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640 Med Genet 1994;31:640-643

Syndrome of the month J Med Genet: first published as 10.1136/jmg.31.8.640 on 1 August 1994. Downloaded from

Congenital contractural (Beals syndrome)

Denis Viljoen

Abstract delineated by Beals and Hecht in 1971.1 The Congenital contractural arachnodactyly eponymous designation "Beals syndrome" is (CCA) is an autosomal dominant dis- now usually applied to patients with the con- order akin to, but usually less severe dition. than, . The clinical At least 40 families with more than 120 features are marfanoid habitus, arach- affected members have been reported to date. nodactyly, crumpled ears, camptodac- The classical clinical features of CCA are vari- tyly of the fingers and adducted thumbs, able and tend to overlap with those of Marfan mild contractures of the elbows, , syndrome; interestingly, it is contended that and , and mild muscle hypoplasia the original patient described by Marfan actu- especially of the calf muscles. Many ally had CCA.2 Distinct defects in patients have and mitral both disorders have recently been elucidated, valve prolapse and, very occasionally, thereby allowing differentiation of the two aortic root dilatation and ectopia lentis conditions on a molecular basis.35 have been described. Linkage to a gene coding for fibrillin on chromosome 5q23- 31 has been shown in several kindreds. Clinical features The prognosis for a normal lifespan is The manifestations in CCA are summarised in good and improvement in joint contrac- the table. tures is usual.

(J7 Med Genet 1994;31:640-643) HABITUS Affected persons tend to have a distinctive http://jmg.bmj.com/ Marfan-like appearance, being tall and thin Congenital contractural arachnodactyly with a span which exceeds their adult height (CCA) is an autosomal dominant disorder first measurement by more than 5 cm. on October 1, 2021 by guest. Protected copyright. Review of the clinical manifestations ofpatients with CCA Clinicalfeatures Review of 29 Review of 13 Total Percentage families by Ramos families reported Arroyo et a16 after 1985 Craniofacial Crumpled ear 40/61 39/43 79/104 76-0 Micrognathia 11/47 10/32 21/79 26-6 Highly arched palate 15/53 10/35 25/88 28-4 Cranial deformity 18/45 6/38 24/83 28-9 Extremities Limited extension of Elbows 54/64 40/45 94/109 86-2 Knees 49/62 38/45 87/107 81-3 Hips 18/62 10/45 28/107 26-2 Camptodactyly 57/64 38/45 85/109 78-0 Arachnodactyly 55/64 39/45 94/109 86-2 Adducted thumbs 23/47 19/43 42/90 46-7 / 31/62 17/43 48/105 45-7 Club 22/59 6/42 28/101 27-7 Bowed long bones 11/44 14/35 25/79 31 7 Department of Muscle hypoplasia 33/55 30/42 63/97 64-9 Human Genetics, Contractural University of Cape improvement 45/48 32/40 77/88 87-5 Town Medical School, Observatory 7925, Other organ systems Cape Town, South Heart 9/61 19/42 28/103 27-2 Africa Eye - 9/43 9/43 209 D Viljoen Congenital contractural arachnodactyly (Beals syndrome) 641

CRANIOFACIAL FEATURES MUSCULOSKELETAL ANOMALIES A characteristic feature in CCA is a "crum- Symmetrical contractures of small and large pled" appearance of the external ears6 (fig 1) in joints are frequent in CCA. The fingers are

which the upper helix is folded, the crura are usually long and narrow at birth with flexion J Med Genet: first published as 10.1136/jmg.31.8.640 on 1 August 1994. Downloaded from prominent, and the concha is shallow. This contractures of the proximal interphalangeal sign, or variations thereof, was evident in 76% joints (fig 2) and the are long and slender. of published cases.*'7 Less frequent craniofa- The thumb tends to be adducted into the cial features are mild micrognathia (26-6%), palm. Camptodactyly usually improves with highly arched palate (28-4%), and cranial ab- age. Contractures of major joints are often normalities including , brachy- present at birth with the elbows (86-2%), cephaly, , and frontal bossing knees (81-3%), and hips (26-2%) predomi- (28-9%). nantly involved. The ankles may be held in valgus and, peculiarly, have excessive dorsal flexion. Mild talipes equinovarus is evident in a proportion of patients at birth (31-7%) but responds rapidly to physiotherapy. Sternal deformities are frequent (fig 3). Spinal mal- alignment is present in more than 45% of affected persons (fig 4) and, unlike the joint contractures, tends to be progressive. Bowing of the long bones with radiological osteopenia is a feature in a few cases and is said also to worsen with age. Hypoplasia of the muscles, particularly those ofthe lower leg, is a frequent finding (fig 4).

CARDIOVASCULAR MANIFESTATIONS Until the recent discovery of the separate gene defects in CCA and Marfan syndrome (MS),"5 considerable debate has centred on differentia- tion of the two disorders on the basis of absence or presence of severe cardiovascular involve- ment. There remains considerable confusion as to whether aortic root dilatation and aneurysm formation in a tall, slender person with crump- led ears and joint contractures represents CCA or MS. Such diagnostic dilemmas will be

resolved once the specific intragenic defects of http://jmg.bmj.com/ each condition are fully elucidated. In the in- terim, it can be accepted that mitral valve Figure 1 "Crumpled" ears in a patient with CCA prolapse with regurgitation'0 is often a compon- (reproduced from Viljoen D, et al, Clin Genet 1991;31:181-8). ent ofpatients with CCA whereas patent ductus arteriosus, ventriculoseptal defect, and bicuspid aortic valve'4 are occasionally present. Persons with joint contractures, eye manifestations, and on October 1, 2021 by guest. Protected copyright.

Figure 2 Flexion contractures in a young boy with Beals syndrome (reproduced from Beighton P, Inherited disorders of the skeleton, 1988: 407-8). 642 Viljoen Differential diagnosis The disorder most akin to CCA is Marfan syndrome. Differentiation is critical as the latter is potentially lethal, has considerable morbidity, and often requires life long medica- J Med Genet: first published as 10.1136/jmg.31.8.640 on 1 August 1994. Downloaded from tion with beta blockade. Although linkage to the respective fibrillin genes can be achieved through family studies, diagnosis of sporadic cases of CCA or MS remains clinical and problematical. Other conditions with which CCA can be confused are Stickler syndrome, Achard syndrome, , osteo- genesis imperfecta, and distal . The characteristic clinical manifestations in each of the latter disorders usually allow rapid differentiation.

Aetiology and genetics CCA is an autosomal dominant disorder with variable expressivity within affected kindreds."4 The condition has been described mainly in white families of European extraction, but Japanese,'5 persons of Indian descent,8 African Blacks, 16 and Afro-Americans'7 have also been documented. Shortly after the finding of linkage of Mar- fan syndrome to the fibrillin gene on chromo- some 15ql5-21, Lee et al3 and, later, Tsipour- Figure 3 A young boy with CCA showing pectus as et a15 showed linkage of CCA families to a carinatum (reproduced from Viljoen D, et al, Clin Genet second fibrillin locus on 5q23-31. No intrage- 1991;31:181-8). nic mutations have so far been characterised in fibrillin 5. Nevertheless, Marfan syndrome and CCA have now finally been separated on a molecular basis as two distinct entities. Intra- genic heterogeneity within the fibrillin 5 gene is likely to be responsible for the wide pheno- typic differences in patients with CCA. http://jmg.bmj.com/ Management In view of the normally benign prognosis of patients with CCA, management is usually confined to physiotherapy in early childhood to increase joint mobility and lessen the effects of muscle hypoplasia. Infrequent cardiovascu- lar and ophthalmological appraisal (perhaps on October 1, 2021 by guest. Protected copyright. five yearly) is recommended in all affected persons to exclude the rare development of aortic dilatation, complications associated with Figure 4 Severe mitral valve prolapse, and progressive lens kyphoscoliosis, joint subluxation. Prenatal diagnosis is feasible in contractures, and calf muscle hypoplasia in a boy families that are large enough for linkage stud- with CCA (reproduced ies, but the demand for such investigations is from Beighton P, likely to be small in view of the generally Inherited disorders of the skeleton, 1988:407-8). benign nature of the disorder. The compilation of this manuscript was made possible by aortic root dilatation may represent the severe grants from the South African Medical Research Council, the Mauerberger Fund, the Cooper Lowveld Fund, and the end of the spectrum of CCA, MS, or a new, as University of Cape Town Staff Research Fund. I would also yet undefined, genetic entity. like to thank Kim Wenning for typing the manuscript.

1 Beals RK, Hecht F. Congenital contractural arachnodac- tyly. A heritable disorder of connective tissue. 7 Bonie OPHTHALMOLOGICAL COMPLICATIONS Joint Surg (Am) 1971;53:887-903. As with severe cardiovascular manifestations, 2 Hecht F, Beals RK. "New" syndrome of congenital con- tractural arachnodactyly originally described by Marfan the ophthalmological features of lens subluxa- in 1896. Pediatrics 1972;49:574-9. tion and myopia are also said to differentiate 3 Lee B, Godfrey M, Vitale E, et al. Linkage of Marfan at two syndrome and a phenotypically related disorder to two between MS and CCA. However, least different fibrillin genes. Nature 1991;353:330-4. patients with well documented, severe CCA 4 Kainulainen K, Pulkkinen L, Savolainen A, Kaitila I, have also been with Peltonen L. Location on chromosome 15 of the gene reported ectopia lentis,9 defect causing Marfan syndrome. N Engi _7 Med keratoconus, and myopia.'3 1990;323:935-9. Congenital contractural arachnodactyly (Beals syndrome) 643

5 Tsipouras P, Del Mastro R, Sarfarazi M, et al. Genetic 11 Wainer S. Congenital contractural arachnodactyly in an linkage of the Marfan syndrome, ectopia lentis, and African Negro kindred. S Afr Med (in press). congenital contractural arachnodactyly to the fibrillin 12 Langenskuld A. Congenital contractural arachnodactyly: re- genes on chromosomes 15 and 5. N Engl Med port of a case and of an operation for contracture. 1 992;326:905-9. Bone J3oint Surg 1985;67:44-6. 6 Ramos Arroyo MA, Weaver DD, Beals RK. Congenital 13 Bass HN, Sparkes RS, Crandall BF, Marcy S. Congenital J Med Genet: first published as 10.1136/jmg.31.8.640 on 1 August 1994. Downloaded from contractural arachnodactyly. Report of four additional contractural arachnodactyly, keratoconus and probable families and review of the literature. Clin Genet Marfan syndrome in the same pedigree. Pediatr 1985;27:570-81. 1981;98:591-3. 7 Currarino G, Friedman JM. A severe form of congenital 14 Hall J. Arachnodactyly, contractural Beals type. In: Buyse contractural arachnodactyly in two newborn infants. Am ML, ed. Birth defects encyclopedia. Cambridge, Massachu- Med Genet 1986;25:763-73. setts: Blackwell Scientific Publications, 1990:174-5. 8 Viljoen D, Ramesar R, Behari D. Beals syndrome: clinical 15 Shikata J, Yammamuro T, Mikawa Y, et al. Kyphoscoliosis and molecular investigations in a kindred of Indian des- in congenital contractural arachnodactyly. Spine cent. Clin Genet 1991;39:181-8. 1987;12:1055-8. 9 Bowle E, Quigg MH. Ectopia lentis and aortic root dilation 16 Beighton P. Congenital contractural arachnodactyly. In: in congenital contractural arachnodactyly. Am Med Beighton P, ed. Inherited disorders of the skeleton. Edin- Genet 1992;42:19-21. burgh: Churchill Livingstone, 1988:407-8. 10 Huggon IC, Burke JP, Talbot JF. Contractural arachno- 17 Steg NL. Congenital contractural arachnodactyly in a Black with mitral regurgitation and iridonesis. Arch Dis family. Birth Defects 1975;11:57-62. Child 1990;65:317-19. http://jmg.bmj.com/ on October 1, 2021 by guest. Protected copyright.