cerebro-facio-thoracic dysplasia: report of three cases

9
CASE REPORTS ZUSAMMENFASSUNG Faciale Myokymie in Verbindung rriit Medulloblastom Es wird iiber einen 5 Jahre alten Jungen berichtet, der einen communizierenden Hydro- cephalus hatte und bei dem eine einseitge faciale Myokymie schlieBlich zur Diapose fuhrte. Die mogliche Pathophysiologie der Myokymie und ihre Bedeutung als klinisches Symptom werden diskutiert. RESUMEN Mioquimia facinl asociada a riiedulobiastoma Se aporta un caso de meduloblastoma en un niiio de 5 aiios de edad que presentaba una hidrocefalia comunicante. en la que la presencia de una mioquimia facial unilateral condujo finalmente a1 diagnostico. Se discute la posible patofisiologia de la niioquimia y su importancia como signo clinico. REFERENCES De Silva, K. L., Pearce, J. (1972) 'Facial myokyniia: a clue to the diagnosis of multiple sclerosis.' Postgraduate Gutniann, L., Thompson, H. G.. Martin, J. D. (1969) 'Transient facial myokymia. An uncommon mani- Kaeser, H. E., Richter, H. R., Wuthrich, R. (1963) 'Les dyskinesies faciales.' Revue Nwrolugiqur, 108, 538. O'Connor, P. J., Parry, C. B., Davies, R. (1966) 'Continuous muscle spasm in intramedullary tumours of Tenser, R. B., Corbett, J. J. (1974) 'Myokymia and facial contraction in brain stem glioma. An electro- Medical Journal, 48, 657. festation of multiple sclerosis.' Journal qf rltc. Aincrican Medical Association. 209, 389. the neuraxis.' Journal of Neurology, Neurosurgery arid Psychiafrj,, 29, 3 10. myographic study.' Archives of Nerrrolo~~., 30. 425. Cerebro-Facio-Thoracic Dysplasia: Report of Three Cases I. Pascual-Castroviejo J. M. Santolaya V. Lovez Martin T. Rodriguez- Costa Introduction There are many syndromes in which mental retardation is associated with a characteristic facial appearance, and others in which major or minor abnornial- ities of the spine occur together with facial deformities, which are often uni- lateral. Cases have been reported in whom mental retardation, characteristic facies and vertebral abnormalities have been found, as in 'Coffin's syndrome' (Coffin et al. 1966). In this paper three patients are reported in whom there was significant mental retardation, a typical facial appearance and abnormalities of the vertebrae and ribs. A. Tender0 F. Mulas Case Reports CASE 1 This girl, the eldest of three children, was referred to us at the age of 7j years on account of retarded motor and mental development. In the family history both her father and mother (aged 27 and 23 years respectively at the time of the daughter's birth) were healthy, as were her two brothers. The parents were second cousins. Two of her mother's first cousins suffered from mental retardation of unknown origin. The child had been delivered by the vertex at an estimated 42 weeks gestation. Birthweight was 3200g. She was cyanosed at birth but crying was initiated after back-slapping. The only abnormality noted on examination was a short neck. Her behaviour during the neonatal period was normal. At the age of I0 months she had been referred Clinica Infantil 'La Paz', Madrid 20, Spain. 343

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CASE REPORTS

ZUSAMMENFASSUNG Faciale Myokymie in Verbindung rriit Medulloblastom

Es wird iiber einen 5 Jahre alten Jungen berichtet, der einen communizierenden Hydro- cephalus hatte und bei dem eine einseitge faciale Myokymie schlieBlich zur Diapose fuhrte. Die mogliche Pathophysiologie der Myokymie und ihre Bedeutung als klinisches Symptom werden diskutiert.

RESUMEN

Mioquimia facinl asociada a riiedulobiastoma Se aporta un caso de meduloblastoma en un niiio de 5 aiios de edad que presentaba una

hidrocefalia comunicante. en la que la presencia de una mioquimia facial unilateral condujo finalmente a1 diagnostico. Se discute la posible patofisiologia de la niioquimia y su importancia como signo clinico.

REFERENCES De Silva, K. L., Pearce, J. (1972) 'Facial myokyniia: a clue to the diagnosis of multiple sclerosis.' Postgraduate

Gutniann, L., Thompson, H. G.. Martin, J. D. (1969) 'Transient facial myokymia. An uncommon mani-

Kaeser, H. E., Richter, H. R., Wuthrich, R. (1963) 'Les dyskinesies faciales.' Revue Nwrolugiqur, 108, 538. O'Connor, P. J., Parry, C. B., Davies, R. (1966) 'Continuous muscle spasm in intramedullary tumours of

Tenser, R. B., Corbett, J. J. (1974) 'Myokymia and facial contraction in brain stem glioma. An electro-

Medical Journal, 48, 657.

festation of multiple sclerosis.' Journal qf rltc. Aincrican Medical Association. 209, 389.

the neuraxis.' Journal o f Neurology, Neurosurgery arid Psychiafrj,, 29, 3 10.

myographic study.' Archives of Nerrrolo~~., 30. 425.

Cerebro-Facio-Thoracic Dysplasia: Report of Three Cases

I . Pascual-Castroviejo J . M . Santolaya V. Lovez Martin T . Rodriguez- Costa

Introduction There are many syndromes in which

mental retardation is associated with a characterist ic facial appearance, and others in which major or minor abnornial- ities of the spine occur together with facial deformities, which are often uni- lateral. Cases have been reported in whom mental retardation, characteristic facies and vertebral abnormalities have been found, as in 'Coffin's syndrome' (Coffin et al. 1966).

In this paper three patients are reported in whom there was significant mental retardation, a typical facial appearance and abnormalities of the vertebrae and ribs.

A . Tender0 F. Mulas

Case Reports CASE 1

This girl, the eldest of three children, was referred to us at the age of 7j years on account of retarded motor and mental development. I n the family history both her father and mother (aged 27 and 23 years respectively at the time of the daughter's birth) were healthy, as were her two brothers. The parents were second cousins. Two of her mother's first cousins suffered from mental retardation of unknown origin.

The child had been delivered by the vertex at an estimated 42 weeks gestation. Birthweight was 3200g. She was cyanosed at birth but crying was initiated after back-slapping. The only abnormality noted on examination was a short neck. Her behaviour during the neonatal period was normal.

At the age of I0 months she had been referred

Clinica Infantil 'La Paz', Madrid 20, Spain.

343

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1975, 17

t o a paediatrician because she could not hold up her head in the erect position, She did not smile, seemed indifferent to her environment and made no effort to reach for objects. Her weight was 9100g (60th centile) and her height was 75cm (60th centile). The occipito-frontal circumference was 44cm (- 0.75 S.D.), the skull being brachy- cephalic with a flat occiput and a narrow forehead. The nasal bridge was wide, the ears low-set and the neck was short, with excessive skin over the nape. The scapulae were elevated and prominent and there was a dorso-lumbar kyphosis. There was convergent strabismus, predominant in the left eye. No definitive diagnosis was reached and she was sent to another paediatric centre where thyroid hormone was given, without apparent improvement.

She did not walk until the age of two years and when she was seen at the age of 2 years 1 1 months she walked with her feet very wide apart. At this time she weighed 15’8kg (75th percentile) and her height was 98cm (75th per- centile). She could say three or four words. It was noted that the inferior part of her chest was sunken.

A Gesell Test was administered and in spite of her lack of attention her development quotient was found to be: motor behaviour 21 months; adap- tive behaviour 13 months; language 18 months; personal-social I8 months.

At the age of 7% years she could feed herself but could not dress herself and was incontinent of urine and faeces. She was placid but showed little interest in toys or in playing with other children. Her speech was still limited to a few words.

On examination at age 7%. the following find- ings were noted. Occipito-frontal circumference 51.5cm (75th percentile), low hair-line, narrow forehead, anti-mongolian slant of the palpebral fissures, bushy eyebrows growing together, broad nasal bridge with a short nose, and a triangular mouth with a wide philtrum. The neck was short and showed bilateral skin folds. The nipples were low-set and the hair-line posteriorly was low (Figs. 1 and 2). Muscle tone was normal and tendon jerks were within normal limits. In walking, she dragged her widely-separated feet. There was bilateral convergent strabismus but the fundi were normal and there were no opacities in the cornea or lens. The results of the tests of thyroid function were normal.

Radiological studies showed that the cranium was brachycephalic and the occipital bone was flat. The sella turcica was small and the posterior clinoid processes were large. The inter-orbital distance was disproportionately large and there was overdevelopment of the frontal sinuses. Calcification of the falx cerebri was noted. There was hypoplasia of the superior maxilla, the mand- ible being prominent. X-rays of the chest showed multiple exostoses forming bridges between the posterior parts of the first five ribs on both sides. Some of these bridges extended a considerable distance towards the anterior parts, giving an appearance that the ribs were bifid. Other ribs were truly bifid, this being most obvious in the first rib on the right side. In the spine there was a moderate scoliosis, concave to the right, maximal in the D4-5 region. The cervical column showed multiple abnormalities, there being bony union down to the level of the 6th dorsal vertebrae. There were also hemi-vertebrae and wedged verte- brae in the cervical and superior part of the thoracic regions. The hips appeared to be normal. Bone age was normal.

The electroencephalogram showed no abnorm- ality. No abnormalities of the chromosomes were found. Derrnatoglyphic analysis showed distal displacement of the axial triradius and hypothenar whorls.

Fig. 1 (kfl). Case I . General aspect, showing facial alterations, short neck and widely-separated This girl was admitted to o u r clinic at the acre

CASE 2 I -

of five years on account of motor and intellectual retardation. In the family history, the child’s mother. 28 years old at the time of her daughter’s

mammillae. Fig. 2 (right). Case 1. View of back and occipital region of head, showing thick neck, low hairline and elevated scapulae.

344

CASE REPORTS

birth, was healthy. Her father, 32 years old, had synophrys (joining of the eyebrows in midline). She had two healthy brothers age 8 and I I years. The mother's first cousin was mentally retarded but was married and had two normal children. She was delivered by the vertex I S days after the expected date after an uncomplicated pregnancy. The labour was prolonged and she was apnoeic after birth, requiring slapping before crying started. Birthweight was 4160g. No abnormalities were noted at the time of birth and the neonatal course was uncomplicated. At the age of four months she suffered from bronchitis.

She did not hold up her head in the erect position until the age of IS months and walked without support only at 22 months.

When studied at the age of five years she could speak using only bisyllables and had no sentences. She was not reliably toilet-trained but could feed herself and tried to dress herself. She was of placid disposition and had good relationships with her brothers. She had had an operation for an in- guinal hernia.

Examination showed a child 119cni in height (90th percentile) with a n occipito-frontal c i rc tm- ference of 54cm and a weight of 20kg (75th per- centile). The skull was brachycephalic, the hair was abundant and coarse and the hair-line was low anteriorly and posteriorly (Figs. 3 and 4). As in Case I . the face was broad and the forehead narrow, with frontal bossing. The bushy eyebrous spanned the bridge of the nose. There was hyper- telorism. with epicanthic folds, and the nose u a \

short and the nostrils anteverted. The mouth was triangular and the teeth were small, yellow and separated one from another. The ears had normal lobes but were low-set. The general impression was of a flat bcial profile. largely owing t o the lack of angle between the forshezid and the nose. The short neck showed limited lateral movement. The scapulae stood out a t the shoulders and were close together. The lower third of the sternum appeared to be indrawn. There was abundant hair o n the upper limbs and on thc back. N o defects were noted o n examination o f the alimentary. cardiovascular o r respiratory systems and the skull appeared to be normal. No defects of the eyes were noted. The child was generally slightly hypotonic, with normal tendon jerks, but volun- tary movements were slow and clumsy. She gave the impression of being nienrally retarded, though she was capable of co-operating in the examination.

Haematological findings were normal, the urine was normal on routine testing, and aminoacid chromatography findings were normal. N o ab- normalities were found in the cerebrospinal fluid and the blood calcium phosphorus and alkaline phosphatase were normal. Cholesterol was I300,'l and blood lipids 4.39g 1. The bone-marrow was within normal limits.

X-rays of the skull showed hypoplasia of the superior maxillary bones, uith a prominent mand- ible. The mandibular bones appeared to be rather square. The sella turcica was small and the inter- clinoid ligaments were calcified. There was broad- ening of the bones and hypercalcification of the

Fig. 3 (lefr). Case 2. Peculiar facies with bushy eyebrows, synophrys, short nose, wide philtrum, inverted-\/ mouth and narrow forehead. Fig. 4 (right). Case 2. Dorsal view of neck and trunk, jhowing low hairline. Scapulae are elevated and close together.

345

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1975, 17

skull bones in the posterior fossa. There was lack of development of the frontal sinuses (Fig. 5). X-rays of the chest showed the upper thorax to be narrow and there was some exostosis of the inferior surface of the posterior part of the right second rib. The posterior part of the right third rib was fork-shaped and reached the axilla; at the level of this fork there was an osseous bridge between the third and fourth right ribs. The direction of the posterior parts of the fourth, fifth and sixth ribs on the right was irregular. The third left rib appeared to be enlarged and the alignment of the anterior portion deviated from that of the related ribs. There was fusion of the posterior parts of the fourth, fifth, sixth and seventh ribs. The lower ribs were flared. 13 ribs were present on each side. In the spinal column, rudimentary thoracic ribs were found on the first dorsal vertebra, the one on the left being fused with the seventh cervical vertebra. The sixth and seventh cervical vertebrae appeared to be fused on the left and there was a block formation of the second, third, fourth, fifth and sixth thoracic vertebrae (Fig. 6).

Pneumoencephalography at eight months of age demonstrated a ‘cavum velum interpositum’; when repeated at five years of age, enlargement of the septum pellucidum was demonstrated.

Electroencephalography revealed an abnormal tracing in which there were bilateral bursts of spikes and slow waves. Analysis of the chromo- somes revealed no abnormality. The dermato- glyphic analysis showed thenar vestiges only.

On the Gesell Test, performed at 5 years 2 months, the developmental quotient was as follows: motor behaviour 42 months; adaptive behavior 30 months; language 18 months; per-

sonal-social 30 months. The intelligence quotient was 48.

CASE 3 This boy was the illegitimate son of the mother

and her second cousin. The mother had five earlier legitimate children (including one pair of twins). The child was brought to our centre at three years of age on account of motor retardation and microcephaly. He had been delivered by the vertex after an uncomplicated pregnancy, a t an estimated gestation of 40 weeks. He cried at birth and weighed 4kg. No abnormal- ities were noted at birth except that the head was rather large. The behaviour during the neonatal period was unremarkable and during the first months of life he appeared to be healthy. At the age of five months, however, he suffered from bronchitis and from that time onwards the parents noted a convergent squint. At five months he could not hold up his head. At 16 months he began to walk slowly, with frequent falls which seemed to occur more often as he grew older. He did not appear to be mentally retarded in com- parison with children of the same age.

At the age of 3 years 3 months he could feed himself but could not dress himself without help. He had just become continent of urine. He played with toys and seemed friendly, but his movements were sluggish. His speech seemed to be normal. There was no history of convulsions. He was unlike other members of his family.

On examination, his height was lO2cm (97th percentile) and his crown-rump length was 60cm (90th percentile). His occipito-frontal circumfer- ence was 54cm (97th percentile). His head appeared to be large and the face hypoplastic (Fig. 7). His

Fig. 5 (lefr). Case 2. Calcification of interclinoid ligaments, small anterior fossa, hypoplasia of maxilla, prominent mandibula with wide angle. Fig. 6 (right). Case 2. Alterations in ribs and vertebrae in superior half of thorax and inferior part of cervical column.

346

CASE REPORTS

Fig. 7 ( I f + ) . Case 3 . General aspect of patient. bhowing peculiar facies and strabismus. Fig. 8 (righr). Case 3 . Profile, showing hypopla\ia of maxillary region and prominence of lower lip.

hair was bushy and there was a low hair-line, especially anteriorly and laterally. Some hair was present between the eyebrows. The forehead was narrow and his short nose showed no angle with the forehead and appeared on a lateral view to be in a straight line with it. The mouth uas triangular, with a broad philtruni and thick lips. The superior maxillae were hypoplastic and the cars were low-set (Fig. 8). The large t r u n k appeared to be disproportionate with the limbs. The thorax was narrow and there was little niuscle bulk covering it. His scapulae were elevated. The genitals were normal, except for a testicular hydrocele on the right.

Neurological examination showed a convergent bilateral strabismus and generalised mild hypo- tonia. The tendon jerks were all increased, though the plantar responses were flexor. He walked slowly and tended to drag the right leg. He appeared to prefer to use his left hand.

Investigation resulted in normal haematological tindings (blood calciuni 102nig I. phosphorus 38mg'I, alkaline phosphotase 171 UKA,'I) . All other investigations of the blood, including blood sugar and arninoacid chromatography, were sugar and aminoacid chromatography. were normal. Cerebrospinal fluid showed no abnormal- ity. The urine aminoacid chrornatogram was normal.

X-ray of the skull showed brachycephaly, with marked hypoplasia of the superior niaxillary bones and poorly-developed frontal and maxillary sinuses. There was calcification of the interclinoid ligaments (Fig. 9). The fourth rib on the right showed forking posteriorly: the upper branch of the fork extended for only a centimetre, while the lower branch distorted the thoracic cage. The fourth rib on the left showed a similar but less marked abnormality. The lower ribs were flared bilaterally. The tirst and second dorsal vertebrae were fused and the fourth and fifth dorsal verte- brae showed wedging. The third cervical vertebrae was abnormal. There was spina bifida occulta at SI. The urists and bones of t h e limbs appeared to be osteoporotic but the bone age was normal.

Pneumoencephalography showed hypoplasia of the corpus callosiim (Fig. 10). The electroence- phalogram showed generalised slowing. especially on the left. Chromosome studies were normal. Derrnatoglyphic analysis showed distal displace-

Fig. 9 (k/i) . Case 3 . Calcification of intercliniod ligaments. Anterior fossa is small, with hypoplastic maxilla and prominent mandible. Fig. 10 (righr). Case 3. Pneumoencephalograni showing hypogenesis of corpus callosum.

347

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1975, 17

ment of the axial triradius and hypothenar buckle. At the age of 3 years 4 months the developmental

quotient on the Gesell Test was: motor behaviour 24 months; language 24 months; personal-social 30 months.

Discussion The three patients have a number of

characteristic clinical features in common (Table I).

It appears that the syndrome may affect both sexes. That two of the patients had a family history of mental retardation is of doubtful importance. Unfortunately we were unable to examine the relatives, though we were assured that their facial appearance was different from that of the patients’. Thus it would seem there are two possibilities: (a) that the process is not hereditary; or (b) that it is hereditary and may be due to an autosomal recessive trait.

The second possibility seems more likely in view of the finding that the parents were second cousins in two of the three cases. The fact that both males and females were affected excludes the possibility of a sex-linked inheritance, though the two female patients were more affected than the male patient. No characteristic derma- toglyphic pattern was found.

The differential diagnosis is between the Cornelia de Lange syndrome (Castroviejo 1971), spondylo-thoracic dysplasia (Van der Sar 1952, Lavy et a/. 1966, Rimoin et a/. 1968, Castroviejo et a/. 1973), the Coffin syndrome (Coffin et a/. 1966, Maroteaux 1968, Procopis and Turner 1972), the Rubinstein-Taybi syndrome (Rubinstein and Taybi 1963, Castillo et a/. 1972), the Smith-Lemli-Opitz syndrome (Smith et a/. 1964), the Weill-Marchesani syndrome (Castroviejo 1971), and some conditions in which congenital heart disease is found in association with marked bony defects in the thorax.

The facial appearance in the de Lange syndrome is very similar to that found in

cerebro-facio-thoracic dysplasia, for there is synophrys (joining of the eyebrows in midline), a narrow forehead and a short nose; there are also hypertrichosis (espec- ially posteriorly) and mental retardation. However, patients suffering from the de Lange syndrome do not show radiological abnormalities in the thorax, and there is no hypoplasia of the maxillae, the mouth is not triangular and the head tends to be smaller. Limb abnormalities occur fre- quently in the de Lange syndrome but these are not a feature of cerebro-facio- thoracic dysplasia.

In spondylo-thoracic dysplasia the ab- normalities of the vertebrae and ribs tend to be more severe than those in cerebro- facio- thoracic dysplasia and extend throughout the thorax. These result in the trunk being short and the extremities dis- proportionately large, whereas in cerebro- facio-thoracic dysplasia the only abnor- malities are confined to the upper half of the body and there is no disproportion in the length of the trunk and extremities. The facies is normal in spondylothoracic dysplasia and mental retardation is not a feature. The modes of inheritance are either autosomal dominant (Van der Sar 1952, Caffey 1967, Peralta et al. 1967, Rimoin et a/. 1968) or autosomal recessive (Jarcho and Levin 1938, Levy et al. 1966, Moseley and Bonforte 1969, Pochaczevsky et a/. 1971, Castroviejo et a/. 1973). Abnormalities are usually more severe in patients in whom the inheritance appears to be autosomal recessive.

The Coffin syndrome (Coffin et a/. 1966) also has some similarities with the cerebro- facio-thoracic dysplasia syndrome. There is a characteristic facies with a prominent forehead, markedly arched eyebrows, hypertelorism, an anti-mongolian slant of the palpebral fissures and relative hypo- plasia of the maxillae and mandible. There is also prognathism, wide separation of the teeth, and a broad nasal septum. How-

348

CASE REPORTS

TABLE I Clinical, morphological and radiographic features in three cases

Features

Clinical Sex

Pregnancy Birth Motor development Intelligence Character Neurological

Other

Age

abnormalities

~ ~ ~ ~~~

Morphological Skull Hairline Forehead Eyebrows Eyes

Nose Filtrum Mouth Ears Profile Neck

Scapulae

Trunk

Radiographic Skull

Face

Thorax: ribs

vertebrae

Pneumoencephalography

Case I

Female 7f years Normal Anoxic Retarded

Affable Conv. strabismus, clumsy walk

IQ 49

Brachycephaly Low Narrow Synophrys Epicanthus, hypertelorism Broad, short Wide Inverted V Low-set Flat Short, bila t . skin folds Elevated, close together Thorax narrow, sunken inferior part

Calcification inter- clinoid ligament Maxillarv hvoodasia.

Case 2

Female 5 years Normal Anoxic Retarded

Affable Clunisy walk, lack of agility Bilat. inguinal hernia

IQ 48

Brachycephaly Low Narrow Synophrys Epicanthus, hypertelorism Broad, short Wide Inverted V Low-set Flat Short

Elevated, close together Thorax sunken inferior part

Calcification inter- clinoid ligament Maxillary hypoplasia.

promineht m:dnhibula'r prominent mandibular

Case 3

Male 3 years Normal Anoxic Retarded IQ 64 Affable Conv. strabismus, clumsy walk Perito-vaginal channel open

Macrocephaly Low Narrow Synophrys Epicanthus, hypertelorism Broad, bhort Wide Inverted V Low-set Flat Short

Elevated, close toget her Thorax narrow

Calcification inter- clinoid ligament Maxillary hypoplasia

region region Bilat. exostosis causing bifid ribs, bridged ribs Fusions. wedged and Fusions. spina Fusion.; hemi-vertebrae bifida - Large septum Hypogenesis of

pellucidum corpus callosum

As Case I ( I3 ribs) A5 Case 1

ever, the striking clinical and radiological cerebro-facio-thoracic syndrome, those signs in the Coffin syndrome include broad with the Coffin syndrome have more soft hands, a keel-shaped chest, relaxed marked facial abnormalities. less marked ligaments and bony abnormalities affecting abnormalities of the eyebrows, and the particularly the thoracic and lumbar ver- hair of the scalp is not so low-set. No tebrae, which may cause a kyphosis because abnormalities of the ribs have been of collapse of the vertebral bodies. Mental described in the published cases. The retardation is severe. Histologically there syndrome appears to be due to an auto- is a lack of elastic fibres in the skin and a soma1 recessive trait (Maroteaux 1968, disordered pattern of cartilaginous and Martinelli and Campailla 1969, Gonzalez osseous structures in the epiphyseal zones. Elipe et a/ . 1971, Procopis and Turner Compared with patients suffering from the 1972).

349

DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY. 1975. 17

AUTHORS’ APPOINTMENTS paediatric Service, Clinica Infantil ‘La Paz’. Dr. 1. Pascual-Castroviejo, Head, National Neuro- Dr. T. Rodriguez Heady Section*

Generalisimo 177, Madrid, Spain. Dr. A. Tendero, Assistant Physician, Neuro- Dr. J. M. Santolaya, Head of Neuropaediatric paediatric Service, Clinics Infanti1 ‘La Paz’. Section, Hospital Civil de Basurto, Bilbao. Dr. F. Mulas, Assistant Physician, Neuropaediatric Dr. V. Lopez Martin, Head, EEG Section, Neuro- Service, Clinica Infantil ‘La Paz’.

paediatric Service, Clinics Infanti1 *La paz’, Avda, Neuropaediatric Service, CIinica Infanti1 ‘La Paz”

SUMMARY Three children, two girls and one boy, are described as suffering from a new syndrome,

‘cerebro-facio-thoracic dysplasia’. The characteristic findings are mental retardation, characteristic facies, narrow forehead, bushy eyebrows with synophrys, hypertelorism, broad nose, wide philtrum, triangular-shaped mouth, short neck, marked maxillary hypoplasia, a low hairline (especially posteriorly in the midline on the neck), brachy- cephaly, calcified clinoid ligaments, and multiple bony abnormalities in the upper thoracic vertebrae and sometimes in the cervical region, together with a variety of deformities of the upper ribs. It seems possible that the condition is hereditary and that it may be inherited as a result of an autosomal recessive trait.

ZUSAMMENFASSUNG Cerebro-facio-thorakale Dysplasie: Bericht uber drei Falle

Drei Kinder, zwei Madchen und ein Junge, mit einem neuen Syndrom, genannt ‘Cerebro- facio-thorakale Dysplasie’, werden beschrieben. Die charakteristischen Befunde sind geistige Retardierung, charakteristische Facies, enge Stirn, buschige Augenbrauen uber der Nasenwurzel zusammengewachsen, Hypertelorismus, breite Nase, breites Lippenphiltrum, dreieckiger Mund, kurzer Hals, ausgepragte Kieferhypoplasie, tiefe Haaransatzlinie (besonders in der Mitte des Nackens), Brachycephalie, verkalkte klinoide Ligamente und multiple Knockenveranderungen der oberen thorakalen Wirbel und manchmal auch im Halsbereich, zusammen mit vielfaltigen Deformierungen der oberen Rippen. Es erscheint moglich, da13 das Krankheitsbild erblich ist und wahrscheinlich autosomal recessiv vererbt wird.

RESUMEN Displasia cerebro-facio-torcicica: Aportacibn de fres casos

Tres niiios, dos hembras y un varon son descritos como portadores de un nuevo sindrome llamado ‘Displasia cerebro-facio-toracica’. Los hallazgos caracteristicos son : retraso mental, facies especial, frente estrecha, cejas pobladas con sinofria, hipertelorismo, nariz ancha, philtrum amplio, boca de forma triangular, nariz corta, marcada hipoplasia maxilar, implantacidn baja del cabello (sobre todo en la parte posterior de la linea media del cuello), braquicefalia, ligamentos clinoideos calcificados y multiples anomalias 6seas de las ver- tebras toracicas altas y a veces de la region cervical, juntamente con una variedad de deformaciones de las costillas superiores. Parece posible que la alteracion sea hereditaria y que puede ser heredada como consecuencia de una tendencia recesiva autosomica.

REFERENCES Caffey, J . (1967) Pediatric X-Ray Diagiiosis, 5th Edn. Chicago: Yearbook Medical Publishers. Castroviejo, I. P. (1969) ‘Malformaciones del cuerpo calloso y del tabique transparente. Clasificacion por

- (1971) Diagnostic0 Clinico-radiologico en Neurologie Infantil. Barcelona : Edit. Cientifico-Medica, estudio neumoencefalografico.’ Radiologia, 67, 3.

pp. 60,242, 244. -Rodriguez-Costa, T., Castillo, F. (1973) ‘Spondylo-thoracic dysplasia in three sisters.’ Developmental Medicine and Child Neurology, 15, 348.

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CASE REPORTS

Coffin, G. S., Siris, E., Wegienka, L. C. (1966) ‘Mental retardation with osteo-cartilagenous anomalies.‘ American Journal of Diseases of Children, 112, 205.

del Castillo, F., Lopez Martin, V., Rodriguez-Costa, T., Castroviejo, I. P. (1972) ‘Sindrome de Rubinstein- Taybi (estudio sobre ocho casos).’ Archiros de Neurobiologia. 35.425.

Gonzalez Elipe, J., Fernandez Criado, M., Bermeja Pareja, F., Garcia de Yebenes, J., Diez Torres, 1. (1971) ‘Sindrome de Coffin.’ Paper presented at the 23rd Annual Meeting of La Sociedad Espaiiola Neurologia, Barcelona.

Jarcho, J., Levin, P. M. (1938) ‘Hereditary malformation of the vertebral bodies.’ Bulletin of the Johns Hopkins Hospital, 62, 216.

Lavy, N. W., Palmer, G. C., Merrit, A. D. (1966) ’A syndrome of bizarre vertebral anomalies.’ Journal of Pediatrics, 69, 1121.

Maroteaux, P. (1968) ‘Une observation de syndrome de Coffin.’ Archives Francaises de Pkdiatrie, 25, 116. Martinelli, B., Campailla, E. (1969) ‘Contributo alle conoscenza della sindrome di Coffin.’ Giornale di

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