Autosomal dominant and sporadic radio-ulnar synostosis

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  • American Journal of Medical Genetics 68:127134 (1997)

    1997 Wiley-Liss, Inc.

    Autosomal Dominant and Sporadic Radio-Ulnar Synostosis

    Renata Rizzo,1* Vito Pavone,2 Giovanni Corsello,3 Giovanni Sorge,1 Giovanni Neri,4 and John M. Opitz5,61Divisione di Neurologia Pediatrica, Clinica Pediatrica, Universit di Catania, Cantania, Italia 2Clinica Ortopedica, Universit di Catania, Catania, Italia 3Istituto Materno Infantile Universit di Palermo, Palermo, Italia4Istituto di Genetica Medica, Universit Cattolica, Roma, Italia 5Foundation for Developmental and Medical Genetics, Helena, Montana 6Medical Humanities, Montana State University, Bozeman

    We report on seven cases of congenital radio-ulnar synostosis (RUS). Five werefound in the same family and two were spo-radic. In six the synostosis was bilateral andconsistently involved the proximal end ofthe radius and ulna. In the familial cases theanomaly was inherited as an autosomaldominant trait and was associated with aDubois sign and relative shortness of meta-carpals number 4 and 5 in two patients, andof number 2 in another patient, and of allphalanges of the 5th fingers. These observa-tions suggest involvement of an ulnar devel-opmental field. RUS does not seem to be rarein the Sicilian population. Am. J. Med.Genet. 68:127134, 1997 1997 Wiley-Liss, Inc.

    KEY WORDS: congenital radio-ulnar syn-ostosis; autosomal dominant;forearm anomaly; Sicily; ul-nar developmental field

    INTRODUCTIONCongenital radio-ulnar synostosis (RUS) impairs

    supination and pronation. It is more often bilateralthan unilateral and is usually sporadic; familial occur-rence is said to be rare [Hansen and Andersen, 1970].About 300 isolated cases have been reported since theoriginal description in 1793 [Finidori et al., 1978; Griffetet al., 1986].

    The Italian Registry on Congenital Malformation (IPIMC) collected one case of RUS within the period1986 1992, in a total of 766,000 births. In this patientthe anomaly was associated with absent left thumb,club hands, right thumb duplication, cervico-vertebralschisis, and anomalous umbilical vessels (Mastroiacovo,

    personal communication). One isolated case was ob-served by Camera in Genova [1997]. However, the fre-quency might be underestimated since the anomaly isnot always recognizable at birth.

    In Sicily, 18 patients with RUS have been observed. Inseven, belonging to two families, RUS was associatedwith microcephaly [Giuffr et al., 1994]; four are syn-dromal cases with Brachmann De Lange syndrome (2),Nager syndrome (1) [Pavone et al., 1988], isotretinoinexposure (1) [Rizzo et al., 1991], and the remainder arethe cases reported here.

    We describe a family with five affected relatives inthree generations. Two unrelated sporadic cases withbilateral and unilateral synostosis, respectively, arealso reported. The familial cases represent a complexform of RUS and lend further support to the hypothe-sized ulnar developmental field.

    CLINICAL REPORTSPatient 1

    R.P., a 1-year-old boy, is the first child of healthy, non-consanguineous Sicilian parents (father 28, mother 26years old). He was delivered at term by caesarean sec-tion after a normal pregnancy. Birthweight was 3,250 g.The neonatal period was uneventful. At 4 months, theparents noted that R.P. was unable to pronate orsupinate his left arm. At 9 months his weight was 9,000 g (50th centile), length was 68 cm (10th centile),and OFC was 45 cm (50th centile). The boy had an ab-normal left arm with deformity of the proximal segmentof the radius and ulna. The physical findings were oth-erwise normal. Roentgenograms showed an abnormalleft elbow joint with deformation and fusion of the prox-imal part of the radius and ulna; the right was normal.Chromosomes were apparently normal.

    Patient 2Z.D., a boy, is the second child of non-consanguineous

    healthy Sicilian parents (father 35, mother 30 yearsold). He has an older, healthy brother. The child wasborn at term with birth weight of 3,850 g, length of 49cm, and an OFC of 34.5 cm. Infancy and childhood were

    *Correspondence to: Dr. Renata Rizzo, Clinica Pediatrica Poli-clinico, Viale A. Doria 6, Catania, Italy 95125.

    Received 16 June 1995; Accepted 10 April 1996

  • uneventful. At 11 years the patient was evaluated forRUS. At that time he had a weight of 40 kg (75th cen-tile), height of 136 cm (10th centile), and an OFC of 53cm (50th centile). He had brachycephaly, a wide fore-head, frontal bossing, decreased antero-posterior diam-eter of thorax, and severe limitation of pronation, andsupination at the elbow and wrist joints. The boy hadborderline intelligence with an I.Q. of 80. There was no taurodontism nor dermatoglyphic abnormalities.Skeletal roentgenograms showed bilateral synostosis ofthe proximal ends of the radius and ulna. Chromo-somes were apparently normal.

    Family FPatients I-1, II-1 (Fig. 1). The father of the pro-

    posita and her paternal grandfather (36 and 70 yearsold, respectively) had severe radio-ulnar synostosiswhich prevented supination and pronation. Both mentended to keep their forearms flexed with the palms fac-ing each other. They were otherwise normal and hadnormal intelligence. The paternal age of these patientswas not advanced when they were conceived. The elbowof patient II-1 is illustrated in Figure 2.

    Patient III-1. F.V., a girl, was born normally atterm after an uncomplicated pregnancy. Ultrasound ex-amination at 18 weeks of gestation did not show anyapparent abnormalities. Her birth weight was 3,500 g,length was 51 cm, and OFC was 35 cm. Her first yearsof life were uneventful. At 11 years her weight was 37kg (50th75th centile), height was 142 cm (50th cen-tile), and OFC was 52 cm (50th centile). Her foreheadwas narrow and there was a midline facial capillaryhemangioma. She kept her forearms flexed (Fig. 3) andpronation and supination were virtually impossible.Her performance in school was reported to be poor andshe had severe difficulty in writing, in spite of an I.Q. of100. Roentgenograms showed bilateral synostosis ofthe proximal ends of the radius and ulna extendingover a length of 4 cm. The carpal bones were normalwith no synostosis. A Dubois sign (tip of 5th finger prox-imal to the DIP joint of the 4th digit) was present andthere was relative hypoplasia/shortness of metacarpals4 and 5 (Fig. 4) and of both 5th fingers. Metacarpopha-langeal profile analysis confirmed this impression (Fig.5). Results of a chromosome analysis and of other labo-ratory tests were normal.

    Patient III-3. F.E., a girl, was born at term after anuneventful gestation. Her birth weight was 3,200 g,

    length was 50 cm, and OFC was 34 cm. Ultrasound ex-amination at 18 weeks of gestation did not show anyabnormalities. The first years of life were uneventfuland psychomotor development was normal. At 8 yearsher weight was 27 kg (75th centile), height was 114 cm(3rd centile), and OFC was 50 cm (50th centile). Prona-tion and supination were severely limited (Fig. 6). Theanomaly appeared identical in both forearms. A gradeII/VI systolic murmur could be heard precordially. Her

    128 Rizzo et al.

    Fig. 1. Pedigree of family F shows occurrence in three successivegenerations with AD inheritance.

    Fig. 2. Patient II-1. Roentgenograms of upper limb. Note proximalradio-ulnar synostosis.

    Fig. 3. Patient III-1. Note severe limitation of supination of fore-arms and hands.

  • I.Q. was 110. Roentgenograms demonstrated bilateralradio-ulnar synostosis with proximal fusion that ex-tended distally for about 3 cm (Fig. 7). The carpal boneswere normal and without synostosis (Fig. 8). Metacar-pophalangeal profile analysis documented shortness ofmetacarpal 2 and of all phalanges of the 5th fingers(Fig. 9). Chromosomes were apparently normal.

    Patient III-5. F.A., the proposita, was born at termafter an uneventful gestation. Her birth weight was3,400 g, length 51 was cm, and OFC was 35 cm. An ul-trasound examination at 18 weeks of gestation did notshow any apparent skeletal abnormalities. The neona-

    tal period was uneventful and psychomotor develop-ment was normal. At 4 years her weight was 16 kg(50th centile), height was 93.5 cm (10th centile), andOFC was 49 cm (25th centile). Supination and prona-tion were limited. Clinodactyly of the fifth fingers and aright simian crease were also evident. Roentgenogramsshowed bilateral synostosis between the proximal endsof the radius and ulna; carpal bones were normal withno synostosis. A Dubois sign was present. Shortness ofmetacarpals 4 and 5 was confirmed by metacarpopha-langeal profile analysis (Fig. 10).

    DISCUSSION

    Congenital radio-ulnar synostosis (RUS) is an anom-aly that causes limitation of all movements of the fore-arm with consequent impairment of hand use. Prona-tion and supination of the forearm are limited orabsent. This anomaly may be associated with other defects such as abnormalities of the olecranon, the clav-icles, the ribs, and the sternum [Temtamy and McKusick,1978], dislocation of the hip, knee, and foot [Mercer,1950; Freyer, 1966], and syndactyly and polydactyly[Wilkie, 1914; Mercer, 1950; Freyer, 1966]. In patientswith RUS a high frequency of associated malformationsin other organs such as the heart and urinary tract hasbeen reported [Carroll and Louis, 1974]. RUS is seen ina number of aneuploid syndromes, particularly thoseinvolving abnormal numbers of X and Y chromosomes[Cleveland et al., 1969; Schinzel, 1984; De Grouchy and Turleau, 1984]. RUS can be seen in several non-aneuploidy syndromes. The London DysmorphologyDatabase lists 37 conditions with this anomaly, includ-

    Radio-Ulnar Synostosis 129

    Fig. 4. Patient III-1. Note Dubois sign and relative hypoplasia of4th and 5th metacarpals.

    Fig. 5. Patient III-1. Metacarpophalangeal profile analysis documents shortness of metacarpals 4,5.

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