`Typus Edinburgensis' Explained

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‘Typus

Edinburgensis’

Explained

In 1974, an Edinburgh family was described in

which five infants from three generations had a

consistently abnormal facial appearance, retarded

motor and mental development, and failure to

thrive. All died in the first months of life. The

eponym “Typus Edinbungensis” was used to label these infants.’ Although at that time no chnomo-somal abnormality was detected, it was predicted that the advancement of cytogenetic technology might eventually reveal an associated chnomosomal abnormality. High-resolution chromosome analysis

has now identified a familial reciprocal and

appan-ently balanced translocation between chromosomes

1

and 2 in three members of this family, following

detection of an unbalanced kanyotype in a neonate

with an abnormal phenotype similar to that previ-ously described. This infant is the subject of the

present report.

CASE REPORT

A 17-year-old married primigravid woman with no

significant past medical history was delivered at full term

of a female neonate (Fig 1, A) weighing 3.24 kg. The child

had a head circumference of 37 cm (87th centile), with

parietal bossing. She had long black silky hair, low-set

mishapen ears, small eyes, a long philtrum and

carp-shaped mouth, asymmetric hypomandibulosis, a small

beaked nose, flexed upper limbs and extended lower

limbs, long slender fingers and toes, a moderately

high-pitched cry, and mild stridor. Laryngoscopy revealed a

small, proportional larynx and an intact palate. A chest

roentgenogram showed 1 1 pairs of broad irregular ribs

flattened anteriorly. Skeletal survey demonstrated no

other abnormality, and bone age was 2 months ± 2.8

months (mean ± SD). Ultrasonography of the head and

abdomen were normal during the neonatal period. The infant failed to thrive; feeding difficulties and

vomiting led to a diagnosis of pyloric stenosis, which

responded to pyloromyotomy at 6 weeks ofage. Recurrent

chest infections required hospital treatment with

intra-venous antibiotics and physiotherapy. Sweat tests,

plasma immunoglobulin, and T and B lymphocyte

func-tions were all normal. Contrast examination

demon-strated incoordination of swallowing, aspiration of fluid

into the lungs, and mild gastroesophageal reflux. Despite

these problems, weight and length continued to increase

along the 3rd centile.

At 16 months she showed developmental delay, per-forming at a mean level of 8 months. She had an ataxic cerebral palsy, with hypotonia and severe scoliosis. Com-puted tomography of the brain demonstrated generalized cerebral atrophy with widening of the sulci and moderate dilation of the ventricles. At 26 months of age she re-mained severely developmentally delayed and died from an overwhelming pneumonia. Autopsy examination was not carried out.

CYTOGENETIC INVESTIGATIONS

Cytogenetic evaluation of peripheral blood

lympho-cytes was carried out during the neonatal period using a

modification of the method of Yunis’ for high-resolution banding. The affected child (V-i, Fig 2) was found to

Received for publication Sep 4, 1990; accepted Oct 12, 1990. Reprint requests to (I.A.L.) Neonatal Unit, Simpson Memorial Maternity Pavilion, Lauriston Place, Edinburgh, Scotland.

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KEY

0 male

0

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suspected carrier

#{174}

confirmed carrier

fi’

clinical case described by Habel

.

confirmed case spontaneous abortion

N termination of pregnancy

152

PEDIATRICS

vol.

88 No. 1 July 1991

have an unbalanced karyotype with an abnormality of

the long arm of chromosome 2 (2q37.i-*qter) in all 50 cells examined (Fig 3). The karyotype of the father was

normal but the child’s mother (IV-3) was found to carry

a small, apparently balanced reciprocal translocation (Fig 3) involving the distal segments of the long arms of

chromosomes i and 2: 46,XX,t(i;2)(q42.3;q37.i). Hence

the child described here represents the unbalanced prod-uct of a balanced translocation segregating in the mother.

The child’s karyotype is, therefore, 46,XX-2,+der(2),t(1;2)

(q42.3;q37.i)mat.

In light of this finding, chromosome analysis was

un-dertaken on all available family members, and the

ma-ternal grandfather (111-7) of the affected child was shown

to carry the same balanced translocation as his daughter;

his karyotype, therefore, is 46,XY,t(i;2)(q42.3;q37.i). A

maternal great aunt (111-3) was also identified as a carrier

while other family members (111-8 to III-i2 and

IV-iO---14) were shown to have normal karyotypes.

DISCUSSION

In i974 Habel’ described an Edinburgh family in

which five infants fnom three generations had a

consistent, dysmorphic appearance and died in the first months oflife. Because of superficial similarity

to “Typus Amstelodamensis,” the term coined by

Connelia de Lange to label infants with Bnachmann

de Lange Syndrome,3 Habel coined the description

I

II

Ill

Iv

v

“Typus Edinbungensis” for what appeared to be a new syndrome. He commented that the frequency of the occurrence of the syndrome was “best ex-plained by the inheritance of a chromosome abnon-mality sub-microscopic in type and therefore

un-detected by present day methods of analysis.”

Subsequent to Habel’s report, the mother of the original propositus had two spontaneous abortions

at iG weeks and a normal daughter. She also had a

stillbirth at 30 weeks’ gestation, this being a

mac-enated male fetus with a large head, advanced bone

age, a right club foot, and a single palmar crease on the left hand. Chromosome analysis of cultured fetal tissue was unsuccessful.

The present case report describes the first child (V-i) of the oldest sibling (IV-3) of the infant (IV-4) described by Habel (Fig. i, B). Cytogenetic analy-sis of V-i identified an unbalanced karyotype

re-sulting from malsegregation of a familial reciprocal

translocation between chromosomes i and 2. The unbalanced karyotype observed in this child is con-sequent upon 2:2 disjunction and subsequent

adja-cent-i segregation in the mother (IV-3). There is a

striking similarity in phenotype between the af-fected child and the five infants from the same family previously described by Habel, providing circumstantial evidence for the transmission of the

Fig 2. Pedigree of family, expanded from previous report in i974.’

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2

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2

1. Habel A, ‘Typus Edinburgensis’ Pediatrics. 1974;53:425-530 2. Yunis JJ. High resolution banding of human chromosomes.

Science. 1976;191:1268-1270

3. de Lange C. Sur un type nouveau de generation (typus

Am-stelodamensis). Arch Med Enfant. 1933;36:713

4. Young RS, Shapiro SD, Hansen KL, Hine LK, Rainosek DE,

Guerra FA. Deletion 2q: two new cases with karyotypes

46,XY,del(2)(q32q33) and 46,XXdel(2)(q36). J Med Genet. 1983;20:199-202

5. Sanchez JM, Pantano AM. A case of deletion 2q35-qter and

a peculiar phenotype. J Med Genet. 1984;21:147-149

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Fig 3. (a) Partial karyotype of IV-3 (mother) showing balanced reciprocal translocation between chromosomes 1 and 2. (b) Partial karyotype of V-i (proband) showing derivative chromosome 2. (c) Idiogram showing

break-points. Breakpoints are indicated by arrows. Derivative

chromosomes on right.

translocation through several generations of this

family. It seems likely that only one type of imbal-ance has occurred in these infants, namely partial tnisomy iq with associated partial monosomy 2q.

Partial monosomy for the long arm of chromosome

2 has been described only rarely.4’5 In these cases the deletion occurred de novo and there were no reports of similar phenotypic abnormalities in the families. In contrast to Typus Edinburgensis, the infants were growth retarded and microcephalic at birth and the clinical descriptions do not resemble the present case non the others in the Edinburgh family.

A syndrome of partial tnisomy iq has been

de-scnibed,6’7 with phenotypic featunes including

ma-crocephaly, prominent forehead, large fontanelle, flat nasal bridge, micnognathia, low-set malformed ears, facial capillary nevi, and cardiac defects. Var-ious of these features are described in the present

case and in the five other members of the family described by Habel. Thus Typus Edinburgensis can

be explained as tnisomy iq42.3-*.qter modified by

loss of 2q37.i-*qter.

Identification of this translocation has enabled

us to test many of the surviving members of the family, thus eliminating anxiety in those with a normal kanyotype, and allowing counseling of phe-notypically normal balanced translocation carriers. In predicting the prospective risk for reciprocal tnanslocation carriers, Stene and Stengel-Rutkowski8 demonstrated a high risk for unbalanced offspring if the chromosomal imbalance was relatively small and could occur through a common disjunction/segre-gation mechanism. This appears to be the case in the present family, which has shown an apparent high risk for unbalanced offspring. Indeed the mother (IV-3) of the child described has subse-quently had another pregnancy terminated at 18 weeks’ gestation, after amniocentesis demonstrated a male fetus karyotype 46,XY,-2,+der(2),t(i;2)

(q42.3;q37.1)mat. Although the abortus was

macer-ated, hypertelonism, hypomandibularism, campto-dactyly, and a secundum type atnial septal defect were identified.

Since this manuscript was submitted for

publica-tion, the mother (IV-3) of the child described has

had another termination because of the identifica-tion again by chonionic villous biopsy of a fetus with Typus Edinburgensis.

I. A. LAING, MA, MBCHB, FRCPE

E. G. H. LYALL, BSC, MBCHB, MRCP

L. M. HENDRY, BSC, PHD, DIC

P. M. ELLIS, MSC, DIPRCPATH

Dept of Child Life and Health, University of

Edinburgh

Neonatal Unit, Simpson Memorial Maternity Pavilion

Lothian Area Cytogenetics Laboratory, Royal

Hospital for Sick Children Edinburgh, Scotland

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154

PEDIATRICS

vol. 88 No. 1 July 1991

6. Michels VV, Berseith CL, O’Brien FJ, Dewald G. Duplication

of part of chromosome lq: clinical report and review of literature. Am J Med Genet. 1984;18:125-134

7. Chia NL, Bousfield LR, Poon CCS, Trudinger B. Trisomy (lq)(q42-.qter): confirmation of a syndrome. Clin Genet.

1988;34:224-229

8. Stene J, Stengel-Rutkowski S. Genetic risks for familial,

reciprocal translocations with special emphasis on those lead-ing to 9p, lop and 12 trisomies. Ann Hum Genet.

1982;46:41-74

Group

A $-Hemolytic

Streptococcal

Balanitis:

It May Be More

Common

Than

You Think

Group A $-hemolytic Streptococcus (GABHS) is

a common pathogen in pediatrics. Its role in

impe-tigo and pharyngitis is well known. Recent pediatric

literature has documented GABHS as a cause of

vulvovaginitis and penianal disease.”2 However, its

role in the evaluation of a prepubertal, uncircum-cised male with a penile discharge and balanitis has

not been well documented in the pediatric

litera-tune. We report two cases of balanitis caused by

GABHS in prepubertal males.

CASE REPORTS

Case 1

A 6#{189}-year-old uncircumcised boy presented with a

i-month history of a yellow-brown penile discharge. The child reported some mild discomfort at the onset of

symptoms, but no swelling or erythema was noted. The

foreskin was retractable by report, and the discharge

cleared with bathing. No trauma or other signs of physical abuse were reported. One month prior to this visit, how-ever, the patient was upset, but “couldn’t tell his parents why.” Since then, the patient had been fine, and no changes in behavior had been observed. During the time

of the discharge, no diarrhea, urinary frequency, or

dysuria was noted. Interviews of both the patient and

parents alone indicated no history suggestive of sexual abuse. The patient had a short history of coryza, vomit-ing, diarrhea, and a transient tactile fever 2 weeks prior to evaluation, all of which had resolved. He was currently receiving no medication.

At the time of physical examination, the patient was afebnile. He had a clear, crusty nasal discharge, and his pharynx was clear. The remainder of his examination was unremarkable except for his genitalia. The foreskin

was mildly swollen and erythematous; the patient only allowed partial retraction of the foreskin. A creamy, yellow discharge was present, and the glans and meatus could not be visualized. His rectal tone was normal, and he had no bruises or other signs of abuse or neglect.

Cultures for Neisseria gonorrhoeae and Chiamydia, a wet preparation for Trichomono.s, and cultures for

enter-ics and GABHS were obtained. A Gram stain of the

discharge showed moderate Gram-positive cocci in pairs and chains. All studies were negative except for heavy growth of GABHS. The patient was treated with a iO-day course of amoxicillin; he was seen in follow-up 3 weeks later, and his discharge had resolved. Proper

fore-skin care was reinforced at that time. Two months later,

the patient was seen for recurrent symptoms. Cultures positive for GABHS were obtained from underneath the foreskin and the oropharynx. He was successfully treated with a 10-day course of cephalexin.

No other recurrences have been noted.

Case 2

A 4#{189}-year-old uncircumcised boy was evaluated for a swollen, irritated foreskin of 24 hours’ duration. The parents commented that routine hygiene was difficult, and he “frequently had his hands in his genital area.” No local pain or dysuria was noted, and the patient was reported otherwise to be in good health. Two weeks earlier, otitis media and scarlet fever (culture positive for

GABHS) had been diagnosed. He had a good clinical

response to a iO-day course of amoxicillin. Three days after he completed the amoxicillin, the foreskin irritation

was noted. His review of systems and past medical history

were unremarkable.

At the time of physical examination, the patient was afebrile. Examination revealed an erythematous, swollen, nontender foreskin which was retractable. The underside

of the retracted foreskin as well as the glans were

ery-thematous with a moist, glistening, raw appearance. A thin, clear, and colorless discharge was present.

Balanitis was diagnosed, and the father was instructed

on proper foreskin hygiene. A culture of the discharge

was positive for GABHS. Cephalexin therapy was started. He was noted by telephone follow-up to be free of

symp-toms by day 3 of a 10-day course.

No recurrences have been noted.

Received for publication Jun 18, 1990; accepted Aug 28, 1990.

Reprint requests to (C.L.C.) The George Washington University Medical Center, Dept of Pediatrics and Health Care Sciences,

2150 Pennsylvania Aye, NW, Washington, DC 20037.

American Academy of Pediatrics.

DISCUSSION

Major pediatric texts list balanitis in prepubertal

males as being caused by improper hygiene or local

irritation,3 on they do not discuss it at all.46 In

Breese and Hall’s Beta-Hemolytic Streptococcal

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1991;88;151

Pediatrics

I. A. LAING, E. G. H. LYALL, L. M. HENDRY and P. M. ELLIS

`Typus Edinburgensis' Explained

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1991;88;151

Pediatrics

I. A. LAING, E. G. H. LYALL, L. M. HENDRY and P. M. ELLIS

`Typus Edinburgensis' Explained

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