American Journal of Medical Genetics 36398-403 (1990)
Brief Clinical Report
Two Siblings With Tel Hashomer Camptodactyly and Mitral Valve Prolapse Helga V. Toriello, James V. Higgins, Thomas Malvitz, and Donald F. Waterman Blodgett Memorial Medical Center (T.M., D.F.W.) and Genetics Services, Butterworth Hospital (H.V.T.,D.F.W.), Grand Rapids, and Department of Pediatrics and Human Development, Michigan State University, E . Lansing (H.V.T.,J.V.H.) CLINICAL REPORTS Patient 1 The propositus is a 15Vz year-old Hispanic boy who was born a t term. Birthweight was 2,400 g (3rd centile) and length was 53.5 cm (90th centile). He had clubfeet and bilateral cryptorchidism, which have since been repaired. Strabismus and “optic nerve disorder” on the left were diagnosed at an early age. He has had repeated shoulder and elbow dislocations, several “extra” teeth were extracted, and a lipoma was removed from the knee. KEY WORDS autosomal recessive inheriOn physical examination, height, weight, and occiptance, connective tissue deitofrontal circumference (OFC) were normal (2540th fects, multiple congenital centile). He had bilateral ptosis, downslanting palanomalies pebral fissures, hypertelorism (inner canthal distance 4.5 cm, outer canthal distance 12 cm, both above the 97th centile), highly arched palate, reduced thoracic kyphosis, asymmetric muscle hypoplasia, narrow shoulINTRODUCTION ders, hyperextensible small joints, soft tissue syndacWe describe a brother and sister with Tel Hashomer tyly, hypoplastic or absent distal interphalangeal camptodactyly syndrome (THC) and mitral valve pro- creases, highly arched feet, and soft, loose skin which lapse (MVP), a previously undescribed association. scarred easily (Figs. 1-3). Span was 157 cm as comMVP is relatively common in adults, with a prevalence pared to a height of 168 cm. An echocardiogram demonof 5% in some populations, although the prevalence in strated an MVP. Intellectual development is normal. Dermatoglyphic evaluation showed the pattern dechildren (15 years or less) is less than 1%[Devereux et al., 19821. Although it is usually a benign condition, scribed as typical for THC [Pagnan et al., 19881. There there may be a predisposition to bacterial endocarditis were large whorls on each digit, A-D triradii, vertical [Bor and Himmelstein, 19841 or progression to mitral a, b, and t lines, multiple white lines, and 2 palmar valve insufficiency [Malcolm, 19851. There is a clear whorls on each hand. association of MVP with connective tissue disorders, Patient 2 and in a recent study it was noted that 72% of patients with MVP had other connective tissue defects; 45% of His younger sister was born 11years ago following an those investigated had abnormal skin collagen ratios as uneventful gestation; she weighed 2,400 g and had a well [Child et al., 19861. length of 50 cm. She also had clubfeet which were surWe suggest that MVP is a previously undescribed gically corrected, as well as malocclusion and “extra” manifestation of THC, and that one of the pleiotropic teeth. Several lipomas have been removed from her effects of the THC allele is on connective tissue. knee, and shoulder and elbow dislocations occur frequently. On physical examination she had a facial appearance similar to that of her brother, but different from that of Received for publication January 25, 1989; revision received other relatives. Present were hypertelorism (inner canthal distance 4.25 cm, outer canthal distance, 11.5 cm, January 26, 1990. both 97th centile), highly arched palate, tapering digits Address reprint requests to Dr.Helga V. Toriello, Genetics Serwith hyperflexibility, hypoplastic or absent distal intervices, 21 Michigan St., Suite 350, Grand Rapids, MI 49503. A brother and sister with Tel Hashomer camptodactyly and mitral valve prolapse are described. Mitral valve prolapse is heterogenous, but appears to occur more frequently in individuals with connective tissue disorders. The presence of mitral valve prolapse as a component manifestation of Tel Hashomer camptodactyly suggests that abnormal connective tissue is a pleiotropic effect of the mutant allele.
0 1990 Wiley-Liss, Inc.
Tel Hashomer Camptodactyly
399
phalangeal creases, slight syndactyly, winged scapulae, and a span less than height (142cm vs. 149 cm) (Figs. 4-6). Echocardiogram demonstrated MVP with mild insufficiency. Hand radiographs of both children did not demonstrate symphalangism, but did show soft tissue syndactyly. Dermatoglyphics were also similar to those of her brother, in that she had 9 large whorls and 1 ulnar loop, A triradius, vertical a, b, and t lines, and multiple white lines. Family history is negative for similar findings; in particular, an echocardiogram on each parent did not demonstrate MVP. Table I lists the findings in both children.
Fig. 1. Patient 1. Note facial appearance.
Fig. 4. Patient 2. Note similar facial appearance to that of Patient 1. Fig. 2. Patient 1. Note DIP contractures, absent DIP creases.
TABLE I. Comparison of Findings in Both Patients
Fig. 3. Patient 1. Note syndactyly, tapering digits.
Finding Ptosis Hypertelorism Strabismus Optic atrophy Highly arched palate Malocclusion with accessory teeth Reduced thoracic kyphosis Muscle hypoplasia Mitral valve prolapse Mitral insufficiency Cryptorchidism Syndactyly DIP contracture Hypoplastic IP creases Joint hyperflexibility Joint dislocations Lipomas Soft, loose skin
Patient 1
+ + +
+ + + t t
+ + t + + t t
+ +
Patient 2 -
t -
t t -
t t t
NA
+ + + t + + +
400
Toriello et al. TABLE 11. Mitral Valve Prolapse Syndromes
Name Cutis laxa Ehlers-Danlos I
I1
111 VI VIII X Fragile X Osteogenesis imperfecta I I11 IV
Connective tissue findings Loose, sagging skin Easy bruising, prominent scars, joint hypermobility, soft, hyperextensible skin, herniae, varicose veins Easy bruising, joint hypermobility, soft skin with moderate hyperextensibility herniae, varicose veins Soft skin, marked joint hypermobility, varicose veins, herniae Scoliosis, ocular fragility, soft hyperextensible skin, hypermobile joints Skin fragility with abnormal scars, moderate joint laxity, periodontitis Soft, mildly hyperextensible skin, mild joint laxity, easy bruising Hyperelastic skin, hypermobile joints, pectus, highly arched palate, large ears
Skin lesions, angioid streaks in eye Clubfoot, contractures, scoliosis, myopia, crumpled ear
Marfan syndrome
Striae, myopia, retinal detachment, highly arched palate, pectus, scoliosis, herniae, hypermobile joints, arachnodactvlv Striae, slight skin hyperextensibility, myopia, highly arched palate, dental crowding, pectus, scoliosis, joint laxity, joint dislocations Prominent joints, myopia, highly arched palate
Stickler syndrome
MVP syndrome Cohen syndrome
Mental retardation, autistic-like behavior
Frequent fractures, hearing loss, blue sclerae Scleral and bone fragility, bone deformities Frequent fractures, hearing loss
Pseudoxanthoma elasticum Contractural arachnodactyly
Marfan hypermobility syndrome
Other findings
Myopia, highly arched palate, scoliosis, absent thoracic kyphosis, pectus Joint laxity, highly arched palate, scoliosis, lordosis, hiatal hernia
Forney syndrome
Highly arched palate, deafness, dental crowding, joint fusions
Pfeiffer-Palm-Teller syndrome
Highly arched palate, cupshaped ears, limited joint mobility
Reference Pyeritz [1986]
Inheritance AD
Shohet et al. [1987]
AD
Shohet et al. [19871
AD
Shohet et al. [1987]
AD
Pyeritz [19861
AR
Pyeritz [19861
AR
Arneson et al. [1980]
AR
Loehr et al. [1986]
XL
Tsipouras and Ramirez [1987] Tsipouras and Ramirez [19871 Tsipouras and Ramirez t19871 Lebwohl et al.
AD ?AR, AD AD AD
[19821
Midface hypoplasia, cleft palate, sensorineural deafness
Ramos-Arroyo et al. [ 19851; Anderson et al. [1984] Pyeritz [1986]
AD
Walker et al. [1969]
AD
Liberfarb and Goldblatt [19861
AD
Schutte et al. [1981]; Salomon et al.
AD
AD
[19751
Short stature, truncal obesity, strabismus, short philtrum, prominent incisors, mental retardation Freckling, iris pigmentary changes, exotropia, short stature Enamel hypoplasia, highly pitched voice, brachydactyly, short stature, hypertonia
Mehes et al. [1988]
AR
Forney et al. t19661
AD
Pfeiffer et al. [19771
AR
(Continued)
Tel Hashomer Camptodactyly
401
TABLE 11. Mitral Valve Prolapse Syndromes (Continued) Name Tamminga syndrome
Connective tissue findings Myopia, limited knee and elbow movement
Furlong syndrome
Myopia, highly arched palate, scoliosis, herniae, joint contractures, arachnodactyly
Shprintzen-Goldberg syndrome
Pliable ears, pectus, herniae, joint contractures, arachnodactyly
Sugarman-Vogel syndrome"
Hyperextensible skin, highly arched palate, pectus, herniae, joint hypermobility, arachnodactyly, genu recurvatum
J affer-Eleighton syndrome"
highly arched palate, dental crowding, pectus, joint hypermobility, arachnodactyly, soft skin
Lymphedemahypoparathyroidism syndrome
Cantalamessa syndrome
Highly arched palate
Other findings Cerebral atrophy, apparently lowset ears, deep-set eyes, iris dysplasia, optic coloboma, mental retardation, hypotonia Craniosynostosis, proptosis, hypertelorism, hypospadias Craniosysnostosis, strabismus, exophthalmos, maxillary and mandibular hypoplasia, hypertelorism, optic atrophy, lowset ears, cryptorchidism, mental retardation Hypertelorism, strabismus, exophthalmos, micrognathia, lowset ears, cryptorchidism, clinodactyly, hypotonia Brachydactyly
Reference Tamminga et a1 119851
Short stature, telecanthus, ptosis, congenital lymphedema, hypoparathyroidism, nephropathy, brachytelephalangy Short stature, low posterior hairline, short neck, cubitus valgus, short 4th metacarpal, gonadal failure. mild mental retardation
~
Inheritance ?
Furlong et al. [1987] ?
Shprintzen and Goldberg [19821
?
Sugarman and Vogel [1981]
?
Jaffer and Beighton [1983]
?
Dahlberg et al. [1983]
AR or XL
Cantalamessa et al. [1989]
AR or XL
"MVP has not been described in these syndromes, but because of phenotypic similarity to syndromes included in the table, these conditions were also included.
DISCUSSION Our diagnostic approach was to first review all syndromes with MVP, using both the London Dysmorphology Database and a literature review (Table 11). No conditions with a similar phenotypic pattern were found. However, entry of the findings into the POSSUM Database system by Dr. Agnes Bankier suggested a diagnosis of THC. THC is a rare autosomal recessive condition first described by Goodman et al. 119721. Pagnan et al. [19881 recently summarized the 11 previously reported cases and noted that relatively consistent (90%) findings in THC include short stature, mild facial asymmetry, hy-
pertelorism, small mouth, highly arched palate, dental crowding, thoracic scoliosis, winged scapulae, syncamptodactyly, tapered fingers, muscle hypoplasia, and abnormal dermatoglyphics. These features were also present in our patients. In addition, our patients had a span less than height; accessory teeth; multiple lipomas; soft, stretchy, easily scarred skin; and MVP which have not been previously described as manifestations of MVP. Although Patton et al. l.19861 found deficiency of type 2b muscle fibers and suggested that the primary effect of the gene was on muscle tissue, it is also possible that there is also an effect on connective tissue since many of the phenotypic features of THC (highly arched palate, thoracic scoliosis,joint dislocations, and pes planus) are
402
Toriello et al.
Fig. 5. Patient 2. Note DIP contractures, absent DIP creases.
Fig. 6. Patient 2. Note mild syndactyly, tapering digits.
also consistent with a connective tissue dysplasia. The additional manifestations of soft skin and MVP in the sibs reported here further support this hypothesis. MVP is common, and it is possible that it is a chance association in these sibs; however, the lack of MVP in either parent and the relative rarity of this finding in children suggest that it is more likely a component manifestation of THC. It is also clear that MVP can be but one manifestation of a generalized connective tissue disorder, and that component manifestations need not be limited to connective tissue defects. Therefore, an individual with a suspected connective tissue disorder, even in the presence of other, presumably non-connectivetissue defects, should have an echocardiogram searching for MVP; conversely, any patient with MVP should have a thorough physical examination searching for evidence of other connective-tissue-related anomalies.
Furlong J , Kurczynski TW, Hennessy J R (1987):New Marfanoid syndrome with cranio-synostosis. Am J Med Genet 26599-604. Goodman RM, Katznelson MB-M, Manor E (1972): Camptodactyly: Occurrence in two new genetic syndromes and its relationship to other syndromes. J Med Genet 9:203-212. Jaffer Z, Beighton P (1983): Syndrome identification case report 98: Arachnodactyly,joint laxity, and spondylolisthesis.J Clin Dysmorphol 1:14-18. Lebwohl MG, Distefano D, Proleau PG, Uram M, Yannuzzi LA, Fleischmajer R (1982): Pseudoxanthoma elasticum and mitral valve prolapse. N Engl J Med 307:228-231. Liberfarb RM, Goldblatt A (1986):Prevalence of mitral valve prolapse in the Stickler syndrome. Am J Med Genet 24:387-392. Loehr JP, Synhorst DP, Wolfe RR, Hagerman R J (1986):Aortic root dilatation and mitral valve prolapse in the fragile X syndrome. Am J Med Genet 23:189-194. Malcolm AD (1985):Mitral valve prolapse associated with other disorders. Causal coincidence, common link, or fundamental genetic disturbance? Br Heart J 53:353-362. Mehes K, Kosztolanyi G, Kardos M, Horvath M (1988): Cohen syndrome: A connective tissue disorder? Am J Med Genet 31:131-133. Pagnan NAB, Gollop TR, Lederman H (1988):The Tel Hashomer camptodactyly syndrome: Report of a new case and review of the literature. Am J Med Genet 29:411-417. Patton MA, McDermott KD, Lake BD, Baraitser M (1986):Tel Hashomer camptodactyly syndrome: Report of a case with myopathic features. J Med Genet 23:268-271. Pfeiffer RA, Palm D, Teller W (1977): A syndrome of short stature, amimic facies, enamel hypoplasia, slowly progressive stiffness of the joints, and high-pitched voice in two siblings. J Pediatr 91:955-957. Pyeritz RE (1986):Heritable disorders of connective tissue. In Pierpont ME, Moller J H (eds): “Genetics of Cardiovascular Disease.” New York: Martinus Nijhoff Publ. pp. 265-303. Ramos-Arroyo MA, Weaver DD, Beals RK (1985):Congenital contractural arachnodactyly: Report of four additional families and review of the literature. Clin Genet 27570-581. Salomon J, Shah A, Heinie RA (1975):Thoracic skeletal abnormalities in idiopathic mitral valve prolapse. Am J Cardiol 36:32-36. Schutte J E , Gaffney FA, Blend L, Blomquist CG (1981): Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med 71533-538. Shohet I, Rosenbaum I, Frand M, Duskin D, Engelberg S, Goodman RM (1987): Cardiovascular complications in the Ehlers-Danlos syndrome with minimal external findings. Clin Genet 31:148-152. Shprintzen RJ, Goldberg RB (1982):A recurrent pattern syndrome of cranio-synostosis associated with arachnodactyly and abdominal hernias. J Craniofac Genet Dev Biol 255-74.
REFERENCES Anderson RA, Koch S, Camerini-OteroRD (1984):Cardiovascular findings in congenital contractural arachnodactyly: Report of a n affected kindred. Am J Med Genet 18:265-271. Arneson MA, Hammerschmidt DE, Furcht L, King RA (1980):A new form of Ehlers-Danlos syndrome: Fibronectin corrects defective platelet function. J Am Med Assoc 244:144-147. Bor DR, Himmelstein DU (1984):Endocarditis prophylaxis for patients with mitral valve prolapse: A quantitative analysis. Am J Med 76:711-717. Cantalamessa L, Baldini M, Ambrosi B, Fraccaro M (1989): A syndrome of primary gonadal failure, short stature, mitral valve prolapse, and mental retardation. Am J Med Genet 33:117-120. Child AH, Burleigh M, Leech G, Leatham A (1986): Generalised collagen deficiency in patients with mitral valve prolapse (abstract).J Med Genet 23:469. Dahlberg PJ, Borer WZ, Newcomer KL, Yutuc WR (1983):Autosomal or X-linked recessive syndrome of congenital lymphedema, hypoparathyroidism, nephropathy, prolapsing mitral valve, and brachytelephalangy. Am J Med Genet 1699-104. Devereux RB, Brown WT, Kramer-Fox R, Sachs I(1982):Inheritance of mitral valve prolapse: Effect of age and sex on gene expression. Ann Intern Med 97:826-832. Forney WR, Robinson SJ,Pascoe DJ 11966): Congenital heart disease, deafness, and skeletal malformations: A new syndrome? J Pediatr 68:14-26.
Tel Hashomer Camptodactyly S u g m a n G, Vogel MW (1981):Craniofacial and musculoskeletal abnormalities: A questionable connective tissue disease. Synd Ident 7:16-17. Tamminga P, Jennekens FGI, Barth PG, Fleury P, Van den Berg H, Oorthuys JWE (1985): An infant Mith Marfanoid phenotype and congenital contractures associated with ocular and cardiovascular
403
anomalies, cerebral white matter hypoplasia, and spinal axonopathy. Eur J Pediatr 143:228-231. Tsipouras P, Ramirez F (1987): Genetic disorders of collagen. J Med Genet 24:2-8. Walker BA, Beighton PH, Murdoch J L (1969): Marfanoid hypermobility syndrome. Ann Intern Med 71:34g-352,
Brief Clinical Report
Two Siblings With Tel Hashomer Camptodactyly and Mitral Valve Prolapse Helga V. Toriello, James V. Higgins, Thomas Malvitz, and Donald F. Waterman Blodgett Memorial Medical Center (T.M., D.F.W.) and Genetics Services, Butterworth Hospital (H.V.T.,D.F.W.), Grand Rapids, and Department of Pediatrics and Human Development, Michigan State University, E . Lansing (H.V.T.,J.V.H.) CLINICAL REPORTS Patient 1 The propositus is a 15Vz year-old Hispanic boy who was born a t term. Birthweight was 2,400 g (3rd centile) and length was 53.5 cm (90th centile). He had clubfeet and bilateral cryptorchidism, which have since been repaired. Strabismus and “optic nerve disorder” on the left were diagnosed at an early age. He has had repeated shoulder and elbow dislocations, several “extra” teeth were extracted, and a lipoma was removed from the knee. KEY WORDS autosomal recessive inheriOn physical examination, height, weight, and occiptance, connective tissue deitofrontal circumference (OFC) were normal (2540th fects, multiple congenital centile). He had bilateral ptosis, downslanting palanomalies pebral fissures, hypertelorism (inner canthal distance 4.5 cm, outer canthal distance 12 cm, both above the 97th centile), highly arched palate, reduced thoracic kyphosis, asymmetric muscle hypoplasia, narrow shoulINTRODUCTION ders, hyperextensible small joints, soft tissue syndacWe describe a brother and sister with Tel Hashomer tyly, hypoplastic or absent distal interphalangeal camptodactyly syndrome (THC) and mitral valve pro- creases, highly arched feet, and soft, loose skin which lapse (MVP), a previously undescribed association. scarred easily (Figs. 1-3). Span was 157 cm as comMVP is relatively common in adults, with a prevalence pared to a height of 168 cm. An echocardiogram demonof 5% in some populations, although the prevalence in strated an MVP. Intellectual development is normal. Dermatoglyphic evaluation showed the pattern dechildren (15 years or less) is less than 1%[Devereux et al., 19821. Although it is usually a benign condition, scribed as typical for THC [Pagnan et al., 19881. There there may be a predisposition to bacterial endocarditis were large whorls on each digit, A-D triradii, vertical [Bor and Himmelstein, 19841 or progression to mitral a, b, and t lines, multiple white lines, and 2 palmar valve insufficiency [Malcolm, 19851. There is a clear whorls on each hand. association of MVP with connective tissue disorders, Patient 2 and in a recent study it was noted that 72% of patients with MVP had other connective tissue defects; 45% of His younger sister was born 11years ago following an those investigated had abnormal skin collagen ratios as uneventful gestation; she weighed 2,400 g and had a well [Child et al., 19861. length of 50 cm. She also had clubfeet which were surWe suggest that MVP is a previously undescribed gically corrected, as well as malocclusion and “extra” manifestation of THC, and that one of the pleiotropic teeth. Several lipomas have been removed from her effects of the THC allele is on connective tissue. knee, and shoulder and elbow dislocations occur frequently. On physical examination she had a facial appearance similar to that of her brother, but different from that of Received for publication January 25, 1989; revision received other relatives. Present were hypertelorism (inner canthal distance 4.25 cm, outer canthal distance, 11.5 cm, January 26, 1990. both 97th centile), highly arched palate, tapering digits Address reprint requests to Dr.Helga V. Toriello, Genetics Serwith hyperflexibility, hypoplastic or absent distal intervices, 21 Michigan St., Suite 350, Grand Rapids, MI 49503. A brother and sister with Tel Hashomer camptodactyly and mitral valve prolapse are described. Mitral valve prolapse is heterogenous, but appears to occur more frequently in individuals with connective tissue disorders. The presence of mitral valve prolapse as a component manifestation of Tel Hashomer camptodactyly suggests that abnormal connective tissue is a pleiotropic effect of the mutant allele.
0 1990 Wiley-Liss, Inc.
Tel Hashomer Camptodactyly
399
phalangeal creases, slight syndactyly, winged scapulae, and a span less than height (142cm vs. 149 cm) (Figs. 4-6). Echocardiogram demonstrated MVP with mild insufficiency. Hand radiographs of both children did not demonstrate symphalangism, but did show soft tissue syndactyly. Dermatoglyphics were also similar to those of her brother, in that she had 9 large whorls and 1 ulnar loop, A triradius, vertical a, b, and t lines, and multiple white lines. Family history is negative for similar findings; in particular, an echocardiogram on each parent did not demonstrate MVP. Table I lists the findings in both children.
Fig. 1. Patient 1. Note facial appearance.
Fig. 4. Patient 2. Note similar facial appearance to that of Patient 1. Fig. 2. Patient 1. Note DIP contractures, absent DIP creases.
TABLE I. Comparison of Findings in Both Patients
Fig. 3. Patient 1. Note syndactyly, tapering digits.
Finding Ptosis Hypertelorism Strabismus Optic atrophy Highly arched palate Malocclusion with accessory teeth Reduced thoracic kyphosis Muscle hypoplasia Mitral valve prolapse Mitral insufficiency Cryptorchidism Syndactyly DIP contracture Hypoplastic IP creases Joint hyperflexibility Joint dislocations Lipomas Soft, loose skin
Patient 1
+ + +
+ + + t t
+ + t + + t t
+ +
Patient 2 -
t -
t t -
t t t
NA
+ + + t + + +
400
Toriello et al. TABLE 11. Mitral Valve Prolapse Syndromes
Name Cutis laxa Ehlers-Danlos I
I1
111 VI VIII X Fragile X Osteogenesis imperfecta I I11 IV
Connective tissue findings Loose, sagging skin Easy bruising, prominent scars, joint hypermobility, soft, hyperextensible skin, herniae, varicose veins Easy bruising, joint hypermobility, soft skin with moderate hyperextensibility herniae, varicose veins Soft skin, marked joint hypermobility, varicose veins, herniae Scoliosis, ocular fragility, soft hyperextensible skin, hypermobile joints Skin fragility with abnormal scars, moderate joint laxity, periodontitis Soft, mildly hyperextensible skin, mild joint laxity, easy bruising Hyperelastic skin, hypermobile joints, pectus, highly arched palate, large ears
Skin lesions, angioid streaks in eye Clubfoot, contractures, scoliosis, myopia, crumpled ear
Marfan syndrome
Striae, myopia, retinal detachment, highly arched palate, pectus, scoliosis, herniae, hypermobile joints, arachnodactvlv Striae, slight skin hyperextensibility, myopia, highly arched palate, dental crowding, pectus, scoliosis, joint laxity, joint dislocations Prominent joints, myopia, highly arched palate
Stickler syndrome
MVP syndrome Cohen syndrome
Mental retardation, autistic-like behavior
Frequent fractures, hearing loss, blue sclerae Scleral and bone fragility, bone deformities Frequent fractures, hearing loss
Pseudoxanthoma elasticum Contractural arachnodactyly
Marfan hypermobility syndrome
Other findings
Myopia, highly arched palate, scoliosis, absent thoracic kyphosis, pectus Joint laxity, highly arched palate, scoliosis, lordosis, hiatal hernia
Forney syndrome
Highly arched palate, deafness, dental crowding, joint fusions
Pfeiffer-Palm-Teller syndrome
Highly arched palate, cupshaped ears, limited joint mobility
Reference Pyeritz [1986]
Inheritance AD
Shohet et al. [1987]
AD
Shohet et al. [19871
AD
Shohet et al. [1987]
AD
Pyeritz [19861
AR
Pyeritz [19861
AR
Arneson et al. [1980]
AR
Loehr et al. [1986]
XL
Tsipouras and Ramirez [1987] Tsipouras and Ramirez [19871 Tsipouras and Ramirez t19871 Lebwohl et al.
AD ?AR, AD AD AD
[19821
Midface hypoplasia, cleft palate, sensorineural deafness
Ramos-Arroyo et al. [ 19851; Anderson et al. [1984] Pyeritz [1986]
AD
Walker et al. [1969]
AD
Liberfarb and Goldblatt [19861
AD
Schutte et al. [1981]; Salomon et al.
AD
AD
[19751
Short stature, truncal obesity, strabismus, short philtrum, prominent incisors, mental retardation Freckling, iris pigmentary changes, exotropia, short stature Enamel hypoplasia, highly pitched voice, brachydactyly, short stature, hypertonia
Mehes et al. [1988]
AR
Forney et al. t19661
AD
Pfeiffer et al. [19771
AR
(Continued)
Tel Hashomer Camptodactyly
401
TABLE 11. Mitral Valve Prolapse Syndromes (Continued) Name Tamminga syndrome
Connective tissue findings Myopia, limited knee and elbow movement
Furlong syndrome
Myopia, highly arched palate, scoliosis, herniae, joint contractures, arachnodactyly
Shprintzen-Goldberg syndrome
Pliable ears, pectus, herniae, joint contractures, arachnodactyly
Sugarman-Vogel syndrome"
Hyperextensible skin, highly arched palate, pectus, herniae, joint hypermobility, arachnodactyly, genu recurvatum
J affer-Eleighton syndrome"
highly arched palate, dental crowding, pectus, joint hypermobility, arachnodactyly, soft skin
Lymphedemahypoparathyroidism syndrome
Cantalamessa syndrome
Highly arched palate
Other findings Cerebral atrophy, apparently lowset ears, deep-set eyes, iris dysplasia, optic coloboma, mental retardation, hypotonia Craniosynostosis, proptosis, hypertelorism, hypospadias Craniosysnostosis, strabismus, exophthalmos, maxillary and mandibular hypoplasia, hypertelorism, optic atrophy, lowset ears, cryptorchidism, mental retardation Hypertelorism, strabismus, exophthalmos, micrognathia, lowset ears, cryptorchidism, clinodactyly, hypotonia Brachydactyly
Reference Tamminga et a1 119851
Short stature, telecanthus, ptosis, congenital lymphedema, hypoparathyroidism, nephropathy, brachytelephalangy Short stature, low posterior hairline, short neck, cubitus valgus, short 4th metacarpal, gonadal failure. mild mental retardation
~
Inheritance ?
Furlong et al. [1987] ?
Shprintzen and Goldberg [19821
?
Sugarman and Vogel [1981]
?
Jaffer and Beighton [1983]
?
Dahlberg et al. [1983]
AR or XL
Cantalamessa et al. [1989]
AR or XL
"MVP has not been described in these syndromes, but because of phenotypic similarity to syndromes included in the table, these conditions were also included.
DISCUSSION Our diagnostic approach was to first review all syndromes with MVP, using both the London Dysmorphology Database and a literature review (Table 11). No conditions with a similar phenotypic pattern were found. However, entry of the findings into the POSSUM Database system by Dr. Agnes Bankier suggested a diagnosis of THC. THC is a rare autosomal recessive condition first described by Goodman et al. 119721. Pagnan et al. [19881 recently summarized the 11 previously reported cases and noted that relatively consistent (90%) findings in THC include short stature, mild facial asymmetry, hy-
pertelorism, small mouth, highly arched palate, dental crowding, thoracic scoliosis, winged scapulae, syncamptodactyly, tapered fingers, muscle hypoplasia, and abnormal dermatoglyphics. These features were also present in our patients. In addition, our patients had a span less than height; accessory teeth; multiple lipomas; soft, stretchy, easily scarred skin; and MVP which have not been previously described as manifestations of MVP. Although Patton et al. l.19861 found deficiency of type 2b muscle fibers and suggested that the primary effect of the gene was on muscle tissue, it is also possible that there is also an effect on connective tissue since many of the phenotypic features of THC (highly arched palate, thoracic scoliosis,joint dislocations, and pes planus) are
402
Toriello et al.
Fig. 5. Patient 2. Note DIP contractures, absent DIP creases.
Fig. 6. Patient 2. Note mild syndactyly, tapering digits.
also consistent with a connective tissue dysplasia. The additional manifestations of soft skin and MVP in the sibs reported here further support this hypothesis. MVP is common, and it is possible that it is a chance association in these sibs; however, the lack of MVP in either parent and the relative rarity of this finding in children suggest that it is more likely a component manifestation of THC. It is also clear that MVP can be but one manifestation of a generalized connective tissue disorder, and that component manifestations need not be limited to connective tissue defects. Therefore, an individual with a suspected connective tissue disorder, even in the presence of other, presumably non-connectivetissue defects, should have an echocardiogram searching for MVP; conversely, any patient with MVP should have a thorough physical examination searching for evidence of other connective-tissue-related anomalies.
Furlong J , Kurczynski TW, Hennessy J R (1987):New Marfanoid syndrome with cranio-synostosis. Am J Med Genet 26599-604. Goodman RM, Katznelson MB-M, Manor E (1972): Camptodactyly: Occurrence in two new genetic syndromes and its relationship to other syndromes. J Med Genet 9:203-212. Jaffer Z, Beighton P (1983): Syndrome identification case report 98: Arachnodactyly,joint laxity, and spondylolisthesis.J Clin Dysmorphol 1:14-18. Lebwohl MG, Distefano D, Proleau PG, Uram M, Yannuzzi LA, Fleischmajer R (1982): Pseudoxanthoma elasticum and mitral valve prolapse. N Engl J Med 307:228-231. Liberfarb RM, Goldblatt A (1986):Prevalence of mitral valve prolapse in the Stickler syndrome. Am J Med Genet 24:387-392. Loehr JP, Synhorst DP, Wolfe RR, Hagerman R J (1986):Aortic root dilatation and mitral valve prolapse in the fragile X syndrome. Am J Med Genet 23:189-194. Malcolm AD (1985):Mitral valve prolapse associated with other disorders. Causal coincidence, common link, or fundamental genetic disturbance? Br Heart J 53:353-362. Mehes K, Kosztolanyi G, Kardos M, Horvath M (1988): Cohen syndrome: A connective tissue disorder? Am J Med Genet 31:131-133. Pagnan NAB, Gollop TR, Lederman H (1988):The Tel Hashomer camptodactyly syndrome: Report of a new case and review of the literature. Am J Med Genet 29:411-417. Patton MA, McDermott KD, Lake BD, Baraitser M (1986):Tel Hashomer camptodactyly syndrome: Report of a case with myopathic features. J Med Genet 23:268-271. Pfeiffer RA, Palm D, Teller W (1977): A syndrome of short stature, amimic facies, enamel hypoplasia, slowly progressive stiffness of the joints, and high-pitched voice in two siblings. J Pediatr 91:955-957. Pyeritz RE (1986):Heritable disorders of connective tissue. In Pierpont ME, Moller J H (eds): “Genetics of Cardiovascular Disease.” New York: Martinus Nijhoff Publ. pp. 265-303. Ramos-Arroyo MA, Weaver DD, Beals RK (1985):Congenital contractural arachnodactyly: Report of four additional families and review of the literature. Clin Genet 27570-581. Salomon J, Shah A, Heinie RA (1975):Thoracic skeletal abnormalities in idiopathic mitral valve prolapse. Am J Cardiol 36:32-36. Schutte J E , Gaffney FA, Blend L, Blomquist CG (1981): Distinctive anthropometric characteristics of women with mitral valve prolapse. Am J Med 71533-538. Shohet I, Rosenbaum I, Frand M, Duskin D, Engelberg S, Goodman RM (1987): Cardiovascular complications in the Ehlers-Danlos syndrome with minimal external findings. Clin Genet 31:148-152. Shprintzen RJ, Goldberg RB (1982):A recurrent pattern syndrome of cranio-synostosis associated with arachnodactyly and abdominal hernias. J Craniofac Genet Dev Biol 255-74.
REFERENCES Anderson RA, Koch S, Camerini-OteroRD (1984):Cardiovascular findings in congenital contractural arachnodactyly: Report of a n affected kindred. Am J Med Genet 18:265-271. Arneson MA, Hammerschmidt DE, Furcht L, King RA (1980):A new form of Ehlers-Danlos syndrome: Fibronectin corrects defective platelet function. J Am Med Assoc 244:144-147. Bor DR, Himmelstein DU (1984):Endocarditis prophylaxis for patients with mitral valve prolapse: A quantitative analysis. Am J Med 76:711-717. Cantalamessa L, Baldini M, Ambrosi B, Fraccaro M (1989): A syndrome of primary gonadal failure, short stature, mitral valve prolapse, and mental retardation. Am J Med Genet 33:117-120. Child AH, Burleigh M, Leech G, Leatham A (1986): Generalised collagen deficiency in patients with mitral valve prolapse (abstract).J Med Genet 23:469. Dahlberg PJ, Borer WZ, Newcomer KL, Yutuc WR (1983):Autosomal or X-linked recessive syndrome of congenital lymphedema, hypoparathyroidism, nephropathy, prolapsing mitral valve, and brachytelephalangy. Am J Med Genet 1699-104. Devereux RB, Brown WT, Kramer-Fox R, Sachs I(1982):Inheritance of mitral valve prolapse: Effect of age and sex on gene expression. Ann Intern Med 97:826-832. Forney WR, Robinson SJ,Pascoe DJ 11966): Congenital heart disease, deafness, and skeletal malformations: A new syndrome? J Pediatr 68:14-26.
Tel Hashomer Camptodactyly S u g m a n G, Vogel MW (1981):Craniofacial and musculoskeletal abnormalities: A questionable connective tissue disease. Synd Ident 7:16-17. Tamminga P, Jennekens FGI, Barth PG, Fleury P, Van den Berg H, Oorthuys JWE (1985): An infant Mith Marfanoid phenotype and congenital contractures associated with ocular and cardiovascular
403
anomalies, cerebral white matter hypoplasia, and spinal axonopathy. Eur J Pediatr 143:228-231. Tsipouras P, Ramirez F (1987): Genetic disorders of collagen. J Med Genet 24:2-8. Walker BA, Beighton PH, Murdoch J L (1969): Marfanoid hypermobility syndrome. Ann Intern Med 71:34g-352,
