American Journal of Medical Genetics 46:341-344 (1993)

Brief Clinical Report Inguinal Hernia and Atrial Septa1 Defect in Tel Hashomer Camptodactyly Syndrome: Report of a New Case Expanding the Phenotypic Spectrum of the Disease

P. Franceschini, M.P. Vardeu, F. Signorile, A. Testa, A. Guala, D. Franceschini, and L. Dalforno Zstituto di Discipline Pediatriche, Servizw di Genetica Clinica, Universitd di Torino, Torino, Italy

We report on a girl with Tel Hashomer camp- todactyly syndrome (THCS) born to first- cousin parents. In addition to the usual fmd- ings, the patient had bilateral inguinal hernia and atrial septal defect, not previously de- scribed as component manifestations of the syndrome.

The present description expands the phe- notypic spectrum of the syndrome and gives new support to the hypothesized pleiotropic effects of the THCS gene on connective tissue. 0 1993 Wiley-Liss, Inc.

KEY WORDS: autosomal recessive inheri- tance, connective tissue de- fect, pleiotropic effects

~ ~ _ _ _ _ _ _____ ~ ~ ~

INTRODUCTION The Tel Hashomer camptodactyly syndrome (THCS),

first described by Goodman et al. [19721, is charac- terized by camptodactyly, muscle hypoplasia, skeletal anomalies, and abnormal palmar creases. Additional cases were reported by Goodman et al. [19761, Gollop and Colletto [19841, Patton et al. [19861, Qlki- Szymanska [1986], Pagnan et al. [1988], and Toriello et al. [19901.

Except for the patients described by Pagnan et al. [19881, by Patton et al. [19861, and by Toriello et al. [19901, all the others were born to consanguineous par- ents, suggesting autosomal recessive inheritance.

We report on a patient with THCS born to first-cousin parents, who, in addition to the classical clinical picture, also had inguinal herniae and congenital heart defect (atrial septal defect), not previously reported in the syn- drome.

Received for publication July 17, 1992; revision received Octo- ber 20, 1992.

Address reprint requests to Piergiorgio Franceschini, Istituto di Discipline Pediatriche, Servizio di Genetica Clinica, Universita di Torino, Piazza Polonia 94, 10126 Torino, Italy.

CLINICAL REPORT The proposita was the third child born to normal,

consanguineous (first cousins) parents age 35 years (father) and 19 years (mother) at the time of her birth. Pregnancy and delivery were uneventful. Birthweight was 3,150 g, length 49 cm. At birth she was noted to have bilateral middle finger camptodactyly. The neonatal course and subsequent psychomotor development were normal.

At 4 years heart evaluation was requested because of insufficient weight gain; it showed a large atrial septal defect, which was repaired. Bilateral inguinal hernia was corrected one year later.

At 9 years, a pelvic X-ray, performed because of pain- less limping, showed an anteverted left hip with Perthes- like alterations of the femoral head. The lesion was treated with traction, followed by corrective osteotomy of the femoral neck. Since then the patient has been in good condition.

On examination at age 17 years her measurements were: height 155.5 cm (10th-25th centile); weight 42 kg ( ~ 3 r d centile); OFC 52 cm (3rd centile); a complete re- cord of the antropometric measurements is reported in Table I. Muscle mass was generally reduced (Fig. 1). She had mild facial asymmetry (Fig. 21, long philtrum, small mouth, high-arched palate, and dental crowding (Fig. 3). She had camptodactyly of the middle fingers (milder on right hand because of partial surgical correction), minimal soft tissue syndactyly, brachydactyly, tapering fingers, and clinodactyly of fifth fingers (Fig. 4). The thenar and hypothenar eminences were underdeveloped as well as all the hand and arm muscles.

The feet showed generalized brachydactyly, broad first toes, and overlap of second and third toes (Fig. 5).

Dermatoglyphics showed bilateral transverse palmar creases, numerous additional palmar creases (so called “white lines”), and ulnar diplacement of t triradius (Fig. 6). Intelligence was apparently normal.

The metacarpophalangeal profile of the right hand is shown in Figure 7. As it can be seen, Z values are all below the mean. Shortness is most evident at the second metacarpal, the first, second, and third proximal pha-

0 1993 Wiley-Liss, Inc.

342 Franceschini et al.

TABLE I: F’roposita’s Anthropometric Measurements

Items Value Centi1eB.D. Weight 42 kg <3 Height 155.5 cm 10-25 Head circumference 52 cm 3 Occipital-frontal diameter 18.2 cm 50 Biparietal diameter 13.5 cm <3 Frontal-temporal diameter 10.4 cm 25 Bizygomatic distance 11.6 cm <3 Bigonial distance 8.3 cm -4 S.D. Inner canthal distance 2.8 cm 3-10 Outer canthal distance 8.4 cm <3 Nasal length 4.8 cm 10 Nasal width 2.8 cm 3 Nasal protrusion 3.1 cm 25 Nasion-stomion 7 cm 25 Nasion-menton 11.5 cm 25 Mouth width 4.2 cm 3 Lips height 2cm 50-75 Ear length 5.3cm 3-10 Ear width 3 cm 75 Chest width 21 cm 3 Chest anteroposterior diameter 16.5 cm 25-50 Bi-iliac distance 26 cm 25 Arm length 67.5 cm 25 Hand length 15.5 cm -3 S.D. Right leg length 89 cm 25-50 Left leg length 87 cm 25-50 small mouth. Foot length 21.5 cm 3-10

Middle finger length 6 cm <3 Fig. 2. Patient’s face showing mild asymmetry, long philtrum, and

Fig. 3. Patient’s face showing asymmetry of nasal septum, highly arched palate, and dental crowding.

Fig. 1. Total body appearance ofthe patient: note general reduction of muscle mass. langes, the second and third middle, and the fourth and

fifth distal phalanges.

DISCUSSION The THCS is a rare autosomal recessive condition.

Only 14 patients have been so far reported. As the

Tel Hashomer Camptodactyly 343

Fig. 4. Patient’s hands with brachydactyly, camptodactyly of mid- dle fingers, clinodactyly of fifth fingers, and minimal soft tissue syndac- tYlY.

Fig. 6. Dermatoglyphics of the right hand showing transverse pal- mar crease, ulnar displacement of t triradius, and numerous additional palmar creases (so called white lines).

Fig. 5. Patient’s feet: generalized brachydactyly, big first toes, and overlapping of second on third toes.

number of patients increases the spectrum widens, “old findings change their relative weight, and new patho- genetic hypotheses are suggested. The most consistent findings of the syndrome are: facial asymmetry, ocular hypertelorism, long philtrum, small mouth, highly arched palate, “spindle-shaped” fingers, camptodactyly, and abnormal dermatoglyphics. Brachycephaly, short stature, dental crowding, and thoracic scoliosis are not as constant manifestations as inferred from earlier de- scriptions (Table 11). More recent findings, such as joint hyperflexibility, joint dislocation, loose skin, mitral valve prolapse [Toriello et al., 19903, inguinal hernia, and atrial septa1 defect (present description) have been added.

The basic defect of the syndrome is still unknown. Comparing THCS with all other genetic disorders

including camptodactyly, Goodman et al. [ 19761 found,

Fj * - 3 c 0

-4 -I . . . . . . . , . , . . . , , . . . . I 2 3 4 5 1 2 3 4 6 2 3 4 6 1 2 3 4 6 I--- METACARPAL PROXIMAL MIDDLE DISTAL

Fig. 7. Patient’s metacarpophalangeal profile.

as a common denominator, the involvement of connec- tive tissue, as suggested by such findings as highly arched palate, thoracic scoliosis, joint dislocations, and pes planus.

Patton et al. [1986], on the basis of muscle histology made on one patient showing deficiency of type 2b mus-

344 F'ranceschini et al.

TABLE 11. Clinical Findings in Patients With THCS and Their ResDective Freauencies*

Patient Age SeX

1 2 3 4 5 6 7 8 9 1 0 1 1 1 2 1 3 1 4 17 13 20 19 7 9 13 13 10 4 4 14 11 17 Frequency F M F F F M F M F F F M F F % dZ"

Clinical findings Highly arched palate + + + + + + + + + + + + + + 100 (14/14) Camptodactyly + + + + + + + + + + + + + + 100 (14/14) Spindle-shaped fingers + + + + + + + + + + + + + + 100 (14/14) Abnormal dermatolglyphics + + + + + + + + + + + + + 92.8 (13/14) Muscle hypoplasia + + + + + + + + + + + + + 92.8 (13/14) Ocular hypertelorism + + + + + + + + + + 85.7 (12/14) Facial asymmetry + + + + + + + + + + + 85.7 (12/14) Small mouth + + + + + + + + + + + 85.7 (12/14) Syndactyly + + + + + + + + + + + 78.5 (11114) Long philtrum + + + + + + + + + + + 78.5 (11/14)

+ 78.5 (11/14) Winging of scapulae + + + + + + + + + + + 71.4 (10/14) Dental crowding + + + + + + + + +

Clubbed feet + + + + + + + + + + 71.4 (10114) 71.4 (10114) Short stature + + + + + + + + + + 71.4 (10/14) Thoracic scoliosis + + + + + + + + + +

+ + + + 64.2 (9/14) Brachycephaly + + + + + Malformed toes + + + + + + + + 64.2 (9/14) Prominent forehead + + + + + + + + 64.2 (9114) Clinodactyly + + + + + + + + + 64.2 (9/14) Pes planus + + + + + + + + 57.1 (8/14) Brachydactyly of thumbs + + + + 28.5 (4/14) Dislocated radii + + + 21.4 (3/14) Mitral valve prolapse + + 14.3 (2114) Joint hyperilexibility + + 14.3 (2/14) Joint dislocation + + 14.3 (2/14) Lipomas + + 14.3 (2/14) Soft loose skin + + 14.3 (2/14) Ptosis + 7.1 (1/14) Strabismus + 7.1 (1/14) Optic atrophy + 7.1 (1114) Dysplastic femoral head + 7.1 (1/14) Atrial septa1 defect + 7.1 (1114) Inguinal hernia + 7.1 (1/14)

*Patients: 1-4 [Goodman et al., 1972,19761; 5,6 [Gollop and Colletto, 19841; 7-9 [Tylki-Szymanska, 19861; 10 [Patton et al., 19861; 11 [Pagnan et al., 19881; 12, 13 [Toriello et al., 19901; 14 [personal observation]. 'n, number of patients with the sign; z, total number of patients.

cle fibers, suggested an embryological failure of muscle development as the possible cause of the syndrome.

Manifestations such as joint hyperflexibility, joint dislocation, Soft loose skin, mitral valve Prolapse as found in Toriello et al.'s [ 19901 patients, together with inguinal hernia and a dvsdastic femoral head Dresent

Goodmann RM, Katznelson MB, Hertz M, Katznelson A (1976): Camp- todactyly, with muscular hypoplasia, skeletal dysplasia, and abnor- mal palmar creases: Tel Hashomer camptodactyly syndrome. J Med Genet 13:3:~6-141.

Goodmann RM, Katznelson MB, Manor E (1972): Camptodactyly: Oc- currence in two new genetic syndromes and its relationship to other syndromes. Med Genet 9:203-212.

inour patient, bring new &ppod to the hypoth& of a possible connective tissue involvement.

in " X S . Clearly, more cases need to be cd~erved before one can acceDt this malformation as Dart of the disease

Pagnan NAB, Gallop TR, Lederman H (1988): The Tel Hashomer camp- todactyly syndrome: Report of a new case and review of the litera- ture. Am J Med Genet 29411-417.

Patton MA, McDermot KD, Lake BD, Baraitser M (1986): Tel Hasho- mer camptisdactyly syndrome: Report of a case with myopathic features. J Med Genet 23:268-271.

defect has not been reported

spectrum or -dismiss it as pure chance association. Toriello HV, Higgins JW, Malvitz T, Waterman DF (1990): Two siblings with Tel Ha.shomer camptodactyly and mitral valve prolapse. Am J

REFERENCES Med Genet 36:398-403. Tylki-Szymanska A (1986): Three new cases of Tel Hashomer camp

todactyly syndrome in one Arabic family. Am J Med Genet 23: 759-763.

h l l o p TR, Colletto GMDD (1984): The Tel Hashomer CamPtodaCtYlY syndrome in a consanguineous Brazilian family. Am J Med Genet 17:399-406.