77 Med Genet 1993; 30: 78-80

Arthrogryposis, ophthalmoplegia, andretinopathy: confirmation of a new type ofarthrogryposis

Constance T R M Schrander-Stumpel, Chris J Howeler, Ad B A Reekers,Nicole M A F A De Smet, Judith G Hall, Jean-Pierre Fryns

AbstractArthrogryposis multiplex congenita is aheterogeneous condition and many dif-ferent types are clinically recognisable.Recently, a new type of autosomal domi-nant arthrogryposis was described in afather and son. We report on a malepatient with similar clinical features,confirming this distinct type of arthro-gryposis. The condition is characterisedby congenital contractures of the handsand feet with diminished or absent pha-langeal creases, ophthalmoplegia, a rigidtrunk, deep set eyes, and (in the oldestpatient) an abnormal electroretinogram.Differential diagnosis from amyoplasia,the different types of distal arthrogrypo-sis, and symphalangism is discussed.(_J Med Genet 1993;30:78-80)

Department ofClinical Genetics,Academic HospitalMaastricht, PO Box1475, 6201 BLMaastricht, TheNetherlands.CTRMSchrander-Stumpel

Department ofNeurology, AcademicHospital Maastricht,Maastricht, TheNetherlands.C J Howeler

Child RehabilitationCenter,Franciscusoord,Valkenburg, TheNetherlands.A B A Reekers

Department ofOphthalmology,Maasland Hospital,Sittard, TheNetherlands.N M A F A De Smet

Department ofPediatrics, BCChildren's Hospital,Vancouver, Canada.J G Hall

Centre for HumanGenetics, Universityof Leuven, Leuven,Belgium.J-P Fryns

Correspondence toDr Schrander-Stumpel.Received 7 April 1992.Revised version accepted5 May 1992.

Arthrogryposis multiplex congenita has beendefined as "congenital, non-progressive limi-tation of movement in two or more joints indifferent body areas".' Over the past 10 years,many different clinical types of arthrogryposishave been delineated2- and recently an appar-

ently new type of arthrogryposis was reportedin a father and son.5 We had the opportunity toobserve the same combination of clinical signsand symptoms in a male patient, confirmingthe existence of this new entity.

Case reportThe proband is the second son of healthy, non-consanguineous Dutch parents. His olderbrother is healthy. Maternal age at the time ofbirth was 27 years and paternal age 35 years. Acousin (the mother's sister's son) was bornwith an isolated right club foot. Pregnancy wascomplicated by hyperemesis gravidarum butno medication was taken. Intrauterine positionwas constant. The mother did not recall speci-fic details of fetal movement or the amount ofamniotic fluid. The birth was normal (exactposition not known) at 36 weeks of gestation,birth weight 2700 g. At birth rigid fingers andbilateral club feet were noticed. In the neonatalperiod a hypertrophic pylorus was surgicallytreated. Several orthopaedic operations wereperformed on both feet, the last time being atriple arthrodesis on both feet in 1982. Despitethe medical problems psychomotor develop-

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Figure 1 Patient at the age of 8 months showing deepset eyes and stifffingers.

*N\.X'.

Figure 2 Patient at the age of 17 years showingreduced muscle mass and hunched, anteverted shoulders.

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Arthrogryposis, ophthalmoplegia, and retinopathy: confirmation of a new type of arthrogryposis

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Figure 3 Face and profile of the patient showing the deep set eyes and broad mo;with thin lips.

ment was normal. A family photograph a

age of 8 months showed the deep set eyesrigid fingers (fig 1). At the age of 6 years h4a triangular face, deep set eyes, and promiears. At the age of 17 years the probandreferred for genetic counselling with a (

nosis of 'arthrogryposis multiplex congei

On clinical evaluation (fig 2) he was a

rigid boy with dry skin. He walked stHeight was 170 cm (3rd to 10th cen

weight 48kg (3rd to 10th centile for heiand head circumference was 55 cm (1Oth (

ile). Both eyes were deep set and thereptosis (fig 3). The palpebral fissures meas2-6cm (normal) and inner canthal disi3 1 cm (normal). There was little facial ex'

sion although motility was normal. Heunable to move his eyes laterally or toupwards. Muscle mass was reduced espe(

in the lower limbs; the shouldershunched and anteverted and the backrigid. He had pectus excavatum. The filwere long and the phalangeal creases

totally absent. Flexion was limited to abot

Figure 4 Hands of the patient showing the longfingers at maximal flexion.

(fig 4). Both lower legs were thin, the left sidemore pronounced than the right. The feetshowed multiple scars from the orthopaedicsurgery. Apart from the ophthalmoplegia, nofurther neurological abnormalities were found.Intelligence was normal. Ophthalmological in-vestigation showed small eyes with amblyopiain the left eye and 6/10 vision in the right eye.A central scotoma could be seen in both eyesand abnormal pigmentation was present inboth retinal maculae. Both eyes showed aDuane anomaly. On electrophysiological ex-amination, the pattern reversal visual evokedresponse showed less response than normal,but was otherwise unremarkable. The flashvisual evoked response was also normal. Theelectroretinogram failed to give any resultbecause of practical problems (painful test forthe patient because of the small, deep set eyes).Chromosomes were normal male 46,XY. Crea-

Muth tine kinase levels were normal. Electromyogra-phy showed no neurogenic or myopathic ab-normalities and conduction velocities of the

h nerves were normal. Radiological examinationst the of the vertebral column showed normal ver-

eand tebrae with limitation of flexion. Radiology of

inehd the hands and wrists showed normal carpalInent bones without fusion, narrow interphalangealdwas joints, and no bony symphalangism (fig 5).

niag- Hearing was normal. CT scan of the brain andlita. orbits showed no abnormalities of the brainlean, and normal eye muscles. CT scan of the

itile), muscles of the upper arm, lower arm, thigh,ight)) and lower leg showed no abnormalities.

cent-was

;ured Discussiontance The clinical features of this patient are verypres- similar to those in the father and son reportedwas by Lai et a15 (table). The facial resemblance oflook the son and the present patient at the age of 6

cially years is striking.were For the differential diagnosis, amyoplasia,was distal arthrogryposis, and symphalangism

ngers were considered in the present patient. Thewere reduced muscle mass, the hunched, antevertedit 300 shoulders, the stiffness of the spine, and the

club feet were very suggestive of amyoplasia;this diagnosis was initially made in the fatherdescribed by Lai et al.5 The ophthalmoplegia,deep set eyes, ptosis, and retinopathy, how-ever, are incompatible with this diagnosis.4 Inthe distal arthrogryposes, a type I and type IIhave been delineated.3 In type I no associatedanomalies are present, intelligence is normal,and inheritance is autosomal dominant. Intype II subdivisions have been made (typeIIA-E) according to the different associatedfindings. Presumed new forms of type II distalarthrogryposis have since been reported butwe could not fit the clinical data of our patientinto any of the clinical types of distal arthro-gryposis.67

Symphalangism can be defined as bony orfibrous ankylosis of interphalangeal jointsresulting in a rigid digit.8 In our opinion, bonyfusion is mandatory for the diagnosis of sym-phalangism in an isolated patient. In the pre-sent patient the interphalangeal joints werenarrow but the phalanges were not fused, thus

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Schrander-Stumpel, H-oweler, Reekers, De Smet, Hall, Fryns

Figure 5 X ray of the hands showing the small interphalangeal joints.

Clinical features of the three patients with a new type of arthrogryposis.

Clinical symptoms Patient 15 Patient 2' Patient 3 (this report)

Sex Male Male Male

Age at diagnosis (y) 27 1-5 18

Normal growth + + +Normal intelligence + + +Reduced muscular mass + + +

Camptodactyly of fingers + + +Long fingers ? + +Absent phalangeal creases ? + +Poorly formed palmar creases ? + +

Limited extension of wrists + + +Limited rotation of forearm + + +Limited extension of large joints + +Dimples over large joints + +

Anteverted shoulders + + +Hunched shoulders + + +Stiff trunk + + +

Pectus deformity + + +

Contractures of feet + + +

Triangular face - + +Deep set eyes - + +Prominent ears - + +Ophthalmopleiga + + +

Abnormal electroretinogram + - +Abnormal retinal pigmentation + - +

on clinical grounds the diagnosis of sympha-langism was excluded.

Different eye abnormalities have been de-scribed in patients with arthrogryposis multi-plex congenita9 but we could find no patientswho combine the eye anomalies and joint limi-tations as seen in the three patients with thetype of arthrogryposis described here and byLai et al.5 A mitochondrial myopathy wassuggested in the patients reported by Lai et aFbecause of the combination of (possibly pro-gressive) ophthalmoplegia and muscular ab-normality.5 In the present patient, followed upfor three years, we have no indication of pro-gression of the condition. In our opinion amitochondrial disturbance is not likely in ourpatient.

Inheritance in the father and son describedby Lai et aP undoubtedly is autosomal domin-ant. Family history in the present patient wasnot informative although a maternal cousinhad serious unilateral club foot. No clinicalsigns of the condition were found in the par-ents and the healthy brother. Paternal age atthe time of birth was 35 years, suggesting anew dominant mutation in the patient.

1 Hall JG. Nicht-chromosomal bedingte dysmorphie syn-drome. Klin Gen Paediatr Mainz Symposium 1980;1:105-21.

2 Hageman G, Jennekens FGI, Vette JK, Willemse J. Theheterogeneity of distal arthrogryposis. Brain Dev1984;6:273-83.

3 Hall JG, Reed SD, Greene G. The distal arthrogryposes:delineation of new entities - review and nosologic discus-sion. Am J Med Genet 1982;11:185-239.

4 Hall JG, Reed SD, Driscoll EP. Amyoplasia: a common,sporadic condition with congenital contractures. Am J7Med Genet 1983;15:571-90.

5 Lai MMR, Tettenborn MA, Hall JG, Smith LJ, Berry AC.A new form of autosomal dominant arthrogryposis. Jf MedGenet 1991;28:701-3.

6 Reiss JA, Sheffield LJ. Distal arthrogryposis type II. Afamily with varying congenital abnormalities. Am 7 MedGenet 1986;24:255-67.

7 Moore CA, Weaver DD. Familial distal arthrogryposis withcraniofacial abnormalities: a new subtype of type II? AmJMed Genet 1989;33:231-7.

8 Matthews S, Famish S, Young ID. Distal symphalangismwith involvement of the thumbs and great toes. Clin Genet1987;32:375-8.

9 Zeiter JH, Boniuk M. Ophthalmologic findings associatedwith arthrogryposis multiplex congenita: case report andreview of the literature. J Pediatr Ophthalmol Strab1989;26:204-8.

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