- Email: [email protected]
Congenital hand anomalies in Japan: A family study
Congenital hand anomalies in Japan: A family study During the 20-year period from 1968 to 1987, 1024 patients with congenital anomalies of the hand from 1000 Japanese families were examined in our clinic. Of these patients, 204 had relatives with limb anomalies. While postaxial polydactyly showed a 33% level of familial recurrence, symphalangism and Kirner’s syndrome showed about 23% recurrence, syndactyly 18%, radiouinar synostosis 9%, radial ray deficiency 8%, cleft hand 7%) and duplicated thumb 5%. None of the relatives had ulnar deficiency or symbrachydactyly. (J HAND SIJRG 1990;15A:43944.)
T. Miura, MD, R. Nakamura,
MD, and E. Horii, MD, Nagoya, Japan
The incidence of the causes of congenital anomalies is still unknown.’ For people who have congenital anomalies, the penetrance ratio to their descendants is of great concern. However, few reports offer data on family recurrence in large numbers of groups.‘* 3 Materials and methods
A study was made of congenital anomalies of the upper limb in the families of affected patients registered in our clinic from 1968 to 1987. The family study of each patient involved the evaluation of siblings, parents, grandparents, great-grandparents, uncles, aunts, and cousins. Nearly all living siblings and parents were examined. Information about other relatives was obtained from the parents of the index patients. In patients registered in our clinic, 204 had relatives who also had limb anomalies. Eighty-eight index patients with minor anomalies such as brachy-phalangia and brachymetacarpa, dinodactyly, clasped thumb, and camptodactyly were excluded from this study. The remaining 116 patients from 92 families were classified by the phenotypes of proband into the following 12 groups. Three From the Department Nagoya University,
of Orthopedic Surgery, Nagoya, Japan.
Received for publication July 18, 1989.
School of Medicine,
May 16, 1989; accepted
in revised form
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint request: Takayuki Miura, MD, Department of Orthopedic Surgery, Nagoya University, 65 Tsuruma-cho, Showa-lcu, Nagoya, 466, Japan. 3/l/15912
patients with Ellis-van Creveld syndrome were excluded. Results
Results of the study showed the following: 1. Phenotype of proband: Polydactyly A. Duplicated thumb In our study, duplicated thumb was found in 379 patients. Twenty-one of these patients (representing 17 out of 375 families, 4.6%) had relatives exhibiting some congenital limb anomaly. In 13 families, the anomaly of proband was a simple duplicated thumb; simple duplicated thumb was found in seven families (one sibling of three families, the father of one, the mother and one maternal aunt of one, the paternal grandmother of one, and one paternal uncle of one); polydactyly of the feet in two (one paternal uncle of one family and one maternal cousin of one); duplicated thumb and webbing between the second and third toes in one brother; five-fingered hand in one paternal cousin; stub thumb (brachyphalangia of the thumb) in one father; and webbing of the feet in one great-grandfather. In the other four families, anomalies of proband were duplicated thumb with additional limb anomalies such as webbing of the toes, polysyndactyly of toes, and triphalangeal thumb, duplicated thumb ;was found in two families (the paternal grandmother of one family, and the father and the paternal grandfather of one); cleft lip and duplicated thumb
THEJOURNAL OFHANDSURGERY439
440
The Journal of HAND SURGERY
Miura, Nakamura, and Horii
Table I. Congenital
limb anomalies
in a family with duplicated
thumb
Total number of families
Phenotype of proband
Phenotype of relatives
Number of families
Number of patients
375 Families
Duplicated thumb ( 13 Families)
Duplicated thumb Polydactyly of feet Duplicated thumb and webbing of toes Five-fingered hand Stub thumb Webbing of toes Duplicated thumb Stub thumb
7 2 1
15 4 2
1 1 1 1 1
2 2 2 2 4
Duplicated thumb and cleft lip Duplicated thumb
1
2
1
3
Duplicated thumb and webbing of toes (2 Families) Duplicated thumb and polydactyly of toes Duplicated thumb and triphalangeal thumb
Table II. Congenital polydactyly
limb anomalies in a family with postaxial polydactyly, postaxial and preaxial and synpolydactyly (three families with Ellis-van Creveld syndrome are excluded)
Total number of families 9 Families 24 Families
Phenotype of proband
Phenotype of relatives
Number of families
Number of patients
Postaxial polydactyly
Postaxial polydactyly
3
7
Postaxial and preaxial polydactyly (7 Families) Synpolydactyly
Similar anomalies Webbing of toes Similiar anomalies
6 1 1
24 2 2
in one brother; and stub thumb in the mother, one maternal aunt, and the grandmother (Table I). B. Postaxial polydactyly Five out of 11 patients (representing 3 out of 9 families, 33%) had relatives with postaxial polydactyly. In all three families, postaxial polydactyly was found in siblings only, and the type of polydactyly was the same as that of the proband. Three patients with the Ellis-van Creveld syndrome (recessive inheritance) were excluded from this data (Table II). C. Postaxial and preaxial polydactyly and synpolydactyly Nine out of 25 patients (representing 8 out of 24 familes, 33%) with postaxial and preaxial polydactyly or synpolydactyly had relatives who also had limb anomalies. In six of the eight families, congenital anomalies the same as the proband were found in one of the parents and other relatives. This is compatible with autosomal dominant inheritance. In another two families, congenital limb
anomalies were found only in siblings. The phenotype of one sister was the same as that of the proband. However, another sister had a simple webbing between the second and third toes (Table II). II. Phenotype of proband: Syndactyly A. Syndactyly involving the ring and small fingers Nine out of 25 patients (representing 7 out of 23 families, 30%) with syndactyly between the ring and small fingers had relatives with limb anomalies. Members of six out of seven families (the father, the paternal grandfather, and great-grandfather of one family, the mother of one, the paternal grandmother of one, the maternal great-grandmother of one, one maternal uncle of one, and one sister of one) showed syndactyly like that of the proband. In three families, clinodactyly with brachymesophalangia of the small finger was found (Table III). B. Syndactyly not involving the small finger Eleven out of 67 patients (representing 9 out of 65 families, 14%) with syndactyly be-
Vol. 15A, No. 3 May 1990
Table III. Congenital Total number of families 23 Families
65 Families
60 Families
Table IV. Congenital
Congenital
limb anomalies
in a family with syndactyly
Phenotype of proband
hand anomalies
in Japan
441
and typical cleft hand Number of Families
Number of patients
Webbing of fingers Webbing of fingers and clinodactyly (small) Clinodactyly (small)
4 2
10 6
1
3
Webbing of long and ring fingers (9 Families)
Webbing of fingers Webbing of fingers; polydactyly of feet
5 1
12 4
Typical cleft hand (4 Families)
Clinodactyly (small) Cleft hand Cleft hand Webbing of fingers
2 1 2 2
9 2 4 7
Webbing of fingers (including small finger) (7 Families)
limb anomalies
Phenotype of relatives
in a family with ray deficiency Phenotype of relatives
and radioulnar
Total number of families
Phenotype of proband
85 Families
Absence of radius Hypoplastic thumb (4 Families) Five-fingered hand
Similiar anomalies Similiar anomalies Clasped thumb Triphalangeal thumb Five-fingered hand
12 Families
Ulnar ray deficiency Radioulnar synostosis (2 Families)
No relatives with limb anomalies Radioulnar synostosis Anomalies of the toes (Phenotype unknown) Brachyphalanges
Radioulnar synostosis and brachyphalanges Radioulnar synostosis and absence of thumb Humeroulnar synostosis
synostosis
Number of families
Number of patients
1 1
2 2
1
2
Similiar anomalies
1
2
Similiar anomalies
1
2
tween the long and ring fingers (including one patient with webbing between the index, long, and ring fingers) had relatives with limb anomalies. Congenital limb anomalies were found only in the siblings of two families, and in one of the parents of three families. In five families (two brothers of one family, the father of one, one maternal uncle of one, one maternal aunt of one, and one paternal cousin of one) out of nine, syndactyly was the same as that of the proband. While syndactyly of the hand with polydactyly or syndactyly of the toes was found in one family (the mother, two maternal aunts, and the
maternal grandmother of one), clinodactyly with brachymesophalangia of the small finger occurred in two families (the father, one paternal uncle, the paternal grandfather, and one brother of one family, and the mother, one maternal aunt and the maternal grandmother of one), and a cleft hand was in the sister of one family. In one of them, the phenotypes of three brothers were not the usual type of syndactyly. They showed shortening of the middle phalanges (brachymesopha langia) not only in the small and index fingers, but also in the long and ring fingers (Table III).
442
The Journal of HAND SURGERY
Miura, Nakamura, and Horii
Table V. Congenital limb anomalies constriction band syndrome
in a family with symbrachydactyly,
1 (cousin)
2
Clasped thumb
1
2
Duplicated thumb Constriction band syndrome
1 1
2 2
Phenotype of relatives
56 Families
Symbrachydactyly
No relatives with limb anomalies
88 Families
So called transverse failure of formation Atypical cleft hand and clasped thumb Constriction band syndrome (2 Families [cousin])
Duplicated
Total number of families 44 Families 21 Families
limb anomalies
and
Number of patients
Phenotype of proband
Table VI. Congenital
failure,
Number of families
Total number of families
72 Families
so called transverse
thumb
in a family with symphalangy
Phenotype of proband Symphalangism (include contracture of IPJ) (11 Families) Kimer’s deformity (5 Families)
III. Phenotype of proband: Cleft hand Six out of 62 patients (representing 4 out of 60 families, 6.7%) with a cleft hand had relatives with limb anomalies. A cleft hand just like of the proband was found in one of the parents in two families. In two other families, webbing between the long and ring fingers was found in siblings, as well as webbing of toes and cleft feet in other relatives (Table III). IV. Phenotype of proband: Radial ray deficiency Eleven out of 89 patients (representing 7 out of 85 families, 8.0%) with radial ray deficiency had relatives with congenital limb anomalies. ’ Absence of the radius was found in siblings of one family. The phenotype of the two siblings was similar, but it was associated with cleft palate and talipes valgus. The phenotype of proband representing four families was a hypoplastic thumb. Congenital limb anomalies were found in the siblings of two of the families (one triphalangeal thumb, and one clasped thumb), and in the mother of the other two families (hypoplastic thumb). In two families, the phenotype of the proband was the five-fingered hand. This same anomaly was found in the father of one family and in the paternal grandfather of the other (Table IV). V. Phenotype of proband: Ulnar deficiency There were no relatives with congenital limb
and Kimer’s
Phenotype of relatives Symphalangism Radioulnar synostosis Kimer’s deformity Unknown shortening of fingers
deformity
Number of families
Number of patients
10 1 4 1
37 2 19 2
anomalies among the 12 patients with congenital ulnar deficiency. VI. Phenotype of proband: Radioulnar synostosis (including synostosis of the humeroulnar joint) Six out of 58 patients (representing 5 out of 57 families, 8.8%) with radioulnar synostosis had relatives with congenital limb anomalies. In two out of five families, the phenotype of the proband was only radioulnar synostosis. In one of them a brother showed the same anomaly as that of proband, and in another family, a paternal cousin had congenital absence of the toes. In one family, the phenotype of the proband was radioulnar synostosis associated with cleft lip and palate, and brachyphalanges (brachyterephalangia, 1 and brachymesophalangia 2,5); the mother of the proband showed only shortening of the phalanges. In another family, radioulnar synostosis was accompanied by the absence of the thumb in the right hand, with a partial absence of the humerus in the left arm, a similar anomaly was found in one sister. In a case of congenital synostosis of the humeroulnar joint, one paternal cousin had an anomaly the same as that of the proband (Table IV). VII. Phenotype of proband: Symbrachydactyly There were no relatives with congenital limb anomalies among 56 patients with symbrachydactyly.
Vol. 15A, No. 3 May 1990
Table VII. Congenital Total number of families 5 6 5 2
Families Families Families Families
12 Families 3 Families 10 Families
Congenital hand anomalies in Japan
limb anomalies
443
in a family with other deformities
Phenotype of proband
Phenotype of relatives
Marfan’s syndrome Madelung’s deformity Ektopic nail Cross union between FPL and FDP Absence of nail Anomaly of FPL Extension contracture of the MP joint
Marfan’s syndrome Madelung’s deformity Ectopic nail Cross union between FPL and FDP
2 1 2 1
6 2 4 2
Absence of nail Hypoplastic thumb Extension contracture of the MP joint
1 1 1
2 2 2
VIII.
Phenotype of proband: Transverse failure of formation (include atypical cleft hand) Only two patients among 88 patients (representing 2 out of 88 families, 2.3%) with transverse failure of formation had relatives with limb anomalies. In one family the maternal cousin had a duplicated thumb. In another family, the proband exhibited congenital clasped thumb in the right hand and an atypical cleft hand in the left; his elder brother showed congenital clasped thumb. The occurrence of duplicated thumb may be coincidental (Table V). IX. Phenotype of proband: Congenital constriction band syndrome Three out of 73 patients (representing 2 out of 72 families, 2.7%) with constriction band syndrome had relatives with congenital limb anomalies. In one family the duplicated thumb was found in one paternal cousin, and in another, the constriction band syndrome was found in one paternal cousin. In these cases, the anomalies were found in rather distant relatives, and no anomalies were found in close relatives (Table V). X. Phenotype of proband: Symphalangism Twelve out of 45 patients (representing 11 out of 44 families, 23%) with symphalangism had relatives with congenital limb anomalies. In all but one of the families, symphalangism the same as that of the proband was found in one of the parents and other relatives. It was compatible with autosomal dominant inheritance. In one family, the phenotype of the proband was an extension contracture of the proximal interphalangeal (PIP) joint of the small finger; one of the relatives showed a radioulnar synostosis (Table VI). XI. Phenotype of proband: Kimer’s deformity Five out of 21 patients (representing 5 out of 21 families, 24%) with Kimer’s deformity had
XII.
Number of families
Number of patients
relatives with congenital limb anomalies. In four out of five families, a similar deformity was found. In three out of four families, the same type of deformity was found in one of the parents and other relatives, while in another family, it was found in the sibling and the maternal grandfather. In another family, shortening of the ring and small finger was found in the grandmother (Table VI). Others In a small number of the patients with other congenital hand anomalies the same anomaly was found in relatives. Four out of seven patients (representing two out of five families) with Marfan’s syndrome had relatives with the same anomaly (mother and one sibling in two families). Two (mother and son) out of seven patients (representing one out of six families) had Madelung’s deformity. Three out of six patients (representing two out of five families) with an ectopic nail had relatives with a similar anomaly (one sibling in two families).“ In one out of two patients with a cross union between the flexor pollicis longus and the index flexor profundus, the father had a similar anomaly. In 1 out of 12 patients with congenital absence of the index fingernail the mother had a similar anomaly. In one out of three patients with an unusual bifurcation of the flexor pollicis longus, the father had a hypoplastic thumb.’ In one out of 10 patients with an extension contracture of the metacarpophalangeal joint, the mother had a similar anomaly (Table VII).
Discussion The fact that webbing of the toes was found in families where the proband exhibited a duplicated thumb suggests that the duplicated thumb may be closely con-
444
Miura, Nakamura, and Horii
netted with the webbing of the toes in the critical period of development and pathogenesis of the fetus. ‘36 The phenotypes of relatives with the postaxial and preaxial polydactyly or synpolydactyly were the same as that of the proband. In addition, the same anomalies were found in close relatives. We also believe that these types of congenital anomalies have strong hereditary characteristics as others have described.7-9 The fact that the webbing of fingers appears to be strongly related to shortening of the middle phalanges and cleft hand, suggests that these anomalies may be closely related to each other.‘, ‘O-M In our study, the overall recurrence ratio of radial or ulnar ray deficiency was low. However, the phenotype of relatives was very similar to that of the proband in these cases. We think that some implicating factor may exist in the formation of this type of anomaly as previously described.3. ‘5-‘7 In families with the so-called transverse failure of formation, only two families showed limb anomalies among the relatives. In addition, the phenotypes of these relatives were different from that of the proband. One had a duplicated thumb and another had a clasped thumb. This suggests that environmental factors may be more important than genetic ones in the pathogenesis of this type of congenital anomaly.“, ‘* REFERENCES Miura T. A clinical study of congenital anomalies of the hand. The Hand 1981;13:59-69. Czeizel A, Maria Bod, Lenz W. Family study of congenital limb reduction abnormalities in Hungary 1975 1977. Hum Genet 1983;65:35-45. Kelikian H . Congenital deformities of the hand and forearm. Philadelphia: WB Saunders, 1974.
The Journal of HAND SURGERY
4. Miura T. Two families with congenital nail anomalies: nail formation in ectopic areas. J HAND SURG 1978;3:348-51. 5. Miura T. Congenital anomaly of the thumb-unusual bifurcation of the flexor pollicis longus and unusual insertion. J HAND SURG 1981;6A:613-5. 1980; 6. Miura T. Polydactyly in Japan. Handchirurgie 12:39-46. 7. Nicolai J-PA. A family with complex bilateral polysyndactyly. J HAND SURG 1988;13A:417-9. 8. Ofodiele FA: Synpolydactyly in three generation of a Nigerian family. East Afr Med J 1982;59:835-9. 9. Rgemorter NV, Milaire J, Haumont RD, Rodesch F. Familial ectrodactyly and polydactyly: variable expressivity of one single gene-embryological considerations. Clin Genet 1982;22:206-10. 10. Manske PR. Cleft hand and central polydactyly in identical twins: a case report. J HAND SURG 1983;8:906-8. 11. Miura T. Syndactyly and split hand. The Hand 1976; 8:125-30. 12. Miura T. Clinical difference between typical and atypical cleft hand. J HAND SURC 1984;9B:31 l-15. 13. Ogino T. A clinical and experimental study on teratogenic mechanism of cleft hand, polydactyly and syndactyly. J Jpn Orthop Assoc 1979;53:585-43. 14. Watari S , Tsuge K. A classification of cleft hands, based on clinical findings. Plast Reconstr Surg 1979;64:381-9. 15. Chiba A, Miura T. A family with hypotrichosis associated with congenital hypoplasia of the thumb. Jap J Human Genet 1979;24:111-17. 16. Holt M, Oram S. Familial heart disease with skeletal malformations. Br Heart J 1960;22:236-42. 17. Miura T. Congenital familial hypoplastic thumb associated with congenital amputation of the toe. J HAND SURG 1984;9A:420-2. 18. Ogino T, Ishii S, Shiono H. Transverse deficiency of the hand in one of monozygotic twins. The Hand 1981;13:7780.
T. Miura, MD, R. Nakamura,
MD, and E. Horii, MD, Nagoya, Japan
The incidence of the causes of congenital anomalies is still unknown.’ For people who have congenital anomalies, the penetrance ratio to their descendants is of great concern. However, few reports offer data on family recurrence in large numbers of groups.‘* 3 Materials and methods
A study was made of congenital anomalies of the upper limb in the families of affected patients registered in our clinic from 1968 to 1987. The family study of each patient involved the evaluation of siblings, parents, grandparents, great-grandparents, uncles, aunts, and cousins. Nearly all living siblings and parents were examined. Information about other relatives was obtained from the parents of the index patients. In patients registered in our clinic, 204 had relatives who also had limb anomalies. Eighty-eight index patients with minor anomalies such as brachy-phalangia and brachymetacarpa, dinodactyly, clasped thumb, and camptodactyly were excluded from this study. The remaining 116 patients from 92 families were classified by the phenotypes of proband into the following 12 groups. Three From the Department Nagoya University,
of Orthopedic Surgery, Nagoya, Japan.
Received for publication July 18, 1989.
School of Medicine,
May 16, 1989; accepted
in revised form
No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article. Reprint request: Takayuki Miura, MD, Department of Orthopedic Surgery, Nagoya University, 65 Tsuruma-cho, Showa-lcu, Nagoya, 466, Japan. 3/l/15912
patients with Ellis-van Creveld syndrome were excluded. Results
Results of the study showed the following: 1. Phenotype of proband: Polydactyly A. Duplicated thumb In our study, duplicated thumb was found in 379 patients. Twenty-one of these patients (representing 17 out of 375 families, 4.6%) had relatives exhibiting some congenital limb anomaly. In 13 families, the anomaly of proband was a simple duplicated thumb; simple duplicated thumb was found in seven families (one sibling of three families, the father of one, the mother and one maternal aunt of one, the paternal grandmother of one, and one paternal uncle of one); polydactyly of the feet in two (one paternal uncle of one family and one maternal cousin of one); duplicated thumb and webbing between the second and third toes in one brother; five-fingered hand in one paternal cousin; stub thumb (brachyphalangia of the thumb) in one father; and webbing of the feet in one great-grandfather. In the other four families, anomalies of proband were duplicated thumb with additional limb anomalies such as webbing of the toes, polysyndactyly of toes, and triphalangeal thumb, duplicated thumb ;was found in two families (the paternal grandmother of one family, and the father and the paternal grandfather of one); cleft lip and duplicated thumb
THEJOURNAL OFHANDSURGERY439
440
The Journal of HAND SURGERY
Miura, Nakamura, and Horii
Table I. Congenital
limb anomalies
in a family with duplicated
thumb
Total number of families
Phenotype of proband
Phenotype of relatives
Number of families
Number of patients
375 Families
Duplicated thumb ( 13 Families)
Duplicated thumb Polydactyly of feet Duplicated thumb and webbing of toes Five-fingered hand Stub thumb Webbing of toes Duplicated thumb Stub thumb
7 2 1
15 4 2
1 1 1 1 1
2 2 2 2 4
Duplicated thumb and cleft lip Duplicated thumb
1
2
1
3
Duplicated thumb and webbing of toes (2 Families) Duplicated thumb and polydactyly of toes Duplicated thumb and triphalangeal thumb
Table II. Congenital polydactyly
limb anomalies in a family with postaxial polydactyly, postaxial and preaxial and synpolydactyly (three families with Ellis-van Creveld syndrome are excluded)
Total number of families 9 Families 24 Families
Phenotype of proband
Phenotype of relatives
Number of families
Number of patients
Postaxial polydactyly
Postaxial polydactyly
3
7
Postaxial and preaxial polydactyly (7 Families) Synpolydactyly
Similar anomalies Webbing of toes Similiar anomalies
6 1 1
24 2 2
in one brother; and stub thumb in the mother, one maternal aunt, and the grandmother (Table I). B. Postaxial polydactyly Five out of 11 patients (representing 3 out of 9 families, 33%) had relatives with postaxial polydactyly. In all three families, postaxial polydactyly was found in siblings only, and the type of polydactyly was the same as that of the proband. Three patients with the Ellis-van Creveld syndrome (recessive inheritance) were excluded from this data (Table II). C. Postaxial and preaxial polydactyly and synpolydactyly Nine out of 25 patients (representing 8 out of 24 familes, 33%) with postaxial and preaxial polydactyly or synpolydactyly had relatives who also had limb anomalies. In six of the eight families, congenital anomalies the same as the proband were found in one of the parents and other relatives. This is compatible with autosomal dominant inheritance. In another two families, congenital limb
anomalies were found only in siblings. The phenotype of one sister was the same as that of the proband. However, another sister had a simple webbing between the second and third toes (Table II). II. Phenotype of proband: Syndactyly A. Syndactyly involving the ring and small fingers Nine out of 25 patients (representing 7 out of 23 families, 30%) with syndactyly between the ring and small fingers had relatives with limb anomalies. Members of six out of seven families (the father, the paternal grandfather, and great-grandfather of one family, the mother of one, the paternal grandmother of one, the maternal great-grandmother of one, one maternal uncle of one, and one sister of one) showed syndactyly like that of the proband. In three families, clinodactyly with brachymesophalangia of the small finger was found (Table III). B. Syndactyly not involving the small finger Eleven out of 67 patients (representing 9 out of 65 families, 14%) with syndactyly be-
Vol. 15A, No. 3 May 1990
Table III. Congenital Total number of families 23 Families
65 Families
60 Families
Table IV. Congenital
Congenital
limb anomalies
in a family with syndactyly
Phenotype of proband
hand anomalies
in Japan
441
and typical cleft hand Number of Families
Number of patients
Webbing of fingers Webbing of fingers and clinodactyly (small) Clinodactyly (small)
4 2
10 6
1
3
Webbing of long and ring fingers (9 Families)
Webbing of fingers Webbing of fingers; polydactyly of feet
5 1
12 4
Typical cleft hand (4 Families)
Clinodactyly (small) Cleft hand Cleft hand Webbing of fingers
2 1 2 2
9 2 4 7
Webbing of fingers (including small finger) (7 Families)
limb anomalies
Phenotype of relatives
in a family with ray deficiency Phenotype of relatives
and radioulnar
Total number of families
Phenotype of proband
85 Families
Absence of radius Hypoplastic thumb (4 Families) Five-fingered hand
Similiar anomalies Similiar anomalies Clasped thumb Triphalangeal thumb Five-fingered hand
12 Families
Ulnar ray deficiency Radioulnar synostosis (2 Families)
No relatives with limb anomalies Radioulnar synostosis Anomalies of the toes (Phenotype unknown) Brachyphalanges
Radioulnar synostosis and brachyphalanges Radioulnar synostosis and absence of thumb Humeroulnar synostosis
synostosis
Number of families
Number of patients
1 1
2 2
1
2
Similiar anomalies
1
2
Similiar anomalies
1
2
tween the long and ring fingers (including one patient with webbing between the index, long, and ring fingers) had relatives with limb anomalies. Congenital limb anomalies were found only in the siblings of two families, and in one of the parents of three families. In five families (two brothers of one family, the father of one, one maternal uncle of one, one maternal aunt of one, and one paternal cousin of one) out of nine, syndactyly was the same as that of the proband. While syndactyly of the hand with polydactyly or syndactyly of the toes was found in one family (the mother, two maternal aunts, and the
maternal grandmother of one), clinodactyly with brachymesophalangia of the small finger occurred in two families (the father, one paternal uncle, the paternal grandfather, and one brother of one family, and the mother, one maternal aunt and the maternal grandmother of one), and a cleft hand was in the sister of one family. In one of them, the phenotypes of three brothers were not the usual type of syndactyly. They showed shortening of the middle phalanges (brachymesopha langia) not only in the small and index fingers, but also in the long and ring fingers (Table III).
442
The Journal of HAND SURGERY
Miura, Nakamura, and Horii
Table V. Congenital limb anomalies constriction band syndrome
in a family with symbrachydactyly,
1 (cousin)
2
Clasped thumb
1
2
Duplicated thumb Constriction band syndrome
1 1
2 2
Phenotype of relatives
56 Families
Symbrachydactyly
No relatives with limb anomalies
88 Families
So called transverse failure of formation Atypical cleft hand and clasped thumb Constriction band syndrome (2 Families [cousin])
Duplicated
Total number of families 44 Families 21 Families
limb anomalies
and
Number of patients
Phenotype of proband
Table VI. Congenital
failure,
Number of families
Total number of families
72 Families
so called transverse
thumb
in a family with symphalangy
Phenotype of proband Symphalangism (include contracture of IPJ) (11 Families) Kimer’s deformity (5 Families)
III. Phenotype of proband: Cleft hand Six out of 62 patients (representing 4 out of 60 families, 6.7%) with a cleft hand had relatives with limb anomalies. A cleft hand just like of the proband was found in one of the parents in two families. In two other families, webbing between the long and ring fingers was found in siblings, as well as webbing of toes and cleft feet in other relatives (Table III). IV. Phenotype of proband: Radial ray deficiency Eleven out of 89 patients (representing 7 out of 85 families, 8.0%) with radial ray deficiency had relatives with congenital limb anomalies. ’ Absence of the radius was found in siblings of one family. The phenotype of the two siblings was similar, but it was associated with cleft palate and talipes valgus. The phenotype of proband representing four families was a hypoplastic thumb. Congenital limb anomalies were found in the siblings of two of the families (one triphalangeal thumb, and one clasped thumb), and in the mother of the other two families (hypoplastic thumb). In two families, the phenotype of the proband was the five-fingered hand. This same anomaly was found in the father of one family and in the paternal grandfather of the other (Table IV). V. Phenotype of proband: Ulnar deficiency There were no relatives with congenital limb
and Kimer’s
Phenotype of relatives Symphalangism Radioulnar synostosis Kimer’s deformity Unknown shortening of fingers
deformity
Number of families
Number of patients
10 1 4 1
37 2 19 2
anomalies among the 12 patients with congenital ulnar deficiency. VI. Phenotype of proband: Radioulnar synostosis (including synostosis of the humeroulnar joint) Six out of 58 patients (representing 5 out of 57 families, 8.8%) with radioulnar synostosis had relatives with congenital limb anomalies. In two out of five families, the phenotype of the proband was only radioulnar synostosis. In one of them a brother showed the same anomaly as that of proband, and in another family, a paternal cousin had congenital absence of the toes. In one family, the phenotype of the proband was radioulnar synostosis associated with cleft lip and palate, and brachyphalanges (brachyterephalangia, 1 and brachymesophalangia 2,5); the mother of the proband showed only shortening of the phalanges. In another family, radioulnar synostosis was accompanied by the absence of the thumb in the right hand, with a partial absence of the humerus in the left arm, a similar anomaly was found in one sister. In a case of congenital synostosis of the humeroulnar joint, one paternal cousin had an anomaly the same as that of the proband (Table IV). VII. Phenotype of proband: Symbrachydactyly There were no relatives with congenital limb anomalies among 56 patients with symbrachydactyly.
Vol. 15A, No. 3 May 1990
Table VII. Congenital Total number of families 5 6 5 2
Families Families Families Families
12 Families 3 Families 10 Families
Congenital hand anomalies in Japan
limb anomalies
443
in a family with other deformities
Phenotype of proband
Phenotype of relatives
Marfan’s syndrome Madelung’s deformity Ektopic nail Cross union between FPL and FDP Absence of nail Anomaly of FPL Extension contracture of the MP joint
Marfan’s syndrome Madelung’s deformity Ectopic nail Cross union between FPL and FDP
2 1 2 1
6 2 4 2
Absence of nail Hypoplastic thumb Extension contracture of the MP joint
1 1 1
2 2 2
VIII.
Phenotype of proband: Transverse failure of formation (include atypical cleft hand) Only two patients among 88 patients (representing 2 out of 88 families, 2.3%) with transverse failure of formation had relatives with limb anomalies. In one family the maternal cousin had a duplicated thumb. In another family, the proband exhibited congenital clasped thumb in the right hand and an atypical cleft hand in the left; his elder brother showed congenital clasped thumb. The occurrence of duplicated thumb may be coincidental (Table V). IX. Phenotype of proband: Congenital constriction band syndrome Three out of 73 patients (representing 2 out of 72 families, 2.7%) with constriction band syndrome had relatives with congenital limb anomalies. In one family the duplicated thumb was found in one paternal cousin, and in another, the constriction band syndrome was found in one paternal cousin. In these cases, the anomalies were found in rather distant relatives, and no anomalies were found in close relatives (Table V). X. Phenotype of proband: Symphalangism Twelve out of 45 patients (representing 11 out of 44 families, 23%) with symphalangism had relatives with congenital limb anomalies. In all but one of the families, symphalangism the same as that of the proband was found in one of the parents and other relatives. It was compatible with autosomal dominant inheritance. In one family, the phenotype of the proband was an extension contracture of the proximal interphalangeal (PIP) joint of the small finger; one of the relatives showed a radioulnar synostosis (Table VI). XI. Phenotype of proband: Kimer’s deformity Five out of 21 patients (representing 5 out of 21 families, 24%) with Kimer’s deformity had
XII.
Number of families
Number of patients
relatives with congenital limb anomalies. In four out of five families, a similar deformity was found. In three out of four families, the same type of deformity was found in one of the parents and other relatives, while in another family, it was found in the sibling and the maternal grandfather. In another family, shortening of the ring and small finger was found in the grandmother (Table VI). Others In a small number of the patients with other congenital hand anomalies the same anomaly was found in relatives. Four out of seven patients (representing two out of five families) with Marfan’s syndrome had relatives with the same anomaly (mother and one sibling in two families). Two (mother and son) out of seven patients (representing one out of six families) had Madelung’s deformity. Three out of six patients (representing two out of five families) with an ectopic nail had relatives with a similar anomaly (one sibling in two families).“ In one out of two patients with a cross union between the flexor pollicis longus and the index flexor profundus, the father had a similar anomaly. In 1 out of 12 patients with congenital absence of the index fingernail the mother had a similar anomaly. In one out of three patients with an unusual bifurcation of the flexor pollicis longus, the father had a hypoplastic thumb.’ In one out of 10 patients with an extension contracture of the metacarpophalangeal joint, the mother had a similar anomaly (Table VII).
Discussion The fact that webbing of the toes was found in families where the proband exhibited a duplicated thumb suggests that the duplicated thumb may be closely con-
444
Miura, Nakamura, and Horii
netted with the webbing of the toes in the critical period of development and pathogenesis of the fetus. ‘36 The phenotypes of relatives with the postaxial and preaxial polydactyly or synpolydactyly were the same as that of the proband. In addition, the same anomalies were found in close relatives. We also believe that these types of congenital anomalies have strong hereditary characteristics as others have described.7-9 The fact that the webbing of fingers appears to be strongly related to shortening of the middle phalanges and cleft hand, suggests that these anomalies may be closely related to each other.‘, ‘O-M In our study, the overall recurrence ratio of radial or ulnar ray deficiency was low. However, the phenotype of relatives was very similar to that of the proband in these cases. We think that some implicating factor may exist in the formation of this type of anomaly as previously described.3. ‘5-‘7 In families with the so-called transverse failure of formation, only two families showed limb anomalies among the relatives. In addition, the phenotypes of these relatives were different from that of the proband. One had a duplicated thumb and another had a clasped thumb. This suggests that environmental factors may be more important than genetic ones in the pathogenesis of this type of congenital anomaly.“, ‘* REFERENCES Miura T. A clinical study of congenital anomalies of the hand. The Hand 1981;13:59-69. Czeizel A, Maria Bod, Lenz W. Family study of congenital limb reduction abnormalities in Hungary 1975 1977. Hum Genet 1983;65:35-45. Kelikian H . Congenital deformities of the hand and forearm. Philadelphia: WB Saunders, 1974.
The Journal of HAND SURGERY
4. Miura T. Two families with congenital nail anomalies: nail formation in ectopic areas. J HAND SURG 1978;3:348-51. 5. Miura T. Congenital anomaly of the thumb-unusual bifurcation of the flexor pollicis longus and unusual insertion. J HAND SURG 1981;6A:613-5. 1980; 6. Miura T. Polydactyly in Japan. Handchirurgie 12:39-46. 7. Nicolai J-PA. A family with complex bilateral polysyndactyly. J HAND SURG 1988;13A:417-9. 8. Ofodiele FA: Synpolydactyly in three generation of a Nigerian family. East Afr Med J 1982;59:835-9. 9. Rgemorter NV, Milaire J, Haumont RD, Rodesch F. Familial ectrodactyly and polydactyly: variable expressivity of one single gene-embryological considerations. Clin Genet 1982;22:206-10. 10. Manske PR. Cleft hand and central polydactyly in identical twins: a case report. J HAND SURG 1983;8:906-8. 11. Miura T. Syndactyly and split hand. The Hand 1976; 8:125-30. 12. Miura T. Clinical difference between typical and atypical cleft hand. J HAND SURC 1984;9B:31 l-15. 13. Ogino T. A clinical and experimental study on teratogenic mechanism of cleft hand, polydactyly and syndactyly. J Jpn Orthop Assoc 1979;53:585-43. 14. Watari S , Tsuge K. A classification of cleft hands, based on clinical findings. Plast Reconstr Surg 1979;64:381-9. 15. Chiba A, Miura T. A family with hypotrichosis associated with congenital hypoplasia of the thumb. Jap J Human Genet 1979;24:111-17. 16. Holt M, Oram S. Familial heart disease with skeletal malformations. Br Heart J 1960;22:236-42. 17. Miura T. Congenital familial hypoplastic thumb associated with congenital amputation of the toe. J HAND SURG 1984;9A:420-2. 18. Ogino T, Ishii S, Shiono H. Transverse deficiency of the hand in one of monozygotic twins. The Hand 1981;13:7780.