The Schwartz-Jampel syndrome (SJS) is a rare congenital multisystem disorder of unknown pathogenesis which is characterized by distinct faces, skeletal deformities, joint contractures, short stature, muscle hypertrophy, clinical myotonia, and continuous muscle fiber activity. The inheritance pattern of SJS has been assumed to be autosomal recessive. We report the occurrence of the classic SJS syndrome in both a father and son in a nonconsanguineous family, suggesting that SJS has the potential for a dominant pattern of inheritance. Key words: Schwartz-Jampel syndrome skeletal deformities myotonia muscle fiber activity, continuous MUSCLE & NERVE 13:1152-1163 1990

SCHWARTZ- JAMPEL SYNDROME W I T H DOMINANT INHERITANCE ROBERT M. PASCUZZI, MD, ROBERTO GRATIANNE, MD, BlAGlO AZZARELLI, MD, and JOHN C. KINCAID, MD

Sc1iwarts-Jampcl syntironicr is ;i r-aiv ciisorcler of iinkiiowii pathogenesis cliarncterizctl by skeletal tie form itics , slio r t stat 11re , joint coi 1t i x t u res , 171itsc:le liypertr-ophy, cliai-actci-isticfiicics, riiusclc stiffness, clinical niyotonia, arid contiiiuous muscle fiber activity. Schwar-tz mid Jmipcl, who iq>oitcd two siblings in 1962 with the c a r d i d manifcst;itions of the synclrome, einphasizetl the ocular findings of n a r r o w palpebral fissures, tcr-met1 I)lc~~I~ai.o~'hitn(,sis."' 'rile iriitial case may liave hccn i q ~ o r t c diii I95 I h y Catcl w h o descri1)ccI t w o sistcrs having muscle, horie, and j o i n t tlisease Lei-met1 dysostosis enchoiitJralis rrietacpihysaria.7 . I'hese patients appear t o have demonstrated the typical features ol' SJS. Al)erfcld rc-reported Sc1iwar.t.z and Jampel's original patients i n lCKi.5 etnpliasi7ing tlic skeletal ahnoi.in~ilities.' 'rhey also cnipliasizctl thc presence of m yotonia. Mereu descrit)ed two sililings with this disorder- in 196'3 and siiggcsred the naiiic Sellwart z -. J;im pt:l T h e inheritance pattern was pre-

From the Departments of Neurology (Drs Pascuzzt, Gratianne. arid Kincaid) and Pathology (Dr. Azrarelli). Indiana University Medical Center, Indianapolis, Indiana Acknowledgment The authors thank Mrs Linda Hagan for assistance in preparation of the manuscript. Address reprint requests to Robert M. Pasci17c1,MD, Department of Neurology. 6th Floor Regenstriel Health Center, 1001 West 10th Street, lndtanapolis, iN 46202. Accepted for publtcatiori Noverriber 24, 1989 CCC 0148-639X/90/01201152 012 $04.00 G 1990 John Wiley & Sons, Inc

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Schwartz-Jampel Syndrome

sumctl t o he aittosonial recessive. FThose t w o sibI t t ~ c ireviewed b y Aberf~cllclc i al. aiitl lat1cIecI as Ilii\rilig cIioritiro tlysiropIiic myotoni;r." Hutteiilocliei- et al. providetl tlic initial observa-

lings were

lion of' c:ontiiiuous electrical activity in muscle at rest cIoc:iitneriteci tiy eIcc.troiriyogr-at)~iy. p icy laheled the tlisortler as osteochondro clysti-ophy. Previous I-epoi-ts have emphasized the ailtosonla1 recessive iri1ierit;iiice patterti of SJS. We report the occiirrence of S j S in a f~ithei-; i t i d son, suggesting the possililit y of cloniirmnt inheritancc.

''

PATIENT #1

A 44 year-old man was referred IOr evaluation of ;I chronic iiciiroIiiiiscii1;ii~ disease in 1!)80. His parents noted h i t ;it birth he had large, prominent iiiusclcs m t l tleveloped pi-ogressivc stiffiiess aflecling tlic: 1iml)s early in childhootl. W h e n he w;is a child, musc:le stiff'ncss affected his gait, arid he had difficulty attempting t o run. His stiffness was iitiafI'ecLet1 b y sustained exercise but aggravated b y (.old exposure. Slowly progressive weakness of tlte limhs, par-ticularly the distal muscles gi-oups, w a s initially rioted diii.iiig adolescence along with early fiitigue during exercise. He sti.uggled in rising fi-om ;i sitting position, in walking, aitcl with line, iq1etitivc u s e of' the ;ii-ins aiitl Iiaiicis, In his ~ O S ,lie noted the tlevelopnicnt of' pei.sisterit low back ant1 proximal leg ac:hing paiii. fIis wilk ohservccl that the distal extixxnitics, p;irticularly the fi ) reaim s ;in tl 11 ;ti irls , s h o w ctl constant I i n e , (111 ive1'ing inoveiiieiits. 'l'hcse persisted during sleep. Heavy ingestion 01' swcet foods rc!sultcd in ;iii i n -

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CI-easein low bac:k and proximal leg wvakri stil'f'ness. Iluring h e p i s t 20 years he has gradua l l y weakened, requiring ;I iiiotorized wheelcliair for motility. Past iiicdical history is notable tor recurrent inguinal lymphadenop~ithyof' irrikiiown etiology. I le is allergic t o quiliiiic, whidi pi-otluces a skin rasli. Family history is r-emarkab~efor ;in affected s o n whose case is presented below. He has no other childr-en. '['here is no otlier Iiistoi-y 101- sirnilarly affected family mernbci-s. T h c patient's lither irrimigrated Irorn Czechoslovakia. Tliere is no evidence o f consanguinity. The paticnl earned ;I college degree and is working as ;in acc'ountant. Examination rcvcalcd nol-ma1 vital signs. Height was 5 leer 4 inches. The fxial cxpr-ession wits fixed with narrow palpebral fissurc:s, small pursed mouth, and Immiinent cycl)i-ows (Fig. 1 ). k i r s were low-set. Range of motion 01' the ncck was markedly limitcd. Chrdiac: exaimination was normal. Tlic chest had a barrel configuration with pectus carinatuni. Contracturcs were preseiit a t the elbows, wrists, hands, and knees (Figs. 2, .3, a r i d 4). 'l'here was mild scoliosis. 1 iigher cortical function was noi-ma1 as were visual fields, funduscopic, light and acconirnotlat.ivt: examination. Tlicr-c was a rnarked exlerrial oplitlialmoplcgia b u t no ptosis. Facial sensalioii w a s normal. Thc smile was limited, suggcst.ing h i f a d woakriess. 'l'he palate, gag, aricl tongue wcr-c 1 ~ 1 r r i i a l , hiit speecti was sli&tly n a s a ~ . 'I'he sternoc1eidorri;istoitt iiiuscles appeal-ecl atrophic. Lirrib inotor examiiiatioii I-c.vc;rlcct W I I t i n Li( )us mt i scl e aclivity tlirou gho LLt , 1110s t p I( I i i i inent in t h e fingers witli ii 1-ippliiig appear-ance to more pruxinial muscles. 'I'lietr-icep, bicep, deltoid, quadricep, abtloininal, pectoralis, a r i t l c:;ilf' iliusc:lcs appe;tr-ed liypertrophic. I-)isLal iiiusclcs w e r e atrop11ic: . M tisc:lc tone was i ncreascd througho ~i t . Thcr-c: was marked perciissiori Iriyotonia in both proximal antl distnl rriusc:lcs. 'I'her-e was rnilcl generxlizecl weakiicss, i11o1-eprominent in distal miisclcs, ;ind iniltl r-eductioti in p o w e r witli pi-olonged cxer-cise. Sensory exariiiiiation was normal. 'I'he gait was stiff and bI-oatl-l);iscd. M I W ~stretch reflexes were nornially active and syiiinietr.ica1 t x i t appeared LO liavc a prolonged relaxation ptuse. 'L'lie toes were downgoing to plantar- stirniilation. Cri.rbrll;tr furictiori was norrnal. I,;il)oratory evaluation iiicluded i i o i - i n a l mniplete I h o d count, Westergl.cn sccliiiiciit.atiori ratc, S M A 12, thyroid furiction tests, scriiiii protein elrc~r.crphoi.esis,a i i t l growth tiorriioIie assay. Ci-eatiiic kinase was elrviited, ranging f'rom 300 t o

Schwartz- Jampel Syndrome

FIGURE 1. Patient #1 demonstrating prominent eyebrows, lowset ears, narrow palpebral fissures, small pursed mouth, and fixed facial expression.

2000 IUIL

or1

rriultiple samples. Urine geiictic

sci-eelis l'or amino acids, auto-oxidation, tyi-osine,

glycosatiiitio~lycaris,ketoacids, sulfhydryl, iind retl ucirig sul>st;irices were normal. 01-gaiiic acid SCITCII was nor-mil. Uronic acid was 1 mg/L (less t l i a i i 1 irig/g c:r-eatinine)(normal range = 0 to 3 3 nigig crcatininc:). ~~let:tr-ocar~lic,gl-arri was normal. Ratliogi-:iphs revealed sliort flat wrtet>ral t)odies antl pigeon-breast defoi-rnity. Nerve coilduction studies revealed motor c:onrluc:tion velocities a t the lower limit of i i o r ~ i i a l in the ariii aricl leg. 'I'he sur;il r-csponse was iioi~rnal.'Tlicv-e was a slight decrcimenl t o 2 Hz repctitivc stimulat i o i i c.)f tlic ulnar riel-ve. Chncenlric ncccllc c:x;imin;itioii slioweti increased insertional activity with needle r i i o v m i e n t eliciting dense trains 01' repelilive t1ist:hai-ges witli a fi-ccluciicy o l ' HO t o 200 Hz (Fig. 5). Similar disch ;t rges occ Li r red without I I ccd I e m c)v e in e 11 t an (I showed waxing-waning frequency and amplitude (Fig. 6). Additionally, t h e were periodic repetitive dischai-ges (myokymic discharges) in several muscles (Fig. 7). Coiriplete electrical silcncc was rare. 'l'he voluntary niotoi- unit poleiitiiils w e r e riorrrial t o slightly enlargccl. Muscle biopsy was pcrformcd on lie riglit cliidriceps and right clcltoid niust.les at age 40 a n d in thc lel'l v;islus later-alis a t age 43. All biopsies showctl similar- firitliiigs cwtisislirig of rriai-ked variation in fiber skc: (I-angirigfrom 10 to 125 microns in diarnctcr) and h l i a p e , fiber necrosis ;ind ~.cgeneration,fiber splitting, increasctl internal nuclei, n~iclcarlxigs, internalizat.ion 01' I h o t l vessels, w h oid cd fit ~er-s,occasion al s m all ;II ig ii la t etl f ibe rs ,

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FIGURE 2. Patient # I .

FIGURE 3. Patient #l.

moth-eaten lillers, a n d inci,eased ent1omysi;il con-

rieclive tissue (Figs. 8 aiid 9). Additional histocliemical siairis including PAS, oil i.ccl 0, A'1'Pase, NADII, MAC:, phosphorylase, m d alkaline phosplialase were Linrenm-kable. Electi-oil micros-

FIGURE 4. Patient #I

copy of oiic specimen showed noimal appcaraiice of sarcolciiiiiial mitochondIia, golgi apparatus, anti ti-iatls. Occasionally, a riorrii;il-appeai.ing fiber contained nucleai. clusters with lipid d i q d e t s a n d groups of' dense LUIILIICS in pai-allel array. Marked

FIGURE 5. Concentric needle EMG of anterior tibialis muscle at rest demonstrating insertion-induced high-frequency discharge with variable rate (80 to 200isec) and variable amplitude best labeled as a neuromyotonic discharge. Bar = 0.1 sec; gain = 50 v.

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Schwartz-Jampel Syndrome

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December 1990

FIGURE 6. Concentric needle EMG of anterior tibialis muscle at rest demonstrating spontaneous waxing and waning high-frequency discharge (maximal rate about 100 per second). Bar = 0.1 sec; gain = 50 p V.

PATIENT # 2

Tlic 12 year-old son of' the piwiously desci-ibetl I x i t i u i t was noted to have pimmincrit iniIscii1atui.c at hirch. HC I i a c t congenital dislocatioii o f the r;iclius ;it ~ l i ce l l ~ o wbilaterally. He also had expeririiccd pi-ogressive dil'liculty w i h stil'l'ness in tlic liirihs m t l limited gait gradually througli c:hiltlhood. I lis school work has been coiisistciitly c:xc.clIc11t.

'l'he examination revealed a short, stocky, muscular-appcaring boy with a short, stiff neck (Fig. 1 I). 'Ihe palpebral fissures w e r e sriiall and the rriouth and lips wci-e pu r~sedin appearance. 'l'he eyebrows were proininent and the ears low-set. C:onti-actures werc pr-csent a~ the elbows, wrists, arid hands. M L I ~ tone C was increasctl tliroughout. Bulk was iiicr-eased proxiinally. Power was normal to slightly reduced. Thci-e was continuous niuscle activity most mai-ked in the haiitls. Pei-c:ussion myotonia was present. Strct.ch I-trllexes were symmetric ;ind nornially active. 'rhc rcmiindci- 01' t 11e ne 11 rological ex;m i n at ion was ri 01-ma1. Laboratory evaluation inclutled n urine inetal,olic screen with normal amino acids, auto-oxiciatioil titer, glyc,os~irninoglycalis,keto acids, sulfhy-

FIGURE 7. Concentric needle EMG of the anterior tibialis rnusde at rest. Spontaneous rhythmic bursts of motor unit potentials (myokymic discharges) at a rate slightly greater than l/second. Bar

Schwartz Jarnpel Syndrome

=

1 sec: gain = 50 mV.

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1155

scribed. (:hoking upon expostire to cold liquids h a s also ~ ~ tIescriIietl. e n "$ Bony delbrniitics are detectable early manilestations of clic disease. 'The spectrum of l m l y abnormalities includes hip clysplasia, kyposc:oliosis, talipus-ct~~iinovarus, pectus carinatus, liigli adiect p l a t e , irregularities of articular surklces, fiattening ol' the femoral licatt, I)l;ityl>iisi:i, arid small flattened vertebral Iiodies. ?'liese bone abnornialities have Ileen noted 10 rcsernhle those of osicochondroclystrophy (Morquio diseasc). Although short staturr: is described as a cxtlirial feature of (he disoi-tler, the height of reported patienis is vari;ible, with many patierits heing only iiiiltlly short. 'The Iicxl c:ii-c.uml.erence (wticn rcpoi-ted) has been riornial. Motor- developmental delay occurs, p:irlic:iilitrly with ambulaiioii. Tlic gait has been notctl to be still' and wide lxiscti. Central nervous systcrii clt:lic:its have been clctcctctl only rarely. Norinal intelligence appears t o Iic: typical. Ilutlerilocher reported a single case with associated Iiydr-ocepI1alus.'-I 'l'he fiicial appeiiixicc is tlil'liciilt LO describe, yet characteristic. Tlic irioiith tends LO t)c smidl wiih pursed lips; the c:hin recedes; the p;ilpebral hssurcs arc ii~ii-row(I.~lepliai-opliiniosis); arid the f? c i: ~ ~ ; icxprcssioii l is re1;itively lixed. Thc hcad

FIGURE 8. Vastus lateralis cross section. There is marked variation in fiber size, increased endomysial tissue, central migration of nuclei and few nuclear bags. H & E ~ 2 5 0 .

tends t o be lilted hack, the ears low lying, ailti t1iel.c. is ;I low positioIi of' the h;tirline o n the fore},eaci~ l l l c l Ilcck. L)ceE)~lOr.,zonral fLII.l.owS ;,cI.oss die forclicad w i t h r;tisetl, prominent, bLisliy eyebrows, and irregulx eyelashes h a v e lieen ernplm-

dryl-rcdiiciiig sul)stariccs, orgaiiic: acids, aiid ui-onic acid. X'he patient has not been evaluated to this date with KMC: or rriiiscle biopsy. DISCUSSION

Althoiigh the c l i i i i d fcatures clescribetl in more than 40 ( m e reports of SJS are variable, those reports containing photographs rcvcal ii striking similarity in t hc: appearance ol' SJS patients. '1';tIde 1 summar-izes the ( : h i ical features in 22 r-eported patients (indutling the present index (:asc). I n gc:ncr;il, the ;tf'tCc:tcct patients are normal a t birth, except fi)r evidence of hoiiy abiioi-nialitics and riiusclc liypci-trophy, as illustratcd in tlic prcsciit casc. Farrcll CL al. desci-ihcd scvci~criiaiiifcstalioiis in a iiconale. '111e majoricy of' case reports suggest that syniptoms ; i d signs are initially noted in Lhe first two t o tlircc years of life arid thcrcaftcr ciilier plateau o r slowly l>r()gr(!ss. F

Schwartz-Jampel syndrome with dominant inheritance.

The Schwartz-Jampel syndrome (SJS) is a rare congenital multisystem disorder of unknown pathogenesis which is characterized by distinct faces, skeleta...
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