0025 Principal chondrodysplasias Not Detectable at Birth As in the case of those principal cliondrodys)Iasias detectable at birth, there are

five main areas .or study once it has been determined by the trian;ulation reasoning process that the disorder is either iereditary and/or congenital. These five main areas ire the following:
1. 2. 3. 4. 5.

The cranial area, which includes the calvaria, he face, and mental retardation The extremities The spine The pelvis The thoracic cage (which may include the )resence or absence of congenital heart disease)

To some extent there is some repetition of the :hondrodysplasias detectable at birth, since some of hese latter may not be manifest until after the age A 1 or 2 years and thus fall into both categories. In hose instances in which this occurs, the student will )e referred back to the ori ginal description under he chondrodysplasias detectable at birth. FIVE AREAS INVOLVED The extremities, thorax, vertebrae, pelvis, and lead are all involved to a greater or lesser extent in he following disorders:
1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16.

Marfan's syndrome (Fig. 4-16) Homocystinuria Osteogenesis imperfecta (Fig. 4-17) Achondroplasia Ehlers-Danlos syndrome (Fig. 4-18) Mucopolysaccharidoses, especially Hur-r's, Hunter's, and Morquio's syndromes The mucolipidoses, including gangliosidosis Diastrophic dwarfism of the I_Ly-Maro-aux type when it involves a slightly older individual Cleidocranial dysostosis (Fig. 4-19) The trisomies, especially 17-18 and 13-15 The congenital reticuloendothelial disorers Pseudoachondroplasia tarda Pseudohypoparathyroidism (PHP) (Fig. 44) Pseudopseudohypoparathyroidism (PPHP) Progeria (Fig. 4-25) Gorlin's syndrome or the basal cell nevus yndrome

In this list of disorders it will be noted that the )Mowing may occur at birth and have been previusly described: achondroplasia, the mucopolysacharidoses, the mucolipidoses, and the Lamy-Marteaux syndrome or diastrophic dwarfism. Although diastrophic dwarfism was described in ie section on chondrodysplasias detectable at birth s primarily involving the extremities, other abnorialities become particularly manifest at anywhere

from 2 to 5 years of age and will be described in this group affecting all five areas. Marfan's Syndrome. Marfan's syndrome (arachnodactyly) is basically a disease of collagen and its normal production. It is transmitted as an`autosomal dominant disorder. These patients are tall with elongated and thinned long bones (Fig. 4-16) and poor muscular development, with a hypermotility of the joints. Approximately one-half of the patients have bilateral lens luxations. Extremities. Radiologically (Fig. 4-16), the extremities show markedly elongated and thinned tubular bones, which are most pronounced in the hands and feet (arachnodactyly). The joints are hypermobile, as indicated previously, but contractures, particularly of the fifth digit, are frequent_ Thereis usually a bilateral pes planus deformity with elongation of the great toe accompanied by a bilateral genu valgus deformity. The lower extremities are also excessively elongated, thin, and fragile; but there is no flaring at the metaphyseal ends of the bones. Spine. The 'spine is usually severely scohotic, with the vertical dimension of the lumbar vertebrae particularly elongated. (This is an important point of differentiation from a very similar appearing disorder, homocystinuria, in which the lumbar vertebrae are flattened as in platyspondyly.) Thorax. In the thorax, the ribs are elongated. The posterior ribs are pitched cephaiad and the anterior ribs caudad. Pelvis. In the pelvis, the pelvic cavity appears wide, and a coxa valga is frequent. The hips are painful and stiff, with a protrusio acetabuli frequently present. Congenital dislocations are frequent. Skull. The skull is dolichocephalic, but the patients are not mentally retarded. There is usually an elongated, high-arched palate. The sclerae are typically thin and blue. The ectopic lens of the eyes has already been described. These patients are frequently myopic. Homocystinuria. This condition closely resembles Marfan's syndrome in many respects; but as indicated previously, although scoliosis is present, the vertebrae are not increased in height but tend to be flattened and biconcave. These patients are also usually mentally retarded and subject to seizures. The hips, thoracic cage, and extremities are very similar to those described with Marfan's syndrome, with contractures being very common around the digits, elbows, and knees. Another point of difference from Marfan's syndrome is noted in the metaphyses, which tend to flare, in contrast with Marfan's syndrome, in which no flaring is noted. Homocystine is found in the urine in excessive quantities, and vascular thrombosis is common. In Marfan's syndrome, congenital defects in the heart with an aneurysm of the ascending aorta are noted, and by echocardiography, the valves appear "floppy." In homocystinuria there is early coronary vascular thrombosis and aortic dissection but aneurysm formation is not common. In homocystinuria the elongated bones appear osteoporotic, whereas they are relatively normal in density in Marfan's syndrome. Osteogenesis Imperfecta (Fig. 4-17) (Frogifitas ossium, Lobstein's malady, van der Hoeve's syndrome). Osteogenesis imperfecta is also a disorder of connective tissue affecting the skeleton, ligaments, skin, sclerae, and dentin.

There are two basic forms of this disorder: a congenital variety with a high infant mortality rate and a tarda form, which has a normal life expectancy. In both varieties there is a marked osteoporosis with fragility of the bones of the skeleton, blue sclerae, and imperfect formation of the teeth. Extremities. The long bones very often appear bowed. This usually correlates with the number of fractures encountered and their healing, which is accompanied by
'

considerable
g

deformity.

Spranger

has subdivided this disorder, correlating different clinical findings and enetic patterns of inheritance, and it is possible that new classifications may evolve-

Basically the deformity is due to a defect in bone matrix as well as in the normal circumferential growth of the bones. The cortex is remarkably thin and mechanically weak. The phalanges and other bones often appear so thin as to suggest cystic formation. At times exostoses are present. Because of the thinness of the diaphysis, the metaphyses may actually appear expanded and somewhat hared. Skull. The most prominent findings in the Skull are the late closure of the sutures and the markedly increased number of wormian (sutural) bones. A platybasia is present, and often there is a thin and membranous hydrocephalus. Immature collagen is found in the pulp of the teeth. Mentally the patients are normal. There is a frontal bossing. The sclerae are thin, with abnormal collagen and a blue color. The paranasal sinuses appear large and the teeth imperfect. The spine is usually scoliotic with a platyspondyly and "codfish" vertebrae with indentation of the superior and inferior end plates (Fig. 4-17). Pelvis. The pelvis is usually heart shaped with protrusio acetabuli. Often the hips are dislocated, especially in the congenital variety. Ehlers Danlos Syndrome (Fig. 4-18). This syndrome is another of the collagen disorders. It is familial and is characterized by hyperelasticity and fragility of the skin, with hyperlaxity of the joints and a marked tendency to bleeding. The mesenchymal defect may involve1he eye, the gastrointestinal tract, the bronchopulmonary tree, and the cardiovascular system. At-Mast seven different forms of this disorder have been isolated. The majority of these, however, are autosomal dominant. At times there would . appear to be -an X-linked recessive pattern. The syndrome has also been called cutis hyperelastica and dermatorrheiis. Extremities. Apart from the marked laxity of the joints (Fig. 4-18B), there is often an associated joint effusion or hemarthrosis. Dislocations frequently complicate this disorder. These occur most frequently in the region of the shoulder, the knee, the temporomandibular joints, the radial heads, and the sternoclavicular and acromioclavicular joints. Congenital hip dislocations are also frequent. The relaxed ligamentous structure results in a pes plArius of the feet. In the extremities, the relaxation of the joints frequently results in a fibular head dislocation with genu recurvatum deformity of the knee (Fig. 4-15A). The bones appear osteoporotic. The joint laxity is of course not pathognomonic of this condition, since it also occurs with Marfan's syndrome, Larsen's syndrome, Down's syndrome, and neuromuscular disorders. A somewhat unusual but not pathognomonic finding is a calcification of subcutaneous lesions Thorax. In the thorax, the ribs appear frail but are normal in length.

It is considered that the congenital variety is autosomal recessive and the tarda is autosomal dominant. In the early years there may be an elevated phosphatase. having the appearance of phleboliths due to scarring or hematomas. In a differential diagnosis, hemangiomata and cysticercosis are brought to mind. Spine. The spine demonstrates a severe scoliosis. Skull. In the skull there is a delayed cranial ossification and a high arching of the palate. The face demonstrates bags under the eyes, early wrinkles, blue sclerae, and lop ears. As in the case of Marfan's syndrome, cardiac valves may be seen as "floppy" by echocardiography. Cleidocranial Dysostosis (Fig. 4-19A to F). This disorder is primarily a deficiency in intramembranous bone formation involving the calvaria and clavicles primarily, but other enchondral bone deformations are often present. Extremities. In the upper extremities the distal phalanges appear hypoplastic, especially in the hands and feet, and the diaphyses peripherally are not only osteoporotic but also fragile. Skull. The head is usually large; the facial bones, disproportionately small. Hypertelorism of the orbits is usually present. The nose is saddle shaped, and the bone of the mandible is deficient, with defective or delayed dentition. In the skull the sutures are markedly widened with increased wormian (sutural) bones reminiscent of osteogenesis imperfecta. There may be an associated brachycephaly. The base of the skull is often flattened as a result of platybasia, although the foramen magnum remains large and is often deformed. There is a hypoplasia of the paranasal sinuses, and a high cleft palate is frequently seen. Thorax. The clavicle is particularly affected. Embryologically the clavicle forms from three separate ossification centers, and
in

this disorder one or another of these centers is absent, with total lack of all three centers in about

10 per cent of cases (Fig. 4-19C). Spine. The spine frequently demonstrates a spina bifida with kyphosis, lordosis, or scoliosis. A posterior wedging of the thoracic vertebrae as well as hemivertebrae may be seen. Pelvis. In the pelvis, the bones are poorly developed and there is a wide separation of the pubic symphysis (Fig. 4-19E). Often there is an associated deficiency in the ossification of the Ischia and pubis and hypoplasia of the iliac wings. The heads of the femora often extend beyond the shallow acetabuli, with degenerative changes in the hip joints noted (Fig. 4-19). Mongoloidism (Trisomy 21-22, Down's syndrome) (Fig. 4-20). As indicated in the nomenclature, this is a chromosomal disorder in which the patients have 47 chromosomes instead of 46. Extremities. In the extremities, the changes observed are primarily those in the hands, which appear broad, with clinodactyly of the fifth fingers. Often there are accessory epiphyses of the first and second metacarpals. Throughout the extremities, however, bone maturation appears accelerated: Skull. The skull is small and brachycephalic, with a delayed closure of the sutures and a shortened base of the skull. Mental retardation is usually present. The eyes may slant upward and the iris is surrounded by a silver or gray circle made up of Brushfield's spots. The earlobes are small or absent.

Spine. The cervical spine is often affected, with a dislocation of the atlas due to a congenital anomaly of the cruciate ligament. Thorax. The thorax is unusual. Eleven pairs of ribs are identified, but the twelfth rib is missing. Congenital heart disease is likely to occur, with the most prevalent defect being one in the atrioventricular septum. Pelvis. In the pelvis, the iliac wings appear flared, the acetabuli are flat, the ischiae are tapered, and the iliac index is reduced. Leukemia is a common complication in this disorder. Trisomy 17-18 Syndrome (Fig. 4-21). This is another chromosomal aberration involving a trisomy of chromosome 17 or 18, usually 18. Females are more frequently affected than males. Extremities. In the extremities, the abnormalities are particularly acromelic (involving hands and feet). The lon g itudinal arches of the feet are reversed, impartin,, to them a "rocker-bottom" appearance; a "hammer" great toe is an associated finding. In the hands, the fingers are usually flexed, with the index finger overlapping the third finger and the first metacarpal phalangeat joint being hypoplastic. There is usually an ulnar deviation of the third, fourth, and fifth fingers. Skull. The skull appears elongated (scaphocephalic), and in particular the posterior fossa and Sella turcica are affected. The occiput is prominent. These patients are usually mentally retarded. The ears are markedly abnormal in that they are set very low and are mis-shapen. In the face there is a receding chin, a small mouth, and a hypoplastic mandible. Spine. A scoliosis of the spine is present (Fig. 4-21), and with the deformed vertebrae noted there is associated defective ossification of the ribs and clavicles, which appear wavy and hypoplastic. Thorax. As a result of spinal abnormalities, the thorax is markedly deformed, and the sternum is short. There is usually a congenital cardiac malformation involving either an interventricular septal defect or a patent ductus arteriosus. Pelvis. The pelvis is small and antimongoloid

Figure 4-21. Trisomy 18 syndrome. This 5-day-old infant dem. onstrated malformed ears and palate, a small tongue, and bilateral inguinal hernias. Observe defective ossification of ribs and clavicles with wavy, hypoplastic osseous contours. (From Resnick D, Niwayama G: Diagnosis of Bone and Joint Disorders: With Emphasis on Articular Abnormalities. Philadelphia, W. B. Saunders Co., 1981.) (platypelloid), and the hips are usually dislocated, with the iliac bones appearing thin. Trisomy 13-15 Syndrome (Paton -Syndrome) (Fig. 4-22). Trisomy 13-15 is another chromosomal aberration that occurs more frequently with advanced maternal age. It is less distinctive radiologically than trisomy 17-18, but there is a close resemblance. Extremities. In the hands, polydactyly or syndactyly is usually present. The fingernails of the polydactylic or syndactylic hands are narrow and hyperconvex. Skull. In the head, the forehead appears sloped and the sutures wide. The eyes are small (microphthalmos) with

hypertelorism, present. Colobomas are also noted. Mental retardation is associated, and seizures and deafness are present. A cleft lip and palate are usually also identified. Spine. In the cervical spine, the interpediculate distances are increased. Thorax. The ribs appear "ribbonlike" and resemble those of trisomy 17-18. As in the case of the mongoloids, only eleven pairs of ribs are usually identified. Pelvis. The pelvis has an antimongoloid (platypelloid) configuration. Congenital and renal malformations are frequent, with other associated abnormalities such as intestinal malrotation, umbilical hernia, and horseshoe kidney. Congenital Reticuloendothelial Disorders. There are three reticuloendothelial disorders that come into consideration. All five of the areas enumerated are involved in some way or another. These are (1) erythrogenesis imperfecta, (2) congenital hypoplastic thrombocytopenia, and (3) sickle cell disease (Fig. 4-23). Erythrogenesis Imperfecta. This disorder demonstrates mental retardation. Otherwise no gross evidence of abnormality is detected radiographically. Likewise, the thorax is involved only in that there is frequently an associated congenital heart disease. Basically, it is a tryptophan abnormality with anthranilic acid found in the urine. There is also an associated normocytic normochromic anemia. The major radiographic finding is that of retarded growth, especially manifest in the extremities, and a flexion deformity of the fifth finger of the hands (clinodactyly). Congenital Hypoplastic Thrombocvtopenia. Only one radiographic abnormality is demonstrated. There is usually bilateral absence of the radius. Mental retardation is present. On the other hand, these patients very frequently have a micrognathia and cleft palate. There is usually an associated congenital heart disease. The hematopoietic manifestation is that of a megakarocyte deficiency. Sickle Cell Disease (Fig. 4-23) Extremities. A marked coarsening of the trabeculae related to the marrow disorder is present. This may be manifest in either the upper or the lower extremities. Likewise, very frequently there are bone infarcts manifest in the metaphyses with osteoporosis and a widening of the medullary canals of the diaphyses. The hands may be involved, especially by Salmonella osteomyelitis, producing a rectangular widening of the metacarpals and phalanges and all of the radiologic manifestations of an osteomyelitis. Spine. The spine is involved by a diffuse osteoporosis, wide medullary canals with coarsening of the trabeculae. and an indentation of a rectangular type in the midsection of the end plates of the vertebrae (Fig. 4-23). Pelvis. The pelvis is osteoporotic, with coarsening of the trabeculae, as are virtually all other bones. Skull. The skull often has a "brushlike" appearance extending outwardly toward the scalp from the outer table; the diploe is expanded, and there is a marked thickening of the skull, especially in adults. This appearance closel y resembles that also seen in thalassemia. Indeed, in thalassemia, the appearance of the skull, the spine, and the infarction, especially of the heads of the

femurs, resembles closely that which is found in sickle cell disease. Pseud ohypopa rathyroid ism (PHP) and Pseudopseudohypoparathyroidism (PPHP) (Fig. 4-24). Radiologically, these two conditions are virtually identical in their appearance and differ only in that there is a low serum calcium and a high phosphorus in PHP, since the renal tubules cannot respond to parathormone. Both are characterized especially by (1) dwarfism, (2) brachydactyly. and (3) soft tissue calcification. The biochemical disturbance occurs only in the PHP variety. Skull. The. involvement of the calvaria and its contents is minimal. The major manifestations are a thick calvaria and calcified basal ganglia. There is usually mental retardation, and corneal and lens opacities may be identified. An abnormal dentition is present. Pelvis. In the pelvis, there may be either a coxa valga or a var y deformity, and in the entire skeleton osteoporosis or sclerosis may be manifest. Extremities. In the extremities, the maturation of the bones is accelerated, with a disproportionate shortening of the metacarpals and phalanges. The third, fourth, or fifth metatarsals or metacarpals are shorter than the adjoining ones. In the extremities, soft tissue calcifications are identified to the extent that they have the appearance of exostoses of the diaphyses (Fig. 4-24). Progeria (Fig. 4-25). In progeria, also called the Hutchinson-Gilford syndrome, the infant is usually' relativelynormal until approximatelyI year of age. most significant findings thereafter are dwarfism, premature aging, and early death. Extremities. The main findings are an overconstriction of the long bones with a prominence of the knees. The elbows likewise appear to be enlarged, especially in the region of the capitulum and head of the radius. In the hands, there is often a resorption of the terminal tufts. Bone maturation, however, is normal. Pelvis. There is usually a bilateral coxa valga deformity. Spine. The vertebrae retain their infantile central notching anteriorly and posteriorly. Thorax. The clavicles appear small. The chest is narrow, and there is a progressive resorption of the clavicles and the ribs in many instances. Skull. The facies are rather characteristic in that there is a beaked nose, receding chin, and baldness. The calvaria demonstrate thin fontanelles that are either open or closed with wormian bones seen in excess. The sells turcica is also enlarged. Basal-cell Nevus Syndrome (Gorlin's Syndrome) (Fig. 4-26). The main diagnostic criteria for this syndrome are multiple basal cell epitheliomas throughout the skin of the body, mandibular cysts appearing radiologically, and calcified mesenteric cysts. Extremities. The manifestations in the extremities are chiefly in the hands and feet (acromelic) with a brachydactyly noted. Thorax. There is a great tendency for bifidity of the ribs. Spine. A scoliosis may be quite marked. Skull. There is usually a calcification of the falx cerebri. It is possible that a genetic deletion in chromosome 19 or 20 is responsible for this appearance. Pseudoachondroplasia. This entity has already been considered (Fig. 4-12). It appears in this category

because of a variability in its manifestations. Many investigators have graded this entity from 1 to 4 as a result. Moreover, the skeletal abnormalities increase during childhood but appear to assume a more normal appearance in adulthood. If one were to describe the usual appearance, the skull, face, and thorax would be considered normal. The main abnormalities are found in the spine and pelvis. Spine. The spine is characterized by a platyspondyly with the interpediculate distances being normal, unlike achondroplasia, in which interpediculate distances are diminished in the lumbar region. There is usually an associated scoliosis, and posterior arch defects are common. Pelvis. In the pelvis, the acetabuli appear irregular, as do the heads of the femurs. There is often a protrusio acetabuli and coxa vara preseht, and in some instances hip dislocation may follow. Extremities. The extremities are involved primarily in that there is a rhizomelic shortening with flaring of the epiphyses and metaphyses and a tendency to fragmentation. It is thought that this probably represents a lipoprotein or glycoprotein abnormality. The lards form of this disease is autosomal recessive. Pelvis. There is usually a bilateral coxa valga deformity. Spine. The vertebrae retain their infantile central notching anteriorly and posteriorly. Thorax. The clavicles appear small. The chest is narrow, and there is a progressive resorption of the clavicles and the ribs in many instances. Skull. The facies are rather characteristic in that there is a beaked nose, receding chin, and baldness. The calvaria demonstrate thin fontanelles that are either open or closed with wormian bones seen in excess. The sells turcica is also enlarged. Basal-cell Nevus Syndrome (Gorlin's Syndrome) (Fig. 4-26). The main diagnostic criteria for this syndrome are multiple basal cell epitheliomas throughout the skin of the body, mandibular cysts appearing radiologically, and calcified mesenteric cysts. Extremities. The manifestations in the extremities are chiefly in the hands and feet (acromelic) with a brachydactyly noted. Thorax. There is a great tendency for bifidity of the ribs. Spine. A scoliosis may be quite marked. Skull. There is usually a calcification of the falx cerebri. It is possible that a genetic deletion in chromosome 19 or 20 is responsible for this appearance. Pseudoachondroplasia. This entity has already been considered (Fig. 4-12). It appears in this category because of a variability in its manifestations. Many investigators have graded this entity from 1 to 4 as a result. Moreover, the skeletal abnormalities increase during childhood but appear to assume a more normal appearance in adulthood. If one were to describe the usual appearance, the skull, face, and thorax would be considered normal. The main abnormalities are found in the spine and pelvis. Spine. The spine is characterized by a platyspondyly with the interpediculate distances being normal, unlike

achondroplasia, in which interpediculate distances are diminished in the lumbar region. There is usually an associated scoliosis, and posterior arch defects are common. Pelvis. In the pelvis, the acetabuli appear irregular, as do the heads of the femurs. There is often a protrusio acetabuli and coxa vara preseht, and in some instances hip dislocation may follow. Extremities. The extremities are involved primarily in that there is a rhizomelic shortening with flaring of the epiphyses and metaphyses and a tendency to fragmentation. It is thought that this probably represents a lipoprotein or glycoprotein abnormality. The lards form of this disease is autosomal recessive.

NORMAL SKULL; OTHER FOUR SKELETAL AREAS ABNORMAL Most of the entities in this group have already been considered, since they represent chondrodysplasias that may be detectable at birth or at a later period in the infant or even adolescent. Included here are pseudoachondroplasia (Fig. 4-12), meta-tropic dwarfism (Fig. 4-11), which has been described under those chondrodysplasias detectable at-birth; mucopolysaccharidoses such as Scheie's syndrome; spondyloepiphyseal dysplasia (Fig. 4-5) and Turner's syndrome. This entity has not been previously described. Turner's Syndrome (Figs. 4-27 and 4-28). This syndrome, also called Noonan's syndrome, is due to a chromosomal sex-linked disorder. It is a monosomy of the X chromosome (XO) in a chromatin-negative female. This is therefore a gonadal dysgenesis (Keats and Burns). This would indicate that it is one of a group of syndromes involvingeither an abnormality or aplasia of the gonads. This would imply that there is a normal number of autosomal chromosomes but only one sex chromosome. Although most fetuses with this abnormality are aborted in the first trimester of pregnancy, if a live infant is produced, the subsequent development of the child or adolescent is abnormal. The ovaries are fibrotic, and a primary amenorrhea is present with an absence of the secondary sex characteristics of a female. In the child there is usually a lymphedema of the -lower extremities (Fi g. 4-27), a congenital webbing of the neck, a cubitus valgus, and a tendency toward infantilism. Extremities. As noted in Figures 4-27 and 4-28, the specific skeletal areas involved are the hands, wrists, and knees. There is a diffuse osteoporosis, a delay in the fusion of the ossification centers, and a decrease in the carpal angle, as shown. There is a medial tibial exostosis, with compensatory overgrowth (or undergrowth) of the medial femoral condyle. The distal phalanges tend to be shaped like a drumstick, and the metacarpals, especially the third and fourth, have flat heads. The undergrowth of the fourth and fifth metacarpals has been referred to as the "metacarpal sign of Turner's syndrome," although it is not specific. Thorax. In the chest, the nipples are spaced broadly apart. Spine. There is usually a hypoplasia of the first cervical segment. Skull. There is a tendency to hypertelorism and eighth cranial nerve deafness. Hypoplasia of the mandible may also occur. In the urine there is usually an elevation of the gonadotropins, especially in individuals who grow to adulthood. Some investigators have referred to Noonan's syndrome as a pseudo-Turner's syndrome, since apparently it can occur in both males and females. Chromosomal studies and chromatin smears are normal, but mental retardation is common. In the latter syndrome, cardiac malformations are often present, most frequently an atrial septal defect or pulmonic stenosis, as opposed to coarctation of the aorta, which is often associated with Turner's syndrome. In Turner's syndrome there is often an associated renal anomaly, such as malrotation or a horseshoe kidney. Neither of these findings is present in Noonan's syndrome. ABNORMAL THORAX, EXTREMITIES, AND PELVIS In this group of disorders the spine and skull are usually not involved. Included are the HoltOram syndrome, hereditary onycho-osteodysplasia (HOOD syndrome), and gonadal dysgenesis, which may include either Turner's or Klinefelter's syndrome.

Holt-Dram Syndrome (Upper Limb-Cardiovascular Syndrome). The extremities, especially the upper extremities, are affected with congenital anomalies. There is usually an associated congenital heart lesion, especially of the atrial septal defect type. Hereditary Onycho-Osteodysplasia (HOOD Syndrome) (Fig. 4-29). This syndrome has occasionally been referred to as Foong's syndrome. It is especially characterized by dysplastic fingernails, hypoplastic or absent patellae, iliac horns, and associated renal dysplasia with proteinuria. There is usually an associated foot deformity with flexion contractures and muscle hypoplasia. The elbows, pelvis, and knees are often involved. Pelvis. The noteworthy finding in regard to the pelvis is the presence of iliac horns (Fi g. 4-29). The iliac crests appear flared. Extremities. In association with the subluxation of the patella, which may lbg either hypoplastic or aplastic, there is often a hyperplasia and increased size of the medial femoral condyle, whereas the lateral femoral condyle appears diminished in size. The radial head is often hypoplastic. This disorder is thought to be autosomal dominant and follows closely ABO blood group inheritance. There is sometimes an associated abnormal pigmentation of the iris and a Plummer-Vinson syndrome with a smooth tongue, hyperchromic anemia, and hypochlorhydria. ABNORMAL EXTREMITIES, THORAX, PELVIS, AND SKULL; OCCASIONALLY MINIMAL INVOLVEMENT OF THE SPINE ' The various entities that may fall into this category are some that have already been considered, but others are to be described. Those chondrodysplasias or abnormalities characterized in this fashion are the following: 1. Pseudoachondroplasias (owing to their heterogeneous appearance, these have already been described) (Fig. 412) 2. Cornelia de Lange syndrome 3. Some of the Craniostenosis syndromes with syndactylism (Apert's I and Apert's 11 the ApertCrouzon syndrome) 4. The Saethre-Chotzen syndrome 5. Carpenter's syndrome 6. Pfeiffer's syndrome (familial acrocephalosyndactyly) (apart from congenital fusions of the cervical and lumbar vertebrae that may occur) At times the trisomies, such as trisomy 17-18 and 13-15, may also fall into this category, but these have already been described (Figs. 4-21 and 4-22) . Cornelia de Lange Syndrome (Lee and Kenny) (Fig. 4-30). This syndrome has also been called typos degenerativus amstelodamensis. It is characterized by dwarfism, mental retardation, skeletal abnormalities, and a rather characteristic facies. Skull. The facies show a low hairline with heavy eyebrows and a thin upper lip that is concave cephalad, producin g a masklike appearance. The skull is usually microcephalic. There may be a spur on the mandible, especially on its anterior, inferior, midline surfaces. Extremities. The proximal parts of the extrem- ities are usually normal. The distal or acromelic portions of the extremities show shortness with dwarfism and dislocations, especially of the elbow. The hips are also occasionally dislocated. The upper extremities especially are hypoplastic, and the radial head is frequently subluxed. The hands appear hypoplastic with a clinodactyly of the fifth finger. There is a diffuse retarded maturation of the bones with a supracondylar spur at times noted on the humerus. There may be segmentation anomalies, especially in the hand, with development of fewer than five metacarpals. Craniostenosis Syndromes with Syndactylism. There are four syndromes ordinarily included among these: (1) Apert's I and II (Fig. 4-31), (2) the Saethre-Chotzen syndrome, (3) Carpenter's syndrome (Fig. 4-32), and (4) Pfeiffer's syndrome. Apert's I and 11. The predominant findings in Apert's I and II are in the skull, hands, and feet. Skull. Scaphocephaly is usually present, with premature closure of the sutures and associated mental retardation. Extremities. Syndactylism of the hands, feet, carpals, and tarsals is a predominant feature. Apart from these findings in the skull, the facies are unusual in that there is a hypertelorism with bulging eyes, high forehead, and short nose. The maxillae are often hypoplastichence the term "Apert-Crouzon's syndrome." Spine. A synostosis may also occur in the neck and is progressive among the bodies of the vertebra and spinous processes. Thus the cervical spine may also be involved, differing in this regard from the other entities in this group. The disease is considered to be autosomal dominant.

Clinically, the syndactyly may give rise to hands with the appearance of a "rosebud" (Fig. 4-31B). Saethre-Chotzen Syndrome. There is a predominance of acrocephalosyndactyly in the SaethreChotzen syndrome and mild changes in the skeleton otherwise. There is diffuse growth retardation, and there may be a cutaneous syndactyly, but without involvement of the bones proper. Skull. In the skull, apart from the premature closure of the sutures, the base of the skull is low and the sella turcica is abnormally vertical and short, probably in relation to a sphenoccipital synchondrosis. The mandible is usually short, and the frontal and mastoid air cells are either aplastic or hypoplastic. Carpenter's Syndrome (Acrocephalopolysyndactyly) (Fig. 4-32). craniosynostosis, polydactyly, syndactyly, and variable dwarfism are noted in Carpenter's syndrome. Skull. The skull may have an abnormal shape with trigonocephaly or dolicocephaly, but the changes are not nearly as severe as in Apert's syndrome. Usually syndactyly is due to soft tissue fusion. There is a clinodactyly of the fifth fingers and short middle phalanges. Obesity is also present. It is considered to be autosomal recessive, but when autosomal dominant, it is Noack's syndrome. Pfeiffer's Syndrome (Familial Acrocephalosyndactyly). This syndrome too is similar to Apert's as far as the calvaria are concerned, but there is an associated hypertelorism and a flat nasal bridge. There is a tendency to congenital fusions of the cervical and lumbar vertebrae in this entity also. Apart from the syndactylism and tendency to varus great toes, there is occasionally a coalition of the tarsal bones and a hypoplasia of the elbow and shoulder. It is noteworthy that there is a selective shortenin g of the middle phalanges of the index and fifth finger, giving rise to clinosyndactyly.