A variant of Cenani-Lenz syndactyly (CLS): review of the literature and attempt of classification

British Journal of Plastic Surgery (2005) 58, 251–257

A variant of Cenani-Lenz syndactyly (CLS): review of the literature and attempt of classification C. Harpfa,*, M. Pavelkab, H. Hussla a

University Hospital of Plastic and Reconstructive Surgery and Ludwig Boltzmann Institute for Quality Control in Plastic Surgery, University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, Austria b University Hospital of Clinic Surgery, Clinical Department of Vascular Surgery, University of Innsbruck, Anichstraße 35, A-6020 Innsbruck, Austria Received 18 June 2003; accepted 22 October 2004

KEYWORDS Cenani-Lenzsyndrome—CLS; Syndactyly; Hand malformation

Summary An oligodactylous variant of Cenani-Lenz syndactyly and its surgical treatment is presented. The deformity is believed to be of autosomal recessive inheritance and caused by a disordered axial and longitudinal differentiation of the upper and lower extremities. The classical form is mainly characterised by a complete syndactyly of the hands. Malformations may also affect the bones of the forearm and, to a lesser extent, the lower limbs. We analysed clinical features and compared them with those previously described. According to our research of literature and our clinical findings there seem to exist two grossly different clinical phenotypes: spoon hand type and oligodactyly type. Typical constant clinical features such as carpal, metacarpal and digital synostoses, disorganisation of carpal bones, reduction of digital rays and syndactyly of toes are found in the reported cases. Inconstant features such as radio-ulnar synostosis, brachymesomelia, metatarsal synostoses and reduction of metatarsal rays may be present. In our case, successful bilateral digital ray individualisation and tendon transfers were performed to construct a grip function of the grossly deformed hands. Q 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved.

Since the first case of two siblings was described,1 the Cenani-Lenz syndactyly (CLS)-type of extremity malformation was hitherto defined as complete and complex syndactyly of the hands combined with malformations of the forearm bones and similar manifestations in the lower limbs. * Corresponding author. Address: LKH Feldkirch, Carinagasse 47, 6800 Feldkirch, Austria. Fax: C43 552 2303 7505. E-mail address: [email protected] (C. Harpf).

A few publications associate this rare syndactyly with other more frequent forms of syndactyly. According to Buyse, Cenani Lenz syndactyly belongs to ‘syndactyly type IV’.2 Acrocephalosyndactyly, amniotic bands syndrome, Poland syndrome and syndactylies with multifactorial inheritance are excluded in Buyse’s classification. Tentamy and McKusick classified this type as ‘group 5 of the isolated syndactylies’.3 The classical type of CLS shows a complete

S0007-1226/$ - see front matter Q 2004 The British Association of Plastic Surgeons. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.bjps.2004.10.024

252 cutaneous fusion of the fingers, giving the hands a mitten- or cup-like appearance.1 Certain digital rays may be absent in some cases. Nails mostly are multipartite. Unlike this classical type, the majority of the CLS reported so far do not show the typical spoon-hand but show some individualisation of digital rays.4–13 On each hand there are usually two or three grossly abnormal, short and partly fused rays with nails. A rudimentary thumb or single fan-like digits with nails is seen as in our patient. Clinical features of the cases reported as CLS in literature are listed in Table 1. The carpal bones are fused to a variable extent; the metacarpals also tend to show synostoses, in some cases forming a single bony mass.8 Forearm manifestations are an inconstant feature of CLS (Tables 1 and 2): Radius and ulna may either be fused, reduced in length, or rudimentary. Forearm shortness (mesomelic shortness, brachymesomelia) is severe in some cases,7,8,10,14,18 in other cases it is missing.5,9,11,15 The lower extremities are generally less severely affected: in the majority of cases we can see syndactyly of toes, metatarsal synostoses or a reduction in the number of rays. Manifestations in the tibia or fibula are only reported once in all cited cases.16 Constant and inconstant findings of CLS are listed in Table 2. Associated malformations are rarely reported and may be accidental. Verma presented a patient with a typical oligodactylous CLS with ptosis, nystagmus, and a high-arched palate.12 Renal hypoplasia4 and vertebral anomalies14 are also reported to be rarely associated in single CLS.

Genesis, inheritance Congenital fusion of the limb bones originate in the fifth week of embryonic life due to a disturbed induction of the digital rays.9 Little information is reported concerning the genetic background of CLS: Gene mapping and gene linkage are unknown.2 Reported cases originating from consanguineous unions2,4,6,9 confirm the autosomal recessive inheritance, though De Smet6 assumes gonadal mosaicism due to an autosomal dominant gene.

Surgery Very few cases with successful surgical intervention are reported. The reconstruction of an individualised finger out of the anarchic bone-mass was recommended, but the functional results of

C. Harpf et al. syndactyly release of the first web to construct an opposable digit for minimal pinch function are regarded as unsatisfactory.5 One of the recently published cases13 underwent an unsuccessful bilateral release of the first web.

Case report The 18-month-old boy, who was born following an uneventful pregnancy, is the first child of parents who have no clinical or radiological abnormality of their extremities but are second cousins. The hand and foot anomalies were almost symmetrical. The oligodactylous hands had three grossly deformed and shortened rays with nails (Fig. 1). The metacarpus was represented by two bony masses of which each may be composed of two metacarpals respectively. The radially lying metacarpal block was the smaller one and, on the right hand, more individualised. The two clusters showed a cartilaginous junction on the right hand and an osseous junction in the left hand. A plate of irregularly syndactylous rays was articulated upon the partial syndactylous metacarpals. The innermost ray was more individual and could be the thumb or a fusion between thumb and index finger with two irregular digital bones and a broad irregular nail. The other digits showed a complete osteocutaneous syndactyly. They contained two proximally lying triangular bones similar to a delta phalanx, one central bony mass and three distal phalangeal segments in the right hand and five in the left hand, respectively, with a bipartite nail. Additionally, a hypoplastic triphalangeal digit with a small hypoplastic nail arised from the dorsal ulnar aspect of the metacarpal level (Figs. 1 and 2). The feet were less severely affected: Both feet showed a fusion of metatarsals IV and V. The left foot presented a cutaneous syndactyly of toes II and III and a fibular hexadactyly with a dorsally displaced irregular ray consisting of hypoplastic metatarsal and phalangeal bones. The parents were instructed concerning the genetic risk for possible future children.

Surgical treatment At the age of 19 months the radial ray of the right hand was individualised, comparable to a pollicisation. The ray was divided from the syndactylous plate on metacarpal and digital level, rotated and opposed. Resorbable sutures were used to reattach the carpo-metacarpal junction. There were no intrinsic muscles to reconstruct the thenar muscles.

Comparison of clinical features of the cases reported as CLS in literature Type of CLS

Metacarpal synostosis

Disorganisation of phalanges

Number of digital rays

Radio-ulnar synostosis

Forearm shortening

Hypoplastic rays/toes

Metatarsal synostosis

Syndactyly of toes

Inheritence (suggested)

Con-Sanguinity of parents

Liebenam 1938 (10) Barsky 1958 (17) Yelton (1) 1962 (16) Yelton (2) 1962 (16) Cenani (1) 1967 (1) Cenani(2) 1967 (1) Drohm(1) 1976 (8) Drohm (2) 1976 (8) Drohm (3) 1976 (8) Lenz und Cenani (18) Dodinval (brother) 1979 (7) Dodinval (sister) 1979 (7)

Oligodactyly

C

C

2

K

C

C

C

C

?

?

Oligodactyly Oligodactyly

C C

C C

3 1 (right)

Complete Inclomplete

C C

? C

? K

? C

? ?

?

Oligodactyly

C

C

3

K

C

C

C

C

?

Spoon hand

C

C

0

Inclomplete

?

K

K

C

autos. recessive

K

Spoon hand Spoon hand Oligodactyly

C C C

C C C

0 0 4

Inclomplete Inclomplete Inclomplete

? C C

K C K

K C C

K C C

autos. recessive autos. recessive autos. recessive

K ? ?

Spoon hand

C

C

6C

?

?

C

C

C

?

K

Spoon hand

C

C

0

C

C

C

?

C

autos. recessive

C

Oligodactyly

C

C

3

K

C

C

C

C

autos. recessive

K

Oligodactyly

C

C

2

C

C

C

C

autos. recessive

K

Pfeiffer 1982 (11)

Oligodactyly

C

C

?

K

K

C

autos. recessive

K

Elcioglu 1997 (9)

Oligodactyly

C

C

3 (left) 4 (right) 4

Inclomplete (almost complete) K K

K

K

C

autos. recessive

C

De Smet (father) 1996 (6) De Smet (daughter) 1996 (6) De Smet 1992 (5) Verma 1976 (12)

No CLS

C

K

6

K

K(right)C (left) K

K

C

C

Autos. dominant

K

No CLS

C

K

6

K

K

C

C

C

Autos. dominant

K

Spoon hand Oligodactyly

C C

C C

K complete

K ?

K C

K C

? C

? autos. recessive

K C

Seven 2000 (14) Bacchelli 2001 (4) Nezerati 2002 (13) Present case

Spoon hand Oligodactyly Oligodactyly Oligodactyly

C C C C

C C C C

0 3 (right) 4 (left) 0 1 2 3

complete complete K K

C ? C K

C(left) K C C

C K C C

C C K C(left)

? ? ? autos. recessive

K C K C

A variant of Cenani-Lenz syndactyly (CLS)

Table 1

Abbreviations; ?, Unknown; C, Yes; K, No; Autos, Recessive, Autosomal recessive; Autos; Dominant, Autosomal dominant.

253

254 Table 2

C. Harpf et al. Constant and inconstant clinical features of CLS

Constant features

Inconstant features

Disorganisation of carpal bones Carpal synostoses Metacarpal synostoses Numeric reduction of digital rays (hand) Digital synostoses (hand) Syndactyly of toes

Complete metacarpal block Spoon hand (complete syndactyly) Oligodactyly Radio-ulnar synostosis (proximal-complete) Brachymesomelia Radius head dislocation Metatarsal synostoses Numeric reduction of rays (foot)

The first web was formed by a Z-plasty and skin grafts. We tried to reintegrate the ulno-dorsal ray into the palm by ulnar and palmar transposition of its metacarpal bone and by fixation of its metacarpal head to the neighbouring metacarpal head with non-absorbable sutures. Due to absence of flexor or extensor tendons the individualised radial ray (neopollex) could not be moved actively after the first operation. Therefore the strong extensor tendon of the ulno-dorsal ray was transferred to the neopollex as an extensor/abductor. The first web was shaped with a dorsal advancement flap and a full thickness skin graft. In the fourth operation, one of altogether four palmar tendons found intraoperatively, likely to be digital flexor tendons, was transferred to the neo-pollex to achieve opposition. The flexor tendons lacked any tendon sheet. Furthermore, an unstable ‘interphalangeal’ joint of the neo-pollex was stabilised by titanium-platearthrodesis (Table 3). The left hand was reconstructed in a similar manner: After individualisation of the first ray the ulno-dorsal ray was integrated into the palm. The first web was deepened during the second operation. Unlike the right hand, no flexor tendon could be found. Therefore, the strong extensor tendon of the ulno-dorsal ray was transferred to the palmar side to achieve active flexion. Finally, tenorhaphy of the extensor tendon and tenolysis of the new flexor tendon of the neo-pollex was performed. Besides surgical corrections, a range of physical therapy was commenced. Two years after the last operation the 5 year old boy has acquired satisfying function of both hands (Figs. 3 and 4): abduction and opposition of the thumb and flexion of the other syndactylous rays in metacarpophalangeal level are possible on both hands. Small objects can be grasped actively. According to the tendon transfer to the right thumb the extension/abduction is better on the right than on the left hand (Figs. 5 and 6). By now, no further operations are planned. The interphalangeal joint of the left thumb is stable, and its

ulnar deviation is beneficial for precision grip and will therefore not be operated on.

Discussion Two main different phenotypes of CLS seem to exist: the ‘classic’ Cenani-Lenz type with total syndactyly and synostosis, and the variant with oligodactyly and partial syndactyly (see Table 1). Our patient’s hand does not correspond to the classical cup-like hand described by Cenani in 19671 but is comparable to the hand anomalies described by other authors.7,11,12,17 There is disagreement concerning the nomenclature of the different phenotypes. The various clinical features (total/incomplete syndactyly, oligodactyly, presence or absence of forearm or lower limb manifestations) seem to result in a differentiation between the classic ‘Cenani syndactyly’ and the ‘Cenani-Lenz type of syndactylism’. Both terms are used irregularly in the literature. Nevertheless, similar localisations of bone deformities with varying extent are found among all reported cases. With regard to the variability of the published cases with interfamilial variations and descriptions as ‘atypical split-hand’,12 ‘unusual case of clubhand’6 or ‘oligodactyly’,7 we suggest subdivision and even heterogeneity. There is considerable variation among the CLS-cases, especially in the degree of expression of the clinical signs, whereas within a specific patient hand and foot anomalies are almost always symmetrical except in one case.5 Dodinval7 mentioned the fact that different phenotypes of CLS exist but did not consider them as very fundamental. Pfeiffer11 states that more observations are needed to show whether subdivision due either to isoallelism or heterogeneity is possible or necessary. This may be true from the genetic point of view, but, concerning the hand manifestations, we propose to subdivide the cases into two groups: the classical or spoon-hand type and the oligodactyly-type.

A variant of Cenani-Lenz syndactyly (CLS)

Figure 1 Hand anomalies of the patient at the age of 18 months. (A) Dorsal view, (B) palmar view.

Furthermore, the number of reported cases seems to be more extensive than supposed. To date, 22 cases of CLS have been described to our knowledge. The patient presented by Verma,12 classified as ‘split hand with an autosomal recessive inheritance’, matches clinically with our patient and with other cases of the oligodactyly-type of CLS. Drohm’s case 28, not classified as CLS by the author, corresponds with the oligodactyly-type of CLS, too. Table 3

255

Figure 2 X-ray of both hands of the patient at the age of 18 months. (A) Dorsopalmar, (B) lateroposition.

On the other hand two observations recently presented by De Smet in father and daughter6 seem to be a different entity missing the common features of CLS, mainly the symmetrical anarchistic rearrangement of carpus, metacarpals and phalanges. This clinical appearance with single unilateral metacarpal synostosis, one partial syndactyly and duplication of one phalangeal ray seem to belong to the heterogeneous sequence of cleft hand, central polydactyly and syndactyly.15

List of operations performed in the present case

Age (months)

Surgical treatment (right hand)

19 25

Individualisation of the radial ray, integration of the ulno-dorsal ray Tendontransfer: ulno-dorsal ray (extensor tendon)Oneo-pollex (extensor/ abductor) Deepening of web I (dorsal advancement flapCskin graft) Opponensplasty (a flexor digitorum tendon) Arthrodesis neo-pollex

31 37 49 Surgical treatment (left hand) 46 Individualisation of the radial rayintegration of the ulno-dorsal ray 49 Tendon transfer: extensor tendon (ulno-dorsal ray)Oneo-pollex (flexor tendon) deepening of web I (dorsal advancement flapCskin graft) 55 Tenorhaphy (extensor tendon of neo-pollex), tenolysis (flexor tendon of neo-pollex)

256

Figure 3 Clinical appearance of both hands at the age of 6 years. (A) Dorsal view, (B) palmar view.

Additionally, the apparently autosomal dominant inheritance confirms this assumption. In proportion to the other reported patients these two cases may not be classified as CLS. According to the latter the definition and demarcation of the CLS from typical and atypical split hand seems worth being mentioned. Ogino15 stated that the typical cleft hand is marked by an impairment of the middle finger with a V-shaped cleft in its place. In more severe cases the central three digits are missing, possibly affecting the metacarpal level. Based on the fact that this malformation is entailed on abnormalities of the induction of the central digital rays, it is possible that cleft hand is closely related to central syndactyly or even polydactyly. In spite of some similar or common clinical attributes CLS is a more complex phenomenon affecting not only digits and metacarpus. It is characterised not only by longitudinal but also by transverse disturbance of limb development. Furthermore it is well accepted today that the atypical cleft hand is marked by a dysplasia and shortness of the central digital rays without a V-shaped cleft and without impairment of

C. Harpf et al.

Figure 4 X-ray of the hand at the age of 6 years. (A) Dorsopalmar, (B) lateroposition.

the carpal and metacarpal skeleton. This entity has therefore to be delimitated from CLS. Cenani-Lenz syndactyly is marked by a nonuniform clinical presentation. It is ultimately caused by a disordered axial and longitudinal differentiation of hands and feet. Cases primarily termed as CLS proved to be cases of atypical split

Figure 5 Functional aspect of the hands two years after surgical correction: the patient can grasp small things like buttons or a sheet of paper.

A variant of Cenani-Lenz syndactyly (CLS)

Figure 6 Functional assessment: at the age of 6 years the patient is able to use the right neo-pollex for writing.

hand, when looking at them more closely. The other way an ample number of reported (partially ‘nonclassifiable’) cases, not classified as CLS originally, seem to belong to CLS. After revision of available literature and reported cases, we finally advance a more precise definition of CLS: CLS is a congenital malformation syndrome of probably autosomal recessive inheritance involving both, upper and lower extremity. The principal clinical presentation is marked by a nearly symmetrical presence of a spoon hand (classical type) or, more frequently, an oligodactylous hand. Despite this essential difference the following constant clinical features, of variable extent, are found in all the reported cases: carpal, metacarpal and digital synostoses, disorganisation of carpal bones, numeric reduction of digital rays and syndactyly of toes. Besides, following inconstant features may be present: radio-ulnar synostosis, brachymesomelia, radius head dislocation, metatarsal synostoses and numeric reduction of rays.

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257 2. Buyse ML, editor. Birth defects encyclopedia. In: Center for birth defects information services, vol. I. USA: Dover; 1990. p. 1617–9. 3. Temtamy SA, McKusick VA. In: The genetics of hand malformations. Birth defects: original article series, vol. XIV. New York: AR Liss; 1978. p. 320–2. No. 3. 4. Bacchelli C, Goodman FR, Scambler PJ, Winter RM. CenaniLenz syndrome with renal hypoplasia is not linked to FORMIN or GREMLIN. Clin Genet 2001;59:203–5. 5. De Smet L, Winnepenninckx B, Fryns JP, Fabry G. CenaniLenz type of syndactyly: a complex type of syndactyly with multiple synostoses. Genet Couns 1992;3:145–7. 6. De Smet L, De Beer P, Fryns JP. Cenani-Lenz syndrome in father and daughter. Genet Couns 1996;7:153–7. 7. Dodinval P. Oligodactyly and multiple synostoses of the extremities: two cases in sibs. A variant of Cenani-Lenz syndactyly. Human Genet 1979;48:183–9. 8. Drohm D, Lenz W, Yang TS. Totale Syndaktylie mit mesomeler Armverku ¨rzung, radioulnaren und metacarpalen Synostosen und Disorganisation der Phalangen (‘CenaniSyndaktylie’). Klinische Paediatrie 1976;188:359–65. 9. Elc ¸ioglu N, Atasu M, Cenani A. Dermatoglyphics in patients with Cenani-Lenz type syndactyly: studies in a new case. Am J Med Genet 1997;70:341–5. ¨ ber gleichzeitiges Vorkommen von Glied10. Liebenam L. U mabendefekten und osteosklerotischer Sytemerkrankung ¨r menschliche Vererbungs und KonstitutionZeitschrift fu slehre 1938;21:697–703 11. Pfeiffer RA, Meisel-Stosiek M. Present nosology of the Cenani-Lenz type of syndactyly. Clin Genet 1982;21:74–9. 12. Verma IC, Joseph R, Bhargava S, Mehta S. Split-hand and split-foot deformity inherited as an autosomal recessive trait. Clin Genet 1976;9:8–14. 13. Nezarati MM, McLeod DR. Cenani-Lenz syndrome: report of a new case and review of the literature. Clin Dysmorphol 2002;11:215–8. 14. Seven M, Yuksel A, Ozkilic A, Elc ¸ioglu N. A variant of CenaniLenz type syndactyly. Genet Couns 2000;11:41–7. 15. Ogino T. Congenital anomalies of the hand. An Asian perspective. Clin Orthop 1996;323:12–21. 16. Yelton CL. Certain congenital limb deficiencies occurring in twins and half-siblings. Inter-Clin Inf Bull 1962;1:1–7. 17. Barsky AJ. Congenital anomalies of the hand and their surgical treatment. In: Goff CW, editor. Publication number 311, American lecture series, a monograph in the bannerstone division of American lectures in orthopedic surgery. Illinois, USA: Charles C. Thomas, Springfield; 1958. p. 135. 18. Lenz W, Cenani A. Total syndactyly. The fifth conference on the clinical delineation of birth defects. Baltimore 1972. Cited in: Drohm D, Lenz W, Yang TS. Totale Syndaktylie mit mesomeler Armverku ¨rzung, radioulnaren und metacarpalen Synostosen und Disorganisation der Phalangen (‘CenaniSyndaktylie’). Klinische Paediatrie 1976;188:359–65.