American Journal of Medical Genetics 42:19-21 (1992)
Ectopia Lentis and Aortic Root Dilatation in Congenita1 Contractur a1 A r achnodactyly Erawati Bawle and Mary Helen Quigg Division of Genetic and Metabolic Disorders, Department of Pediatrics (EB.) and Division of Reproductive Genetics, Department of Obstetrics and Gynecology (M.H.Q.), Wayne State University, Detroit, Michigan
Congenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis,and a distinct “crumpled ear” deformity. While the disorder is similar to Marfan syndrome,it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echocardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients.
KEY WORDS: Marfan syndrome, aortic aneurysm, autosomal dominant inheritance INTRODUCTION Beals and Hecht [1971]proposed the name congenital contractural arachnodactyly (CCA)for a pleiotropic condition of congenital contractures at small and large joints, thin narrow limbs, arachnodactyly, scoliosis, “crumpled” or abnormal external ears, and autosomal dominant inheritance. Previously, similar cases had been called arachnodactyly with arthrogryposis but Received for publication December 4, 1990,revision received May 28, 1991. Address reprint request to Dr. Erawati Bawle, Genetic and Metabolic Disorders, Children’s Hospital of Michigan, 3901 Beaubien, Detroit, MI 48201.
0 1992 Wiley-Liss, Inc.
may have been examples of CCA [Reeve et al., 1959; Traisman and Johnson, 19541. The literature on this subject after Beals and Hecht’s [19711 original description contains reports of CCA cases with mitral valve prolapse, aortic root dilatation, mitral regurgitation, congenital heart defects, keratoconus, and myopia but no lens dislocation. [Gruber et al., 1978; Bass et al., 1981; Anderson et al., 1984; Shikata et al., 1987; Huggon et al., 19901. We report on a patient with CCA and bilateral ectopia lentis and aortic root dilatation.
CLINICAL REPORT C.W., a black boy, was born at term of an uncomplicated pregnancy and breech delivery. He weighed 3,180 g; BL was 47.5 cm. There were no neonatal complications, but joint contractures were noted. At one month a geneticist made the diagnosis of arthrogryposis multiplex congenita on the basis of flexion contractures at elbows, knees, hips, and interphalangeal joints of fingers and toes. Chromosomes were normal, (46,XY). Radiographs of the entire skeleton showed anterior bowing of both femora and medial bowing of both tibiae, radii and ulnae. Parents were healthy, and had no deformities. The mother was 19 years old and the father 23 years old. The patient’s only sib, a 2-year-old brother, was normal. The family history was unremarkable. He was evaluated by us a t 9 years. Progressive thoracic scoliosis was fixed surgically at 7 years, and he was using glasses for myopia. He was doing well in 3rd grade and could write legibly despite finger contractures. He was 144 cm tall (10th centile) and had a weight of 21 kg (5th centile). At 16 months his length had been a t the 95th centile; the later centile drop was due to scoliosis. Arm span and upper segmentAowersegment ratio could not be measured because of contractures. He also had downslanting palpebral fissures, high-arched palate, micrognathia, and “crumpled ears (Fig. 1,taken at age 12 years). Skeletal findings included: marked thoracic scoliosis with secondary chest deformity, flexion contractures at metacarpo-phalangeal, interphalangeal, (Fig. 2) elbow, knee, and hip joints, inability to fully supinate both forearms, arachnodactyly, thin, “wasted” limbs, normal deep tendon reflexes, and soft systolic murmur.
20
Bawle and Quigg
Fig. 1. (a, b) Facial appearance at 12 years.
Fig. 2. Multiple contractures of hand joints.
Ophthalmic evaluation showed bilateral inferior and nasal subluxation of lenses, left more than the right (Fig. 3). Due to severely compromised vision o.s., the lens was removed with subsequent retinal detachment. His vision is drastically reduced on the left. Echocardiography showed mitral valve prolapse, and aortic root diameter of 2.3 cm as compared with the predicted 1.8to 2.0 cm for a boy with a body surface area of 0.9m2and aortic root dimension of 2.4 cm as compared with normal of less than 2.2 cm. Urine amino acid and metabolic screening did not show homocystinuria.
DISCUSSION Marfan syndrome and CCA have been differentiated on the basis of lack of severe ocular or cardiovascular
complications in CCA. However, a review of the recent literature on CCA showed that cardiovascular complications have been noted by many authors [Bell and Whellar, 1985; Shikata et al., 1987; Gruber et al., 1978; Anderson et al., 1984; Huggon et al., 19901 and eye manifestations, such as myopia and keratoconus, were noted by others [Basset al., 1981; Anderson et al., 1984; Huggon et al., 19901. No cases of dislocation of lenses or retinal detachment were noted. Only 1patient reported by Reeve et al. [19591as having “Marfan syndrome and arthrogryposis” is similar to ours. That infant with ectopia lentis in right eye died at 3 months of an acute febrile illness and autopsy showed dilatation of the ascending aorta. The ocular and echocardiographic surveillance of CCA patients does not seem to occur uniformly as illustrated by the following case reports [Currarino and Friedman, 1986; Bell and Whellar, 1985; Arroyo et al., 1985; Lowry and Guichon, 1972; Travis and Shaw, 19851. This may be because there are no reports of lens dislocations with CCA and the relationship of CCA to Marfan syndrome remains unclear. It is noteworthy that Morse et al. [1990]noted congenital contractures in 64% of their infantile Marfan syndrome patients and in 47% of literature cases. Hecht [19811has discussed that CCA and Marfan syndrome are examples either of genetic heterogeneity or of pleiotropy. The issue may be resolved when molecular or genetic defects of these conditions are discovered. We reiterate the advice given by Pyeritz et al. [19791 and Morse et al. [1990]that patients with CCA shouldbe monitored closely by detailed eye examination and echocardiography in the same manner as patients with Marfan syndrome.
Contractural Arachnodactyly and Ectopia Lentis
21
Fig. 3. (a, b) Subluxation of lenses, both eyes.
REFERENCES Anderson RA, Koch S, Camerini-Otero RD (1984):Cardiovascularfindings in congenital contractural arachnodactyly: Report of an affected kindred. Am J Med Genet 18265-271. Arroyo MR, Weaver DD, Beals RK (1985): Congenital contractural arachnodactyly. Clin Genet 27:570-581. Bass HN, Sparkes RS, Crandall BF, Marcy SM (1981): Congenital contractural arachnodactyly, keratoconus, and probable Marfan syndrome in the same pedigree. J Pediatr 98:591-593. Beak RK, Hecht F (1971): Congenital contractural arachnodactyly. J Bone Joint Surg 53A.3987-993. Bell RE, Wheller JJ (1985):Cardiac defects in a patient with congenital contractural arachnodactyly. South Med J 78:742-743. Currarino G, Friedman JM (1986):A severe form ofcongenital contractural arachnodactyly. Am J Med Genet 25763-773. Gruber MA, Graham TP, Engel E, Smith C (1978):Marfan syndrome with contractural arachnodactyly and severe mitral regurgitation in a premature infant. J Pediatr 93:80-82. Hecht F (1981): Uncommon children and common care. J Pediatr 98~594-595.
Huggon IC, Burke JP, Talbot J F (1990):Contractural arachnodactyly with mitral regurgitation and iridodonesis.Arch Dis Child 65:317319. Lowry RB, Guichon VC (1972): Congenital contractural arachnodactyly: A syndrome simulating Marfan’ssyndrome.Canad Med Assoc J 107:531-533. Morse RP, Rockenmacher S,Pyeritz RE, Sanders SP, Bieber FR, Lin A, MacLeod P, Hall B, Graham J r JM (1990):Diagnosis and management of infantile Marfan syndrome. Pediatrics 86:888-895. F‘yeritz RE, Murphy EA, McKusick VA (1979): Clinical variability in the Marfan syndrome(s). Birth Defects XV (5B):155-178. Reeve R, Silver HK, Ferrier P (1959):Marfan’s syndrome (arachnodactyly) with arthrogryposis (amyoplasia congenital. AJDC 99:117122. Shikata J , Yamamuro T, Mikawa Y, Hirokazu I, Nishimura N (1987): Kyphoscoliosis in congenital contractural arachnodactyly. A case report. Spine 121055-1058. Traisman HS, Johnson FR (1954): Arachnodactyly associated with aneurysm of the aorta. AJDC 87:156-165. Travis RC, Shaw DC (1985):Congenital contractural arachnodactyly. Br J Radio1 58:1115-1117.
Ectopia Lentis and Aortic Root Dilatation in Congenita1 Contractur a1 A r achnodactyly Erawati Bawle and Mary Helen Quigg Division of Genetic and Metabolic Disorders, Department of Pediatrics (EB.) and Division of Reproductive Genetics, Department of Obstetrics and Gynecology (M.H.Q.), Wayne State University, Detroit, Michigan
Congenital contractural arachnodactyly (CCA) was described by Beals and Hecht as an autosomal dominant disorder distinct from Marfan syndrome and comprising joint contractures, arachnodactyly, scoliosis,and a distinct “crumpled ear” deformity. While the disorder is similar to Marfan syndrome,it was split from it due to the distinct physical appearance of the patients and, more importantly, the lack of heart and eye findings. Since the original report, several CCA patients have been found to have mitral valve prolapse, structural cardiac anomalies, and occasionally aortic root dilatations similar to those seen in Marfan syndrome. We report on a patient with CCA with bilateral ectopia lentis and aortic root dilatation. Our review of the literature of CCA showed that serial echocardiography and careful eye examinations have not become a standard of medical practice in this condition. Partly this may be due to a lack of documented cases of CCA having severe ectopia lentis and cardiac complications. This patient underscores the need for periodic eye and echocardiographic evaluations of all CCA patients.
KEY WORDS: Marfan syndrome, aortic aneurysm, autosomal dominant inheritance INTRODUCTION Beals and Hecht [1971]proposed the name congenital contractural arachnodactyly (CCA)for a pleiotropic condition of congenital contractures at small and large joints, thin narrow limbs, arachnodactyly, scoliosis, “crumpled” or abnormal external ears, and autosomal dominant inheritance. Previously, similar cases had been called arachnodactyly with arthrogryposis but Received for publication December 4, 1990,revision received May 28, 1991. Address reprint request to Dr. Erawati Bawle, Genetic and Metabolic Disorders, Children’s Hospital of Michigan, 3901 Beaubien, Detroit, MI 48201.
0 1992 Wiley-Liss, Inc.
may have been examples of CCA [Reeve et al., 1959; Traisman and Johnson, 19541. The literature on this subject after Beals and Hecht’s [19711 original description contains reports of CCA cases with mitral valve prolapse, aortic root dilatation, mitral regurgitation, congenital heart defects, keratoconus, and myopia but no lens dislocation. [Gruber et al., 1978; Bass et al., 1981; Anderson et al., 1984; Shikata et al., 1987; Huggon et al., 19901. We report on a patient with CCA and bilateral ectopia lentis and aortic root dilatation.
CLINICAL REPORT C.W., a black boy, was born at term of an uncomplicated pregnancy and breech delivery. He weighed 3,180 g; BL was 47.5 cm. There were no neonatal complications, but joint contractures were noted. At one month a geneticist made the diagnosis of arthrogryposis multiplex congenita on the basis of flexion contractures at elbows, knees, hips, and interphalangeal joints of fingers and toes. Chromosomes were normal, (46,XY). Radiographs of the entire skeleton showed anterior bowing of both femora and medial bowing of both tibiae, radii and ulnae. Parents were healthy, and had no deformities. The mother was 19 years old and the father 23 years old. The patient’s only sib, a 2-year-old brother, was normal. The family history was unremarkable. He was evaluated by us a t 9 years. Progressive thoracic scoliosis was fixed surgically at 7 years, and he was using glasses for myopia. He was doing well in 3rd grade and could write legibly despite finger contractures. He was 144 cm tall (10th centile) and had a weight of 21 kg (5th centile). At 16 months his length had been a t the 95th centile; the later centile drop was due to scoliosis. Arm span and upper segmentAowersegment ratio could not be measured because of contractures. He also had downslanting palpebral fissures, high-arched palate, micrognathia, and “crumpled ears (Fig. 1,taken at age 12 years). Skeletal findings included: marked thoracic scoliosis with secondary chest deformity, flexion contractures at metacarpo-phalangeal, interphalangeal, (Fig. 2) elbow, knee, and hip joints, inability to fully supinate both forearms, arachnodactyly, thin, “wasted” limbs, normal deep tendon reflexes, and soft systolic murmur.
20
Bawle and Quigg
Fig. 1. (a, b) Facial appearance at 12 years.
Fig. 2. Multiple contractures of hand joints.
Ophthalmic evaluation showed bilateral inferior and nasal subluxation of lenses, left more than the right (Fig. 3). Due to severely compromised vision o.s., the lens was removed with subsequent retinal detachment. His vision is drastically reduced on the left. Echocardiography showed mitral valve prolapse, and aortic root diameter of 2.3 cm as compared with the predicted 1.8to 2.0 cm for a boy with a body surface area of 0.9m2and aortic root dimension of 2.4 cm as compared with normal of less than 2.2 cm. Urine amino acid and metabolic screening did not show homocystinuria.
DISCUSSION Marfan syndrome and CCA have been differentiated on the basis of lack of severe ocular or cardiovascular
complications in CCA. However, a review of the recent literature on CCA showed that cardiovascular complications have been noted by many authors [Bell and Whellar, 1985; Shikata et al., 1987; Gruber et al., 1978; Anderson et al., 1984; Huggon et al., 19901 and eye manifestations, such as myopia and keratoconus, were noted by others [Basset al., 1981; Anderson et al., 1984; Huggon et al., 19901. No cases of dislocation of lenses or retinal detachment were noted. Only 1patient reported by Reeve et al. [19591as having “Marfan syndrome and arthrogryposis” is similar to ours. That infant with ectopia lentis in right eye died at 3 months of an acute febrile illness and autopsy showed dilatation of the ascending aorta. The ocular and echocardiographic surveillance of CCA patients does not seem to occur uniformly as illustrated by the following case reports [Currarino and Friedman, 1986; Bell and Whellar, 1985; Arroyo et al., 1985; Lowry and Guichon, 1972; Travis and Shaw, 19851. This may be because there are no reports of lens dislocations with CCA and the relationship of CCA to Marfan syndrome remains unclear. It is noteworthy that Morse et al. [1990]noted congenital contractures in 64% of their infantile Marfan syndrome patients and in 47% of literature cases. Hecht [19811has discussed that CCA and Marfan syndrome are examples either of genetic heterogeneity or of pleiotropy. The issue may be resolved when molecular or genetic defects of these conditions are discovered. We reiterate the advice given by Pyeritz et al. [19791 and Morse et al. [1990]that patients with CCA shouldbe monitored closely by detailed eye examination and echocardiography in the same manner as patients with Marfan syndrome.
Contractural Arachnodactyly and Ectopia Lentis
21
Fig. 3. (a, b) Subluxation of lenses, both eyes.
REFERENCES Anderson RA, Koch S, Camerini-Otero RD (1984):Cardiovascularfindings in congenital contractural arachnodactyly: Report of an affected kindred. Am J Med Genet 18265-271. Arroyo MR, Weaver DD, Beals RK (1985): Congenital contractural arachnodactyly. Clin Genet 27:570-581. Bass HN, Sparkes RS, Crandall BF, Marcy SM (1981): Congenital contractural arachnodactyly, keratoconus, and probable Marfan syndrome in the same pedigree. J Pediatr 98:591-593. Beak RK, Hecht F (1971): Congenital contractural arachnodactyly. J Bone Joint Surg 53A.3987-993. Bell RE, Wheller JJ (1985):Cardiac defects in a patient with congenital contractural arachnodactyly. South Med J 78:742-743. Currarino G, Friedman JM (1986):A severe form ofcongenital contractural arachnodactyly. Am J Med Genet 25763-773. Gruber MA, Graham TP, Engel E, Smith C (1978):Marfan syndrome with contractural arachnodactyly and severe mitral regurgitation in a premature infant. J Pediatr 93:80-82. Hecht F (1981): Uncommon children and common care. J Pediatr 98~594-595.
Huggon IC, Burke JP, Talbot J F (1990):Contractural arachnodactyly with mitral regurgitation and iridodonesis.Arch Dis Child 65:317319. Lowry RB, Guichon VC (1972): Congenital contractural arachnodactyly: A syndrome simulating Marfan’ssyndrome.Canad Med Assoc J 107:531-533. Morse RP, Rockenmacher S,Pyeritz RE, Sanders SP, Bieber FR, Lin A, MacLeod P, Hall B, Graham J r JM (1990):Diagnosis and management of infantile Marfan syndrome. Pediatrics 86:888-895. F‘yeritz RE, Murphy EA, McKusick VA (1979): Clinical variability in the Marfan syndrome(s). Birth Defects XV (5B):155-178. Reeve R, Silver HK, Ferrier P (1959):Marfan’s syndrome (arachnodactyly) with arthrogryposis (amyoplasia congenital. AJDC 99:117122. Shikata J , Yamamuro T, Mikawa Y, Hirokazu I, Nishimura N (1987): Kyphoscoliosis in congenital contractural arachnodactyly. A case report. Spine 121055-1058. Traisman HS, Johnson FR (1954): Arachnodactyly associated with aneurysm of the aorta. AJDC 87:156-165. Travis RC, Shaw DC (1985):Congenital contractural arachnodactyly. Br J Radio1 58:1115-1117.
