absent radial bones, severe mental retardation Dyschondroplasia, facial anomalies, and polysyndactyly Keel-shaped skull and ridge through center of forehead (metopic suture), short arms and legs, postaxial polydactyly and short digits, moderate mental retardation
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In all the foregoing types of syndactylism and cranial abnormality, which may be regarded as variants of a common syndrome, the diagnosis can be made at a glance because of the deformed head, protuberant eyes, and abnormal hands and feet The degree of mental retardation proves to be variable, usually moderate to severe, but occasionally intelligence is normal or nearly so The brain has been examined in only a few instances and not in a fashion to display fully the type and extent of this developmental abnormality Other Craniocephalic-Skeletal Anomalies Members of this group have distinctive anomalies of the cranium, face, and other parts, but craniostenosis is not a consistent feature Craniofacial dysostosis (Crouzon syndrome) Variable degrees of craniosynostosis; broad forehead with prominence in the region of the anterior fontanel region; shallow orbits with proptosis; midline facial hypoplasia and short upper lip; malformed auditory canals and ears; high, narrow palate; moderate mental retardation As noted above, a genetic defect in one of the broblast growth factor receptors is responsible for about one-third of cases that are not associated with other deformities (Moloney et al) Autosomal dominant inheritance is seen in most cases 2 Median cleft facial syndrome (frontonasal dysplasia; hypertelorism of Greig) Widely spaced eyes, broad nasal root, cleft nose and premaxilla, V-shaped frontal hairline, heterotypic anterior frontal fontanel (midline cranial defect); mild to severe mental retardation 3 Chondrodystrophia calci cans congenita (chondrodysplasia punctata, Conradi-Hunermann syndrome) Prominent fore head; at nose; widely separated eyes; short neck and trunk with kyphoscoliosis; dry, scaly, atrophic skin; cicatricial alopecia; irregularly deformed vertebral bodies; mental retardation infrequent Severe shortening of limbs in some cases 4 Orofaciodigital syndrome All the patients are female Pseudoclefts involving the mandible, tongue, maxilla, and palate; 1
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