PARTIAL DELETION OF THE LONG ARM OF CHROMOSOME E-18

(1)

(

Received January 28; accepted for publication May 11, 1970.)

Supported in part by U.S. Public Health Service research grant lID 00516.

ADDRESS: (J.P.C.) Department of Pediatrics, Medical Center, Baldwin Avenue, Jersey City, New

Jersey 07304.

PEI)IATRICS, Vol. 46, No. 5, November 1970 721

PARTIAL

DELETION

OF

THE

LONG

ARM

OF

CHROMOSOME

E-18

John

P. Curran,

M.D.,

Farouk

L. Al-Salihi,

M.D.,

and

P.

W. Allderdice,

Ph.D.

From the Department of Pediatrics, Medical Center, Jersey City, New Jersey and the Department of

Obstetrics and Gynecology, College of Physicians and Surgeons,

New

York, New York

ABSTRACT.

A

male infant with growth failure and multiple somatic abnormalities is described.

Karyotype showed deletion of material from the

long arm of an autosome identified autoradiograph-ically as a number 18.

Abnormalities commonly associated with this

chromosome deletion have been mental

retarda-tion, growth failure, microceplialy, hypertrophic ear parts, mid-face retraction, increased digital whorls, developmental retardation, ocular anoma-lies, fusiform fingers, carp mouth, hypoplastic ear

canals, and genital abnormalities occurring in

males.

The subject of this report presented with

ex-treme growth failure and developmental

retarda-tion. Mid-face dysplasia was mild and

microce-phaly was absent. External genitalia were normal

though

all previously described males had

cryptor-chidisni

or penis abnormality. Findings not previ-ously reported are ankylosis in extension of both knees, palatal pigmentation, and an extra thoracic

vertebrum.

Phenotypic analyses of patierlts with an 18q-or 18r chromosome suggest that genie loci

influenc-ing the development of ear canals and the

inci-dence of digital whorls are located near the ends of the long arms. Pediatrics, 46:721, 1970,

CUTIOMO-SOMES, CHROMOSOMES E, CHROMOSOME.S 16-18,

CHROMOSOME ABNORMALITIES, KAROTYPINC,

DELE-TION.

D

E GROUCHY,

et

al.1

in

1964

were

first

to

call

attention

to a patient

with

partial

deletion

from

the

long

arm

of a single

auto-some

18. When

Lejeune,

et al.2

reported

two

cases

clinically

and

cytologically

sinii-lar

in

1966,

the

entity

was

established

as

a

syndrome.

Common

features

have

been

mental

retardation,

growth

and

develop-mental

failure,

microcephaly,

mid-face

dys-plasia,

fusiform

fingers,

high

incidence

of

fingertip

whorls,

anomalies

of

the

ears

and

eyes, and genital abnormalities in males.

The

purpose

of this

paper

is to describe

a

patient

with

this

chromosomal

aberration

who

presents

with

somatic

abnormalities

that

differ

in

some

respects

from

the

syn-dronie

previously

described.

CASE

REPORT

J. B.

is a 3 10/12 old Caucasian male with

Se-vere growth and developmental retardation. He

was born after an estimated gestation of 39 weeks. Birth weight was 2,591 gm. The infant fed poorl, cried weakly, and slept a great deal. At 2 months

weight was 3,636 gm., and at 4 months a heart

murmur was heard. At age 15 months he weighed

5,260 gm., and did not sit, stand, walk, or talk. A

grade Ill/VI short systolic ejection murmur was

noted at the left sternal border, loudest at

intercos-tal spaces 3 and 4. Chest X-ray revealed an

en-larged heart with increased pulmonary blood flow.

At 22 months of age weight was 6,190 gm. At

this time marked limitation of flexion of both knees (less than 10#{176}

)

was noted which, according to the mother, appeared at about 14 months. He sat )Oorly, i)Ut

did

not crawl, stand, walk, or talk.

Family

History

The mother was a 22-year-old Gravida

II,

Para

II. A

4-year-old daughter by a previous husband is normal. Both parents are alive and well.

Physical

Examination

The patient is a 3-vear-10-month-old poorly de-veloped Caucasian male. He appeared active, alert, smiled often, and was interested in his

surround-ings.

lIe responded to requests, but his vocabulary was limited to less than 10 words. Objects were

handled clumsily. He was able to stand and

walk

with wide-based, unsteady gait. Height was 82.5

cm (below the third percentile) and weight was

(2)

ap-Fic. 1. Right ear with well rolled helix, prominent anti-helix and anti-tragus,

and

small tragus.

722

CHROMOSOME 18q-DELETION SYNDROME

Peared low set vith the vertical axis slanted poste-rioriv. There was a well roiled helix, prominent anti-helix and anti-tragus, and a small tragus

(

Fig.

1

)

. The nasal root was broad, the tip elevated,

with mild retraction of tile mid-facial structures

and a small mandible

(

Fig. 2 ). The mouth was

carp-like and tile philtrum was absent (Fig. 3). A

highly arched pilate was speckled with many

deeply pigmented irregular macules 1 to 5 mm in size. There was a 5 cm patch of lighter colored hair over the iiiicloccipital area. The eyes appeared hsperteloric with horizontal fissures and no epican-thus. Eye grounds were normal. Both thumbs were I)r0xinlally (lisplaced and held in the palmar plane. Dimpling over the heads of the third metacarpals

was noted On the dorsal surface of both hands.

Fingers were 5I)ifldle-shaPed. Both knees were

ankiyosed in extension and the third toe was over-lapped by the fourth toe bilaterally. Muscle tone was nornial. A grade Ill/VI systolic ejection mur-mur was heard over the left second intercostal space at the sternal border with a loud, widely split second sound at the pulmonic area.

Laboratory Data

Examination of the blood and urine was normal.

Intravenous urogram revealed no abnormalities.

Chest x-rays revealed an enlarged heart with

prom-inence in the area of the left pulmonary artery seg-ment, increased pulmonary vascularitv, and 13 tho-racic ribs with 13 normal thoracic vertebrae

(

Fig.

4). Radiographic skeletal survey and bone age

were within normal limits at age 6 months, showed no maturation in the hands and wrists at 2 years, 2

months, and maturation and development were

compatible with 6 months at 3 years. The bones

appeared poorly mineralized. No blood group

stud-ies

were done on

the

patient or his parents.

Dermatoglyphic

Examination

Dermatoglyphic studies showed six whorls and

four ulnar loops n the digits and single palmar fiexion creases bilaterally.

Cytogenetic

Studies

Karyotvpes from :3-day cultured leukocytes

showed a partial deletion of the long arm of an

E-group chromosome (46,XY,Eq-) (Fig. 5). For

(3)

non-over-I

Fic. 2. Small mandible, backward tilt of ears, mild mid-face retraction, and absent microcephaly are demonstrated.

lapping and the deleted chromosome was nlorpho-logically distinct from the Y chromosonie and the

C-group chromosomes. The slide was then

re-stained with aceto-orcein, coated with AR 10 strip-ping film, exposed in the dark at 4#{176}Cfor 10 days, and developed in D 19.

The two chromosomes 16 had normal

morphol-ogy and were heavily labeled. Among the four

other E-group chromosomes, the deleted chromo-some was one of the most heavily labeled in 19 of 20 cells (Table I and Figure 6).

We concluded that the deleted chromosome was

an 18q-.

The parents were not studied cytologically.

DISCUSSION

Wertelecki,

et al.

have

tabulated

the

ab-normalities

associated

with

the

loss

of long

arm material from a single autosome 17 to

18 as mental retardation, atretic ear canals,

prominent

anti-helix

and!

or

anti-tragus,

nystagmus, retinal abnormalities, short

stat-nrc,

microcephaly,

mid-face

dysplasia,

hy-potonia,

congenital

heart

disease,

and

a

high

incidence

of

fingertip

whorls.

Lafour-cade and Lejeune4 listed mental

retarda-tion,

somatic

hypotrophy,

microcephaly,

mid-face dysplasia, hypes-trophy of ear

parts,

carp

mouth,

fusiform

fingers,

sub-acromial

dimples,

and

a high

frequency

of

whorls.

Kushnick

and

Matsushita

found

mental

retardation,

short

stature,

microce-phaly, hypotonia, mid-face dysplasia,

prominent

anti-helix

and/or

anti-tragus,

El

(4)

Fic. 3. Carp mouth and absent philtrum.

724 CHROMOSOME

18q-DELETION

SYNDROME

‘1’AiHE

I

(;ItAIN COUNTS OVER CIfRoMoSoniis 17 AND 18 IN TWENTY CELLS

(/tromo.somne.s ranked b,j

(‘cli grain count 1) ci ci ed

number

---

-

_- chromosome

1 2 .3

1 3 7 ii H

5 7 13 16

3 ‘3 ii S

4 0 0 i 0

5 4 7 11 14

6 3 7 13 14

7 0 1 9 10

S 4 7 11 7

9 0 1 10 2

10 1 4 10 H

11 4 7 S Ii

12 2 4 H 13

13 (1 4 7 6

14 3 5 11 9

15 4 4 6 7

16 (1 1 1t 4

17 S 9 15 10

15 4 9 10

19 2 4 16 7

i0 4 3 13 ii

Iotmiis 51 91 217 183

x 2.33 4.55 10.35 9.15

ocular

abnormalitiies,

hypoplastic

or atretic

ear

canals,

males

with

cryptorchidism

and!

or penis

abnormality,

and

a high

incidence

of

digital

whorls

as

the

principle

findings.

The

17

reported

cases

are

summarized

in

Table

II

and

the

principle

findings

listed

in

Table

III. The

patient

described

in

this

paper

has

13 fully developed thoracic ribs and 13

nor-mal

thoracic

vertebrae. While this

combina-tion

of

anomalies

has

not

been

reported

previously, Destine, et al.6

called

attention

to one

patient

with

13 ribs

bilaterally

and

it

has since been determined that this child

also has an extra thoracic vertebrum. Ins-ley’s two I)atients had bilateral cervical

ribs and showed extensive anomalies of the

vertebral

column.

Extra

ribs

arc

not

un-usual in the population, but arc more often cervical or lumbar and not associated with extra vertebrae. It is possible that a review

(5)

previ-FIG. 4. Chest x-ray of J.B. Enlarged heart, 13 ribs, and 13 thoracic vertebrae are noted.

ously

reported

will

reveal

instances

of

this

dual

anomaly

that

were

overlooked.

The

reported

onset

of ankyosis

at age

14 months

in extension

of both

knees

defies

cx-planation.

Bracing

prior

to

onset

was

de-nied

by

the

mother.

The

deformities

have

not

responded

to

intensive

physiotherapy.

One

of Insley’ss

patients

tended

to assume

a

position

of partial

flexion

and

full

abduction

at the

hips.

In

all

latients

from

whom

data

was

ob-tamed,

an

increased frequency

of

fingertip

whorls

(

40 to

100%)

#{176}is noted. The

fre-quency in our case was 60%.

All

five

phenotypic

males

previously

(Ic-scribed

have

cryptorchidism

and/or

abnor-malitics

of

the

penis.

Our

patient

had

o The normal percentage of digital whorls is

(6)

v

____

13-15(D)

__________J

19-20(F)

#{163}*

A*

‘-

______

21-22(G)

‘-

_______

16-18(E)

xY

726 CHROMOSOvlE

lSq-DELETION

SYNDROME

‘-3(4)

si

4-5(B)

1ilc6)c71s

6-12(C)

*1

J

1I(;. 5. Karvotvpe vith ptrtial deletion of long arm of one clironlosome 18.

normal external gentalia with

‘el1-de-scended, clinically normal scrotal gonads.

A

highly

arched

palate

is

a well

knovn

feature

of

several

autosomal

syndromes,

in-eluding the 18q-. However, the striking

pig-rnentation

over

the

area

of the

hard

palate

in our patieIt is

apparently

a new

finding.

I

AJ

#{163}

.,.

;

:

1 I

16

.,.

17

18

lSq-.

Fic. 6. Partial karvotvixs

ltl)el((l E-tzroup (hronlosonles.

showing terniinallv

The

frequent

occurrence

of mid-face

dys-plasia, atretic or hypoplastic ear canals,

small

mandible,

and

impaired

hearing

mdi-cate abnormal development

of

structures

derived from, or closely associated with, the

first visceral arch. McKenzie1 has

sug-gested that similar anomalies affecting ar-eas of the face, ear, and palate are due to insufficiency of the stapedial artery during

the first 2 months of gestation and he

groups them as the First Arch syndrome.

Atresia

of

the

ear

canals

has

also

been

noted

in

two

of

four

patieiits

vith

an

18r

chromosome

and

all

four

of

these

patients

had

a high

frequency

of fingertip

whorls.4

Since the commonly accepted mechanism

of formation

of a ring

chromosonie

requires

deletions of the terminal portions of

both

the short and long arms, it is speculated

that

the genetic locus or loci that influence

development of the ear canals and middle

cars,

as well

as the

high

incidence

of (Iigital

whorls,

may

l)e located

near

the

ends

of the

long

arms

of

the

number

18 chromosomes.

h’

.

notes

that

this

hypothesis

is

supported by the irese1ce of nornial ear

(7)

TABLE

II

SUMMARY OF REPORTED FINDINGS IN 17 CASES OF PARTIAL DELECTION LONG ARM OF CHROMOSOME 18

Crypt

Reference GR M HE MR DR WI, 0.4 FF CM MFD It! SD and/or CUD II PA

1 + + + + + 50% + + + + + + female ? +

Mother 26. father 40 ; absent columella, high palate. eyes deep seated ; prominent chin. masses both buecal areas. brachycephaly; widely spaced nipples; horseshoe kidney ; third toe overlapped by fourth and second. edema of feet.

small masses lateral aspects feet; dimples dorsum of ha’irls. epitrochlear area and lateral aspects patellae; simian position thumbs, bilateral simian lines, absent fiexion crease left fifth finger; absent labiae minora.

2 Casel + + + + + 40% ? + ? + ? + + ? ?

Mother 22, father 25 ; tower skull, prominent forehead and chin, high palate; eyes deep seated, hypertelorism,

anti-mongoloid slant; widely spaced nippleE dimples on hands, simian position of thumbs, web between third and fourth fingers left, clinomlactyly fifth fingers; genu valgum, flat feet, small masses lateral aspects both feet; “Jacksonian” seizures.

Case2 + + + + + 90% + + ? + + + female + + Mother 33, father SI; tower skull, nuchal area flat and broad, prominent malar areas and chin, small masses buccal areas, broad nasal root ;cleft palate; microcornea. unilateral glaucoma and absent anterior chamber, corneal opacity; simian

position of thumbs, dimples dorsum of hands, x-rays show “bouchon de champagne” shape second phalanges, bilateral simian lines; third and fourth toes overlapped by second and fifth.

S Casel’ + + + + ? 80% + ? ? + + ? ? + ?

Case2 + + + + ? 50% + ? ? + + ? ? + ?

CaseS’ + + + + ? 70% + ? ? 0 + P ? 0 :

Case4 + + + + ? 70% + ? ? + + ? ? + ?

18 Casel ? ? ? ? ? ? + ? ? P ? ? ? ? +

Case 2 ? ? P ? ? ? + ? ? ? ? ? female ? +

Patients were siblings; mother’s karyotype showed partial deletion of the long arm (Sf a number 18 chromosome with

translocation of the (leleted material to tIme short arm of a G group chromosome.

S Casel + + 0 + + 60% + ? + 0 0 + + 0 0

Mother 20. father 23; skull bones soft; epicanthiic folds; fingers clenched, left index overlapped middle finger. unilateral

simian line; edema of feet. right second toe overlapped third; bilateral cervical ribs; exostosis right tibia; bilateral

talipes equinovarus.

Case2 + + 0 + + 60% ? + + ? 0 ? + + 0

Mother 25, father 30; plagiocephaly; eyes deep seated with mongoloid slant; prominent upper lip; double ante-cubital flexion creases; small hands; feet small and edematous, second toes dorsally placed; tended to lie with hips partially

flexed and fully abducted; femora slender with coxa s-alga; bilateral cervical ribs, other ribs slender and irregular with the right twelfths rib smaller than the left; multiple vertebral anomalies.

6 Case I 0 ? + ? + 60% + P ? ? 0 ? female 0 7

Mother 40, father 45; mask-like. elongated face; hypertelorism, epicanthus; highly arched palate, dental malocclusion, atd. angle 60#{176}on right, 35#{176}on left; third toes overlapped by second and fourth; pubic hair and breast development age 10.

Case 2 + + + 7 + 100% + + + ? P ? female 0

Mother 32, father 37; epicanthus with mongoloid slant, anomalies of macula; cleft lip; dimples on hands and fingers;

fat pad dorsum of feet, third toes overlapped by fourths; 13 ribs bilaterally.

9 7 + + 7 + ? + + + 7 ? + + 7 7

Mother 33, father 26; mother with positive treponemal-immob. test; large fontanehles; multiple skin folds of neck; widely

spaced nipples; umbilical hernia; hands held in claw position, dystrophic nails; bilateral tahipes calcaneovalgus.

19 + 0 + 7 ? 7 + + + + 0 + female ? +

Mother 25, father 27; wide fontanehles; broad nasal bridges; epicanthal folds; hypoplastk’ ear canals; dimples over knuckles, talipes equinovarus.

5 + + + + + 50% 0 + ? + + ? + + +

Mother 53; thin nose and nostrils; cleft palate; micrognathism; hypoplastic ear canals; retarded bone age; atd. angle less than 300 bilaterally.

Curran + 0 + + + 60% 0 + + + + 0 0 + 0

Mother 23, father 2t; highly arched, pigmented palate; simian position of thumbs, bilateral simian lines; third toes

overlapped by fourth; anklyosis of knee joints; 13 thoracic ribs and 13 thoracic vertebrae; circumscribed area depigmented

hair occipital region.

+=present 0 =absent ?=not mentioned GR=growths retardation M =microcephialy HE =hypertrophy of ear parts MR = mental

retardation DR =developmental retardation Wh =fingertipwhorls OA =ocular abnormality FF =fusiform fingers CM =carp mouth HFD =mid-face dysplasia HI =impaired hearing and/or hypoplastic ear canals SI) =sub-acromial (limples Crypt. and/or PA

(8)

7h;.5t 76.5% 76.5% 76.5% 70.6% 64.7 58.8% 5 .9r; 5 . 47 .o;; 41 .!% 4l.’% 41 35.3% 35.3%

c9 .4(;;

83.3/; of Illales

728 CHROMOSOME

18q-DELETION

SYNDROME

TABLE

III

CUMULATIVE PERCENT INCIDENCE OF PIIINCI pr;

FINDINGS REPORTED IN 17 CASES OF 1’AIITIAL

DELETION OF TILE LONG .1(MS

OF C1IRoIosoIE 17--IS

Growth failure

Ilypertropily of external ear l)arts high incidence of digital whorls Ocular abnormalities

Microceplialy Mental retardation

l)eveiopnsental retardation

Fusiforlu fingers

l1 i(l-face dvsplasia

Ilypopiastic ear canals and/or

iIn1)aired hearing

CILq nIOUtIL

Congenital heart (lisease 3rd toe overlapped by 4th

an(i/or 2I1(l

Sub-acromial dimples

Ilypotonia

Cryptorehidislll LIS(l br penis al)normaiity

the

short

arm

of

a

number

18 autosome.

While

it is difficult

to determine

where

nor-mal

ends

and

hypoplasia

begins,

it was

felt

that

our

patient

had

unusually

narrow

ear

canals.

It

was

the

opinion

of

all

examiners

that

J.B.’s congenital heart lesion was an atrial

septal

defect

(

secundum

)

.

This

was

con-firmed

by

angiocardiography.

The

cardiac

anomaly was felt to be asymptomatic and

not

a

contributing

factor

to

tile

severe

growth

and

developmental

failure.

DISCUSSION

OF

AUTORADIOGRAPHIC

DATA

Giannelli

and

Howlett

showed

that

the

E-group

chromosomes

may

be

identified

through

comparison

of their

“morphological

index”

and

terminal

labelling

data.

They

obtained

the

morphologic

index

by

dividing

the

arm

ratio

of

each

chromosome

into

its

total

length.

They

found

chromosome

16 had

a high

index

and

heavy

label,

chromo-some

17 had

an

intermediate

index

and

light

label,

and

chromosome

18 had

a low

index

and

a heavy

label.

In

the

present

case

the

chromosomes

16 had

normal

morphology

and

were

heavily

labelled

(

Fig.

6)

.

When

grain

counts

were

ranked over the four

chromosomes

17 and

18, the deleted chromosome was one

of the

two

most

heavily

labelled

chromosomes

in

19 of 20

cells

and

was

identified

as an

lSq-chromosome

(

Table

I

)

.

Terminal

labelling

has previously been used to identify the

de-leted

chromosome

of two

46,18q-

patients.17

In

other

presumptive

46,18q-cases,

the

de-leted

chromosome

has

only

been

identified

morphologically.25O1Sm9

SUMMARY

A patient

with

partial

deletion

of the

long

arm

of

a single

number

18 autosome

is

de-scribed.

He

presents

many

of

the

somatic

abnormalities previously described, though

lacking genital anomalies. The most

com-mon

stigmata have been mental

retarda-tion,

growth

and

developmental

failure,

mi-crocephaly, hypertrophy of ear parts, ocular

al)normalities,

a high

incidence

of

fingertip

whorls, fusiform fingers, mid-face dysplasia,

and

hypoplastic

ear

canals.

REFERENCES

1. Do Grouchy,

J.,

Rover

P.,

Salmon,

C.,

and

Lang,

M.

: D#{233}l#{233}tionpartielle des bras longs

du chromosome 18. Path. Biol., 12:579,

1964.

2. Lejeune,

J.,

Berger,

R.,

Lafourcade,

J.,

and Rethore, M. : La d#{233}l#{233}tionpartielle du bras long du chromosome 18. Individualisation d’un nouvel #{233}tatmorbide. Ann. Genet., 9:32, 1966.

3. Wertelecki, W., Schindler, A. NI., and Gerald, P. S. : Partial deletion of chromosome 18. Lancet, 2:641, 1966.

4. Lafourcade,

J., and

Lejeune,

J.

: La deficience clue bras long d’un chromosome 18

(

18q-), Un. Med. Canada, 97:936, 1968.

5. Kushnick, T., and Matsushita, C. : Partial dele-tion of long arms of chroniosome 18.

PEDI-ATRICS, 42:194, 1968.

6. Destine, M. L., Punnett F!. H., Thovichit, S., DiGeorge, A. M., and Weiss, L. : La

d#{233}l#{233}-tion partielle du bras long du chromosome

18 (syndrome 18q-). Rapport de deux cas.

(9)

729

7. Punnett,

H. H. : Personal

communication,

1969.

8. Insley,

J.

: Syndrome associated with a defi-ciency of part of the long arm of

chromo-some

no

18. Arch. Dis. Child., 42:140, 1967

9. Day, E.

J.,

Marshall, R., Macdonald, P. A. C., and Davidson, W. M. : Deleted chromosome 18 with paternal mosaicism. Lancet, 2:1307, 1967.

10. McKenzie, J.:

The

First Arch syndrome. Arch. Dis. Child., 33:477, 1958.

11. Wang,

H. C.,

Melnyk,

J.,

McDonald,

L. T.,

Uchida, I. A., Carr, D. H., and Goldberg, B.: Ring chromosomes in human beings. Nature,

195:733,

1962.

12. Genest, P., Leclerc, R., and Auger, C. : Ring

chromosomes and partial translocation in the

same cell. Lancet, 1 : 1426, 1963.

13. Lucas, M., Kemp, N. H., Ellis, J.

R., and

Mar-shall, R. : A small autosomal ring chromo-some in a female infant with congenital

mal-formations. Ann. Hum. Genet., 27:189,

1963.

14. De Grouchy, J., Leveque, B., Debauchez, C.,

Lamy, M., and Marie, J.: Chromosome

17-18 en anneau et malformations cong#{233}nitales chez une file. Ann. Genet. 7: 17, 1964.

15. De Grouchy,

J.: Chromosome 18: A topologic

approach.

J. Pediat., 66:414, 1965. 16. Giannelli, F., and Howlett, R. M. : The

identifi-cation of the chromosomes of the E-group

(

16-18 Denver) : An autoradiographic and

measurement study. Cytogenetics, 6:420,

1967.

17. Reinwein, H., Gorman, L. Z., and Wolf, U.:

Defizienz

am langen

Ann

eines Chromosoms

Nr. 18 (46,XX18q-).

Z. Kinderheilk.,

101:

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18. Law, E. M., and Masterson,

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Acknowledgments

We

are indebted to Drs. Dorothy Warburton and

Cyril

A. L.

Abrams, College of Physicians and Surgeons of Columbia University, for their advice and assistance; to Dr. Felix Kavanagh, Jersey City Medical Center, for assistance with translations

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1970;46;721

Pediatrics

John P. Curran, Farouk L. Al-Salihi and P. W. Allderdice

PARTIAL DELETION OF THE LONG ARM OF CHROMOSOME E-18

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