three more ‘happy puppets’
TRANSCRIPT
Develop. Med. Child Neurol. 1973, 15, 63-74
Case Reports
Three More ‘Happy Puppets’ Oliver Mayo” Matilda M. Nelson7 H. R. A. Townsend
Introduction The exact delineation of a particular
syndrome associated with severe mental retardation is often difficult because only rare individual cases may be recognised.
Western General Hospital, Edinburgh. * Present address: Waite Agricultural Research
Institute, University of Adelaide, Glen Osmond, South Australia 5064.
Present address: Department of Human Genetics, Medical School, University of Cape Town, Box 594, Cape Town, South Africa.
Reprint requests to Dr. M. M. Nelson.
I Physical features
Facial appearance Blue eyes Choroidal defect Protruding jaw Protruding tongue Microcephaly Occipital depression
OFC (crn) Severe mental retardation
Spasms and fits Frequent laughter
Gait I Jerky arm move-
Hypotonia Dermatoglyphics
ments
Chromosomes
EEG
Three cases of ‘puppet’ children were reported by Angelman in 1965, and two years later two further cases were reported by Bower and Jeavons. A sixth case was added by Berg and Pakulza in 1972.
During visits to local hospitals for mentally retarded children we saw two children whom we thought would merit further study as possible examples of the ‘happy puppet’ syndrome, and we have since seen a third case at the Genetic Counselling Clinic. We present here the
TABLE I Comparison of physical features in nine cases
Angelman
1 2 3
+ + + + + + + + + + + + + +
44.4 45.1
+ + + + + + stands ataxic iolding-
on + + + t ?
46/XX 46/XX
+ +
+ + + f + + +
45.6
+ + + ataxic
+ + ?
46/XY
+
Bower and Jeavons
1 2
+ + + + + + + + + + + + + -
51.0 46.0
+ + + + + + staxic ataxic
+ + + ? ? ?
16/XX ?
+ + (male)
- ?erg an1 Pakulz
1
+ + + + + +
44.8
+ 4 +
ataxic
+ + N
-
-
46/XX
+ -
Present report
1 2 3
+ + + + + + + + ic + + + + + + + +
44.5 43.5 47.0
+ + + + i- + (smiling) (smiling
unable unable unable .o walk to walk to walk
+ + + +
owAB ? extra ridge whorls
- -
- -
+ It. ?.
- -
count 46/XX 46/XX 46/XY
+ + + 63
DEVELOPMENTAL MEDICINE A N D CHILD NEUROLOGY. 1973, 15
Angelman
1 2 3
Bower and Berg and Jeavons Pakulza Present report
1 2 1 1 2 3
Age of examina-
Delivery Gestation Birth weight (g)
tion (years)
Age at which smiled (months) I ? ? ? 1 4 t 4 l ? / 3
5 10/12 6 10/12 9 6/12 7 7 sf. 54 normal ? normal normal normal normal normal
? ? ? term term term 44/52 2350 2950 2830 3968 4053 3345 2970
Age sat without- support
Age walked (years) Age talked Ageofonset offits Family history
Siblings
2 normal 40/52 2960
2
1 yr+
19/12 negative
- -
-
2yrs 2yrsf 2yrs+ 9 mos 10mos ? 1 yr+
1 6/12 3 2 6/12 10/12 1 10/12 2 1 negative negative negative nega- nega- negative negative
10 2 2 ~ ( N N D , * 3 l(grand 2 (1 Down’s cerebral ma1 syndrome) birth seizure)
injury)
- ? 2 4 - - - - - 5 6
- - -
tive tive
2 9/12 normal 36/52 2960
1) - - - 1
negative
2
*NND = neonatal death.
case reports and the electroencephalo- graphic findings of these three children. Their main features and those of the other six published cases are summarised in Tables I and 11. The electroencephalogram (EEG) reports are summarised in Table 111.
Case Reports CASE 1 (R.M.)
R.M. is the youngest of three children of normal, unrelated parents and there is no history of mental retardation in either family.
Apart from a short period at the age of seven days when grunting respirations and minor feeding difficulties were noted, this girl’s early progress was unremarkable. The pregnancy had been normal. By the age of one year, both physical and mental retardation were obvious and it was then that she started to have fits. Myoclonic jerks were described at this time.
At the age of two years eight months she was investigated in the Royal Hospital for Sick Child- ren, Edinburgh (Dr. T. T. S. Ingram). All tests gave results which were within normal limits, except for the developmental tests and the EEG (see below). Phenytoin and primidone, with pyridoxine supplements, were used to control the fits.
At five years six months she was admitted to the
Western General Hospital (Professor A. E. H. Emery) for re-evaluation. On examination she was seen to be a fair-haired, blue-eyed, microcephalic, mentally retarded child with a peculiar facies (Fig. 1). The nose was hooked and the mandible protruded so that the mandibular teeth overlapped the maxillary. She had frequent outbursts of giggling and laughing, without provocation. Her movements were erratic, jerky and almost con- tinuous. She was able to sit and kneel, but could not stand or walk. She constantly chewed objects. Sight and hearing appeared to be normal, but there was a left divergent strabismus (Dr. G. Dhillon). Fundi were normal. Full investigation gave normal results.
CASE 2 (E.L., Fig. 2)
E.L. is the only child of normal, unrelated parents and there is no family history of mental retardation.
This girl’s early progress appeared to be normal, but at 10 months it became obvious that her development was delayed. During pregnancy, her mother had taken four ‘travel-sickness’ tablets a t eight weeks and had been in contact with rubella infection at about 12 weeks. No other possible contributory factor was noted.
At one year five months this child also was investigated in the Royal Hospital for Sick Children (Dr. T. T. S. Ingram) and was found to be functioning only at a five to six months’ age-level.
64
CASE REPORTS
Fig. 1. Case 1.
Her eyes were noted to be in continual movement but her vision appeared to be good. Fundus examination showed adequate pigmentation only in the macular area.
At two years she was seen in Professor Emery’s Genetic Clinic. The only new feature in addition to the above history was that during the previous three months she had developed attacks of twitching, without loss of consciousness or clonic movements. She was seen to be a fair-haired, blue- eyed, microcephalic child with a slightly beaked nose, a short upper lip and mild epicanthus. She sat steadily but made no attempt to stand. She played only momentarily with objects and had continuous jerky movements. She smiled con- tinually and grimaced, but did not have outbursts of laughter. Her tongue constantly protruded. She could see and hear, but made no attempts to vocalise.
CASE 3 (A.M., Fig. 3) A.M. was the second of three children of normal,
unrelated parents and there was no history of mental retardation in other members of either family.
This boy was born four weeks early (by dates), but had an unremarkabIe neonatal history except for some feeding difficulties. At the age of one year he was noted to be mentally and physically retarded.
At one year seven months he was investigated in the Royal Hospital for Sick Children (Dr. D. M. Douglas). All investigations were negative, except the EEG. A tentative diagnosis of the ‘happy puppet’ syndrome was discarded for lack of confirmation.
At two years nine months he was admitted to the Western General Hospital (Professor Emery). He &as then noted to be a fair-haired, blue-eyed, microcephalic child with a small, beaked nose, a short upper lip and a slight epicanthus. He could not sit without support. He smiled continually but did not laugh unless stimulated, when the response was excessive. His movements were jerky and continuous and his only play was to chew objects. Sight and hearing were normal. All other invest- igations, with the exception of the EEG, gave normal results.
EEG Reports CASE 1 (R.M.)
Age two yeurs: ‘hypsarrhythmia’. Age five years six months: mainly 3 to 4Hz large amplitude slow waves. Spikes were associated with these waves and they occurred as both generalised episodes and occipital runs. An occasional large generalised
E 65
TABLE
I11
EEG
rec
ords
in n
ine Cases
Age
@
ears
)
1+
2+
3+
5+
6f
7
Ange
lman
1 2
3
Hig
h am
pli-
tude
3-4
Hz
sym
met
rical
(1
5 m
onth
s)
Poly
spi
ke,
spik
e an
d N
ave
activ
ity
!n bu
rsts
J3
year
s)
Hig
h am
pli-
tude
occ
ipita
l pa
rieta
l spi
ke
disc
harg
es,
sym
met
rical
Spik
es a
nd
paro
xysm
al,
asym
met
rical
(3 r
ears
)
(5 y
ears
)
Bila
tera
l at
ypic
al s
pike
an
d w
ave
in
all a
reas
(2
3 ye
ars)
Alm
ost c
on-
tinuo
us s
pike
an
d w
ave,
po
lysp
ike a
nd
wav
e (6
yea
rs)
Bow
er a
nd J
euvo
ns
1 2
~
Hig
h vo
ltage
H
igh
volta
ge
2-3H
z w
aves
5H
z sy
m-
and
spik
es
met
rical
su
perim
pose
d (2
0 m
onth
s)
on 5-
6 H
z (1
3 m
onth
s)
Spik
e an
d H
igh
volta
ge
wav
e ac
tivity
, 2.
5-3H
z w
ith
mai
nly
at
occi
pita
l 2H
z sp
ikes
(2
yea
rs)
Del
ta rh
ythm
no
spi
ke
(23
year
s)
Spik
e and
C
ontin
uous
w
ave
activ
ity,
2%
spik
e m
ainl
y at
an
d w
ave
2Hz
(43
year
s)
Spik
e an
d w
ave a
ctiv
ity,
mai
nly
at
ZHz
Zont
inuo
us
Alm
ost c
on-
iync
hron
ous
tinuo
us 2
Hz
iym
met
rical
sp
ike
and
5-6H
z w
ave
'I ye
ars)
(7
yea
rs)
Ber
g an
d Pu
kulz
u
1
Freq
uent
sp
ike o
r sho
rt
wav
e di
scha
rges
(3
yea
rs)
Hig
h am
pli-
tude
slo
w
wav
es a
nd
spik
es
(5 y
ears
)
Gen
eral
ised
ex
cess
of
slow
activ
ity
(6f
year
s)
Pres
ent
repo
rt
1 2
3
Larg
e am
pli-
tude
29
Hz
w
aves
with
sm
all s
pike
s (1
7 m
onth
s)
Larg
e am
pli-
tude
2f-
4Hz
wav
es w
ith
smal
l spi
kes,
al
so 5
-6H
z at
50
-1W
pV
(2&
year
s)
Larg
e am
pli-
tude
slo
w
wav
es, 3
4H
z sp
ikes
pres
ent,
gene
ral a
nd
occi
pita
l
Mor
e co
n-
tinuo
us o
cci-
pita
l act
ivity
, ot
herw
ise
unch
ange
d (6
% ye
ars)
(53
year
s)
Larg
e am
pli-
tude
5H
z wit1
sl
ow c
ompo
- ne
nts a
t 2-3
H
with
sm
all
spik
es
(14
mon
ths)
Dom
inan
t
rhyt
hm w
ith
34
Hz
delta
ac
tivity
po
ster
iorly
. La
rge
ampl
i- tu
de 3
Hz
wav
es w
ith
shar
p w
aves
oc
cipi
tally
Dom
inan
t 6H
z rh
ythm
s w
ith il
l- de
fined
spi
ke
wav
e co
rn-
plex
es
(3
year
s)
6-7H
z e
(2%
year
s)
CASE REPORTS
Fig. 2.
spike was also seen. Age six years nine months: almost identical with previous EEG. Less genera- lised episodic spike and wave activity but more continuous occipital activity.
CASE 2 (E.L.)
Age one year five months: the record was dominated by large amplitude 2g to 4Hz waves in all regions, with amplitude up to 300pV at times. These waves were sometimes associated with small spike potentials. As the child became drowsy, the frequency of the waves decreased slightly towards 2Hz and the amplitude increased even further.
Age two years three months: again, the most prominent feature was large amplitude 24 to 4Hz waves occurring in all regions, with amplitude up to 300pV. These were frequently associated with small
Case 2.
spike potentials and occurred in runs, sometimes anterior, sometimes central, sometimes posterior. There was no gross asymmetry. 5 to 6Hz rhythms at 50 to lOOpV were also a prominent feature, mostly posterior in distribution and seen at those times when the slow waves temporarily ceased.
CASE 3 (A.M.)
Age one year two months: runs of large amplitude 200 to 300 5Hz rhythms with slower components at 2 to 3Hz and occasional intermixed small spikes. Second EEG, two days later: 4 to 5Hz rhythms up to 300pV. Occasional episodes of bilateral theta activity.
Age two years nine months: dominant 6 to 7Hz theta rhythm symmetrical with intermixed 3 to
Fig. 3. Case 3.
67
DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1973, 15
4Hz delta activity posteriorly. Several runs of 3Hz occipital deltaactivity of large amplitude (> 200pV) with intermixed sharp waves.
Age fhree years rwo months: dominant 6Hz rhythms with runs of ill-defined occipital spike wave complexes, often occurring independently on the left and right sides.
Discussion The similarities between the six previ-
ously published cases and the three presented here are emphasised in Tables I and 11. Two of our three cases were younger at the time of diagnosis than those in other reports, which may account for some variation in details-such as the absence of a protruding jaw. Perhaps the most outstanding difference is in the hypotonia: Berg and Pakulza’s case is reported as having tone ‘a little reduced’, whereas all three of our cases had marked hypotonia in infancy and the two who did not show hypotonia on later testing were unable to sit unaided and were flaccid in their posture.
These three present cases provide further support for the absence of genetic factors in the aetiology.
Biochemical and cytological investiga- tions have all proved negative. There seem to be no features of possible aetiological significance in pregnancy or delivery. Although our Case 3 had, though by dates, the shortest gestation of all nine cases, he
was well within the normal weight range; Angelman’s Case 1 is the only one below 2.5kg at birth.
The diagnosis of the ‘happy puppet’ syndrome rests on the physical similarities of the cases reported to date and on the EEG pattern. Almost all the EEGS have shown recognisable spike wave complexes (Table Ill) which tend to be slightly slower in frequency than ‘classical petit mal’, and discharges are very frequent (‘almost continuous’, ‘more than half the recording time’). In spite of this, the spike wave activity is organised into fairly well- defined discharges and can be distinguished easily from the continuous, irregular slow waves with intermixed random spikes of hypsarrhythmia. The other characteristic feature of these cases is symmetrical theta rhythms, mostly between 4 and 6Hz. This finding is not, of course, unusual in children, particularly when they are upset or fractious, but its incidence seems to be unusually high in these cases and the rhythms seem to be less responsive to environmental circumstances or changes in apparent conscious level.
Acknowledgements: We thank the physicians who originally saw these children for referring them to this Department, Professor A. E. H. Emery for helpful discussions, and Dr. P. M. Jeavons for encouragement in preparing this report.
SUMMARY Three children with mental and physical retardation and with other features compatible
with Angelman’s ‘happy puppet’ syndrome are presented. Significant features of these children and the six previously published cases are tabulated. It now seems likely that this syndrome is a definite clinical entity, although the aetiology is still unknown.
R J ~ U M I ~ Trois nouveaux cas de ‘Marionnettes heureuses’
Trois enfants avec retard mental et physique et avec d’autres manifestations corres- pondants au syndrome de ‘Marionnette heureuse’ de Angelman sont dtudits. Les carac- ttristiques significatives de ces enfants et des six cas ddja publids sont analysds. I1 semble maintenant trks vraisemblable que ce syndrome soit une entit6 clinique dtfinie quoique 1’Ctiologie en soit encore inconnue.
68
CASE REPORTS
ZUSAMMENFASSUNG
Weitere drei ‘Happy Puppets’ Es werden drei Kinder beschrieben, die aul3er geistiger und motorischer Retardierung
noch andere Merkmale aufwiesen, wie sie bei Angelman’s ‘Happy Puppet’ Syndrom beschrieben sind. Die wichtigsten Symptome dieser Kinder und der sechs friiher veroffent- lichten Falle sind in einer Tabelle zusammengestellt. Man konnte sagen, daB dieses Syndrom ein umrissenes klinisches Krankheitsbild darstellt, von dem die Atiologie jedoch noch unbekannt ist.
RESUMEN Tres yelices rnui7ecas’ tnas
Se describen tres nifios con reraso mental y fisico y otras caracteristicas compatibles con el sindrome de Angelman ‘felices muiiecas’. Se exponen las caracteristicas significativas de estos niiios y de 10s seis casos publicados anteriormente. Parece probable actualmente que el sindrome sea una entidad clinica definida, aunque la etiologia es a6n desconocida.
REFERENCES Angelman, H. (1965) ‘ “Puppet” children. A report of three cases.’ Developnoend Medicine and Child
Berg, J. M., Pakula, Z . (1972) ‘Angelman’s (“happy puppet”) syndrome.’ American Journal of Diseases of
Bower, R. D., Jeavons, P. M. (1967) ‘The “happy puppet” syndrome.’ Archives of Disease in Childhood,
Neurology, 7,68 1.
Children, 123, 72.
42, 298.
The Cardiofacial Syndrome: Report of a Case with Severe Facial Palsy
J. K . Anand* L. J . Butlert
Introduction An association between congenital heart
disease and unilateral partial lower facial palsy was first recognised by Cayler (1967). He termed this ‘the cardiofacial syndrome’, and by 1971 he had observed a total of 30 cases (Cayler et a/. 1971). In contrast, he could find only six additional cases reported by other investigators since 1967.
In this report we present the findings in a 14-year-old boy discovered by one of us (J.K.A.) during routine medical examina- tions of pupils of a special school for the handicapped.
* Deputy M.O.H., HealthDepartment, London Borough of Redbridge, 17/23 Clements Road, Ilford, Essex.
t Senior Cytogeneticist, Queen Elizabeth Hosp- ital for Children, London E2 8PS.
CASE REPORT
This boy was born in 1957, the result of the third pregnancy of a mother aged 24. His father was aged 28. The two previous pregnancies had resulted in the births of normal females in 1953 and 1954. A threatened abortion had occurred at three months but no treatment had been given except for bed-rest. Delivery was normal by the vertex at 40 weeks; the birthweight was 2,495g. There was no history of illness during the preg- nancy, no drugs were taken, and the mother had received no form of irradiation.
On examination at the age of 14 years, the boy was found to be of low-normal intelligence, with normal hearing. His vision was 6/30 in the right eye and 6/9 in the left (Snellen) without spectacles. The right ear was larger than the left and there was obvious facial nerve palsy of the lower motor neurone type on the left side. The thorax appeared to be normal clinically, but there was radiological evidence of hemivertebrae and spina bifida in the
69