guadalajara camptodactyly syndrome type ii

7

Click here to load reader

Upload: j-m-cantu

Post on 02-Oct-2016

223 views

Category:

Documents


0 download

TRANSCRIPT

Page 1: Guadalajara camptodactyly syndrome type II

Clinical Genetics 1985: 28: 5460

Guadalajara camptodactyly syndrome

J. M. CANTU', D. GARC~A-CRUZI, J . GIL-VIERA~, Z. NAZARA', M. L. RAM~REZ', M. T. SOLE-PUJOL~ AND J. SANCHEZ-CORONA]

'Division de Genetica, Subjefatura de Investigacion Cientifica, Unidad de Investigacion Biomedica, 2Hospital de Pediatria y 'Hospital de Especialidades, Centro Medico de Occidente, Instituto

Mexican0 del Seguro Social, Guadalajara, Jalisco, Mexico

Two sisters and an unrelated girl presented a distinct intrauterine growth retardation-malfor- mation syndrome with short stature, microcephaly, pectus excavatum, hip dislocation, hypo- plastic pubic region and genitalia, camptodactyly, talipes, shortened 2nd toes, hypoplastic patella and skeletal dysplasia probably due to homozygocity from an autosomal recessive gene.

Received 21 August 1984. revised, uccepted fo r publication 11 March 1985

Key words: Camptodactyly; intrauterine growth retardation; mental retardation; patella agenesis/hypoplasia.

In 1906, Landouzy introduced the term camptodactyly to refer to constitutionally crooked digits (Landouzy 1906) due to a permanent flexion contracture of the proxi- mal interphalangeal joints (Temtamy & McKusick 1978). An autosomal dominant form is known and there are about a dozen of inherited malformation disorders that show camptodactyly (Goodman et al. 1972, Cantu et al. 1980, McKusick 1983). The purpose of this report is to describe three cases (two sisters and one unrelated girl) affected by a probably inherited distinct intrauterine growth retardation-malfor- mation syndrome with camptodactyly. An abstract with data from two of the cases has been already published (Cantu et al. 1981, McKusick 1983).

Case Reports

Cuse A : The 5-year-old proposita (Fig. l a and 2a) was the product of the 1st full-term

pregnancy and dystocic (pelvic presen- tation) delivery. Nanosomy, camptodactyly, absence of flexion of the knee and bilateral talipes were noted at birth. Palpebral ptosis, evident at about three months of age, was surgically corrected as later were the talipes. The father and mother, clinically normal and non-consanguineous, were 25 and 23 years of age, respectively, at the proposita's birth. She has two sisters; one normal, aged 4 years, and Case B.

The psychomotor development has been mildly delayed. The somatometric par- ameters are shown in Table 1 and the clini- cal findings in Table 2. As additional fea- tures the patient showed a small forehead with tiny hairiness, arched eyebrows, thin lips, malformed ears, wide and high palate, short neck, wide thorax, bilateral hypo- plasia of the thenar and hypothenar regions; limited pronation and supination, and mus- cle hypoplasia on the external side in both feet. There was neither palpable patella nor

Page 2: Guadalajara camptodactyly syndrome type II

G U A D A L A J A R A C A M P T O D A C T Y L Y I i 55

Flg. 1. Case A (left) and Case B (right). Note nanosomy, short neck and the appearance at the knee joint in both sibs; right palpebral ptosis in Case A. The sernic- rouched stance is not due to pterygia but to hip dislo- cation.

Table 1

Quantitative Data

CASES

A B C

Age Height (cm) Weight (kg) Circumferences

Cephalic (cm) Thoracic (cm) Abdominal (cm)

Lower segment (cm) Segment ratio Arm span (cm) IQ

5y r 2y r 10mo 87* 73' 10.2" 6.5*

44' 43' 49.5* 47 44.5 48.5 37 30

83 73 75 79

1.35 1.43

5 yr 6 mo 92' 13.4'

48.7' 53 46 40

92 77

1.3

below the 3rd percentile

knee flexion. She also showed an interglu- teal pit and duck-waddle gait.

Fig. 2. Upper: Case A, close up of the hands. See camptodactyly of 2nd to 4th fingers, ulnar deviation of the 2nd and flexion contracture at the metacarpopha- langeal joint of the thumbs. Middle: Case B, close up of the hands. See mild camptodactyly mainly at the 4th and 5th fingers of the left hand, also mild ulnar deviation of the 2nd fingers and flexion contracture at the metacarpophalangeal joint of both thumbs. Lower: Close up of the feet. Case A (left), Case B (right). See overlapped, shortened 2nd toes and plano-valgus foot deformity.

Case B: The proposita's sister, aged 2 years and 10 months (Fig. l b and 2b) was the product of the 3rd full-term pregnancy and normal delivery. A striking clinical simi- larity to her affected sister was noted at birth. She underwent surgical treatment of the talipes at 2 years and 5 months of age and later of the knee limitation (with abnor-

Page 3: Guadalajara camptodactyly syndrome type II

Tab

le 2

Clin

ica

l d

ata

co

mp

are

d w

ith

oth

er

syn

dro

me

s

CA

SE

S

A B

C

G

CS

l SC

DH

PP

ENS

GS

W

FS

THS

G

OS

l SP

S N

PS

O

DD

S C

OFS

K

D

MP

S

NC

S G

OS

-ll

’& N

anos

omy

at b

irth

Sho

rt s

tatu

re

Mic

roce

phal

y P

alpe

bral

pto

sis

Mic

roph

thal

mia

O

cula

r hy

pert

elor

ism

C

lefl

pala

te

Mic

rogn

athi

a or

ret

ro-

mic

rogn

athi

a S

tiffn

ess

of te

mpo

ro-

man

dibu

lar

join

t T

ortic

ollis

B

ony

fusi

on i

n c

ervi

cal

spin

e P

ectu

s ex

cava

tum

S

colio

sis

Hip

dis

loca

tion

Hyp

opla

stic

pub

ic r

egio

n an

d ge

nita

lia

Fle

xion

con

trac

ture

s of

th

e m

etac

arpo

phal

ange

al

join

ts

Cam

ptod

acty

l y U

lnar

dev

iatio

n of

dig

its

Knu

ckle

pad

s S

ynda

ctyl

y N

ail h

ypop

lasi

a Ta

lipes

P

rom

inen

t tal

us

Ove

rlapp

ed to

es

Sho

rten

ed 2

nd to

es

Hyp

opla

stic

or

abse

nt

Mul

tiple

pte

rygi

a M

enta

l ret

arda

tion

pate

lla

++

+

+

++

+

-

+-

+

t

--

++

-

-

--

--

+

+

+-

+

+

++

++

+

+

++

-

-

--

-

-

++

+

+

++

+

+

++

+

+

--

Inhe

ritan

ce

AR A

R A

R

+* -

AD o

r AR

GC

S-I:

Gua

dala

jara

cam

ptod

acty

ly s

yndr

ome

type

I (C

antu

et

al.

1980

); SC

DH

PP:

Syn

drom

e of

cam

ptod

acty

ly, d

war

fism

, hy

pogo

nadi

sm, p

ectu

s ca

rinat

um a

nd

ptos

is (

Tem

tam

y 8 M

cKus

ick

1978

); EN

S: E

mer

y-N

elso

n sy

ndro

me

of s

hort

sta

ture

, fla

t fa

cies

and

dig

ital

cont

ract

ures

(E

mer

y 8.

Nel

son

1970

); G

S:

Gor

don

synd

rom

e (G

ordo

n et

al.

1969

); W

FS:

Whi

stlin

g-fa

ce s

yndr

ome

(Tem

tam

y 8.

McK

usic

k 19

78, C

erve

nka

et a

l. 19

70):

THS:

Tel

Has

hom

er s

yndr

ome

(Goo

dman

et a

l. 19

76);

GO

S-I:

Goo

dman

cam

ptod

acty

ly s

yndr

ome

(Goo

dman

et a

l. 19

72);

SPS:

Sm

all p

atel

la s

yndr

ome

(Sco

tt &

Tao

r 19

79);

NPS

: Nai

l-pat

ella

syn

drom

e (B

ergs

ma

1979

); O

DD

S: O

culo

dent

odig

ital s

yndr

ome

(Tho

den

et a

l. 19

77);

CO

FS:

Cer

ebro

-ocu

lo-f

acio

-ske

leta

l sy

ndro

me

(Pef

ia &

Sho

keir

1978

); K

D:

Kus

kokw

im d

isea

se

(Pet

ajan

et a

l. 19

69);

MPS

: Mul

tiple

pte

rygi

um s

yndr

ome

(Tem

tam

y 8.

McK

usic

k 19

78, S

toll

et a

l. 1980); N

CS:

New

cam

ptod

acty

ly s

yndr

ome

(Bar

aits

er 1

982)

; GO

S-

II: G

oodm

an c

ampt

odac

tyly

. syn

drom

e II

(Roz

in e

t al

. 19

84).

* B

lock

ver

tebr

ae (

T4, 5

and

6).

Page 4: Guadalajara camptodactyly syndrome type II

G U A D A L A J A R A C A M P T O D A C T Y L Y I I 57

Fig. 3. Case C at 4 years of age. Note the striking resemblance to Cases A and 8. Upper: The hands with camptodactyly of the 2nd to 5th fingers and mild flexion contracture of the metacarpophalangeal joint of the thumbs. Lower: See the planovalgus foot deformity, the overlapped and shortened 2nd toes.

ma1 findings as: atrophy of the extensor muscle group, shortened and fibrotic mus- cles with multiple bands to the surrounding structures and rudimentary patella without intercondyleal structures). Psychomotor de- velopment has been mildly delayed. The quantitative and clinical data are shown in Tables 1 and 2, respectively.

Case C: An unrelated girl of 5 years and 6 months of age (Fig. 3), was the product of the 3rd full-term pregnancy and apparently normal delivery, although perinatal data was unavailable. At birth, nanosomy and limitation of the knee movement was evi- dent. The psychomotor development has been delayed. The parents were non-con- sanguineous and the normal mother died in the post-partum period of unknown cause. The father could not be examined but was reported to be normal. The 1st product was a girl who died at 12 months of age of unknown cause and the 2nd pregnancy

ended in a spontaneous miscarriage. The quantitative and clinical data are shown in Tables 1 and 2 , respectively. Clinically, the patient showed similar features to Cases A and B; as additional signs, she presented long eyelashes, endotropia, diastasi recti, hypoplastic palmar dermal ridges, absent distal interphalangeal creases of the 2nd to the 5th fingers, bilateral Sidney’s creases, planovalgus foot deformity, shortened left pelvic limb, pilonidal dimple and several joints limited for a full extension, i.e. elbow, knee and thumbs.

The laboratory examinations in the three cases, including blood cell count, blood and urine chemistries, screening tests for meta- bolic defects (Phenistix, glucose oxidase, Millon, anthrone, ferric chloride, DNPH, nitrosonaphthol, acid albumin turbidity, CTA, methylmalonic acid, Benedic, cyanide nitroprusside), plasma and urine chromato- graphy for sugars and amino acids, serum immunoglobulins, CPK and aldolase deter-

Page 5: Guadalajara camptodactyly syndrome type II

58 C A N T U E T A L .

Fig. 4. Upper: Case A, see the severe scoliosis, wide interpedicular distance at the lumbosacral region; hypoplastic iliac and ischiopubic bones, bilateral dislocation of the hip, slenderness and bands of growth arrest on the long bones and hypoplastic displaced patella. Middle left: Camptodactyly in Case A. Middle right: Case B, see back displaced 2nd metatarsal. Lower: Also back displaced 2nd metatarsal (left Case B and center Case C). Right: Note hypoplastic patella in Case C.

Page 6: Guadalajara camptodactyly syndrome type II

G U A D A L A J A R A C A M P T O D A C T Y L Y I I 59

Table 3

Radiological findings

CASES

A B C

Microcephaly + + + Cuboid-shaped vertebral bodies + + - Wide interpedicular distance

in the lumbosacral region + + - Scoliosis + + + + Spina bifida occulta at L5 - + - Hypoplastic iliac and/or

ischiopubic bones + + + Uni or bilateral dislocation

of the hip + + + Slenderness and bands or growth

arrest on the long bones Hypoplastic, aplastic andlor

displaced patella + + f Back displaced 2nd metatarsal + + + Generalized osteopenia + + + Delayed bone age + + +

+ + +

minations, X-chromatin and karyotype (high resolution G-bands), yielded normal or negative results.

Dermatoglyphic evaluation of Case A re- vealed ATD angles of 45" (right) and 48", ulnar loops on the 3rd and 4th fingers and hypoplastic ridges in the other fingers of the right hand; an arch in the thumb, an ulnar loop in the 4th finger and hypoplastic ridges in the other fingers of the left one; absence of the distal interphalangeal creases of the 2nd to the 5th digits and equivalent simian creases in both hands. The radiological findings are shown in Table 3 (Fig. 4).

Discussion

The clinical and radiological findings in the three girls constitute a syndrome which was compared with all other syndromes with camptodactyly, intrauterine growth retar- dation and multiple malformations and hy- poplasia or agenesis of the patella. Those syndromes with a considerable resemblance to the present cases are shown in Table 2. The Multiple Pterygium Syndrome (MPS) was the closest diagnosis to be discarded,

since some of our patients' features, such as short stature, microcephaly, ptosis of the eyelids, micrognathia and scoliosis, are common to the MPS (as well as to other camptodactyly syndromes); however, the al- most complete absence of pterygia, which in MPS involves neck, axilla, antecubital, popliteal and intercrural areas, the hip dis- location, the flexion contractures of the thumbs, the short 2nd toes and the patellar defect, appear as specific stigmata of the present syndrome. Other camptodactyly syndromes (Temtamy & McKusick 1978, Bergsma 1979, Rozin et al. 1984) were also excluded on the basis of grossly different clinical features. Likewise, syndromes show- ing patellar hypoplasia or agenesis, as the von Recklinhausen syndrome (Smith 1982); and low-birthweight entities as the 3-M slen- der boned nanism (Cantu et al. 1981), Sil- ver-Russel syndrome (Escobar et al. 1978) and Dubowitz syndrome (Dubowitz 1965) were easily discarded by the absence of camptodactyly.

High resolution cytogenetic studies re- vealed normal karyotypes in our patients and thus permitted us to discard a chromo- somal origin of the malformations, spe- cifically, monosomy 2q24.2+q3 105 (Moller et al. 1984), trisomy 8 and trisomy 1Oq (de Grouchy & Turleau 1982) which include camptodactyly in their phenotypic ex- pression.

In conclusion, the intrauterine growth re- tardation-malformation syndrome in the 2 sibs reported here appears as a distinct en- tity, which, Mendelianly thinking, would correspond to an autosomal recessive pat- tern of inheritance.

To designate this syndrome, we would like to propose the term Guadalajara Camptodactyly Syndrome Type 11, since we have previously described a similar disorder as Guadalajara Camptodactyly Syndrome (Cantu et al. 1980), which actually should be named Type I.

Page 7: Guadalajara camptodactyly syndrome type II

60 C A N T U

Acknowledgments

We thank A. Barthel and A. Alcarez for thc art work, and M. E. Goiii for her secretarial assistance.

References

Bergsma, D. (ed.) (1979). Birth Defects Compen- dium. New York, Alan R. Liss, Inc.

Baraitser, M. (1982). A new camptodactyly syn- drome. J. Med. Genet. 19, 4043.

Cantu, J. M., H. Rivera, Z. Nazara, Q. Rojas, A. Hernandez & D. Garcia-Cruz (1980). Guad- alajara camptodactyly syndrome. A distinct probably autosomal recessive disorder. Clin. Genet. 18, 153-159.

Cantu, J . M., D. Garcia-Cruz, J. Sanchez-Cor- ona, R. Fragoso, A. Hernandez & Z. Nazara- Cazorla (1981). 3-M slender boned nanism. A distinct autosomal recessive intrauterine growth retardation syndrome. Am. J. Dis. Child. 135, 905-908.

Cantu, J. M., D. Garcia-Cruz, M. L. Ramirez & M. T. Sole-Pujol (1981). Guadalajara campto- dactyly syndrome type 11. (Abstract). 6th Int. Cong. Hum. Genet. Jerusalem, p. 263.

Cervenka, J., R. J. Gorlin, P. Figalova & J. Far- kasova (1970). Cranio-carpotarsal dysplasia or whistling face syndrome. Arch. Otolaryngol. 91,

deGrouchy, J. & C. Turleau (1982). Atlas des Maladies Chromosomiques, 2tme ed. Paris, Ex- pansion Scientifique Francaise.

Dubowitz, V. (1965). Familial low birthweight dwarfism with an unusual facies and a skin eruption. J. Med. Genet. 2, 12-17.

Emery, A. E. & M. M. Nelson (1970). A familial syndrome of short stature, deformities of the hands and feet, and an unusual facies. J. Med. Genet. 7, 379-382.

Escobar, V., S. Gleiser & D. D. Weaver (1978). Phenotypic and genetic analysis of the Silver- Russel syndrome. Clin. Genet. 13, 278-288.

Goodman, R. M., M. B.-M. Katznelson & E. Manor (1972). Camptodactyly: occurrence in two new genetic syndromes and its relationship to other syndromes. J. Med. Genet. 9, 203-212.

Goodman, R. M., M. B.-M. Katznelson & A. Katznelson (1976). Camptodactyly with mus- cular hypoplasia, skeletal dysplasia, and ab- normal palmar creases: Tel Hashorner camp- todactyly syndrome. J. Med. Genet. 13, 136-141.

183-187.

E T A L .

Gordon, H., D. Davies & M. Berman (1969). Camptodactyly, cleft palate, and club foot. A syndrome showing the autosomal-dominant pattern of inheritance. J. Med. Genet. 6, 266-274.

Landouzy, L. (1906). Camptodactylie: stigmata organique precoce du neuroarthritisme. Presse Mid. 14, 251.

McKusick, V. A. (ed.) (1983). Mendelian Inheri- tance in Man. Baltimore, Johns Hopkins Uni- versity Press.

Moller, M., D. Garcia-Cruz, H. Rivera, J. Sanch- ez-Corona & J. M. Cant6 (1984). Pure mono- somy and trisomy 2q24.24q3105 due to an inv ins (7;2)(q2 1.2;q3 105q24.2) segregating in four generations. Hum. Genet. 68, 77-86.

Pefia, S. D. J . & M. H. K. Shokeir (1978). Auto- soma1 recessive cerebro-oculo-facio-skeletal (COFS) syndrome. Birth Defects: OAS X(7),

Petajan, J. H., G. L. Momberger, J. Aase & D. G. Wright (1969). Arthrogryposis syndrome (Kuskokwim disease) in the eskimo. J A M A

Rozin, M. M., M. Hertz & R. M. Goodman (1984). A new syndrome with camptodactyly, joint contractures, facial anomalies, and skel- etal defects: a case report and review of syn- dromes with camptodactyly. Clin. Genet. 26,

Scott, J. E. & W. S. Taor (1979). The “small patella” syndrome. J. Med. Bone Joint Surg.

Smith, D. W. (ed.) (1982). Recognizable Patterns of Human Malformation. Philadelphia, W. B. Saunders, Co. pp. 377-379.

Stoll, C., J. M. Levy, P. Kehr & M.-P. Roth (1980). Familial pterygium syndrome. Clin. Genet. 18, 317-320.

Temtamy, S. A. & V. A. McKusick (1978). The Genetics of Hand Malformations. New York, Alan R. Liss, Inc.

Thoden, C. J., S. Ryoppy & P. Kuitunen (1977). Oculodentodigital dysplasia syndrome. Acta Paediatr. Scand. 66, 635-638.

51-60.

209, 1481-1486.

342-355.

61, B(2), 172-175.

Address: Dr. J. M . Cantk Division de Genetica Subjefatura de Inv. Cient$ca Instituto Menicano del Seqtrro Social Apartado Postal 1-3838 Guadalajara Jalisco Mexico