Contribution of magnetic resonance imaging to the knowledge of CNS malformations related to chromosomal aberrations

J. C.Tamraz1,2, Marie-Odile Rethoré2, Marie-Thérèse Iba-Zizen1, J. Lejeune2, and E. A.Cabanis1

Hum Genet (1987) 76:265-273


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Introduction

Few anatomical and pathological data are available concerning the central nervous system malformations observed in association with human chromosomal diseases. Most data have been collected from post-mortem studies and frequently with poor clinicopathological correlations. A better understanding of the malformation phenotypes needs more extensive clinical, cytogenetical, and anatomical evaluations. Using magnetic resonance imaging, with its in vivo three-dimensional approach of skull and brain anatomy, more gross neuropathological data should be added to the already known malformations related to chromosomal aberrations and other congenital syndromes.

Moreover, it is also well established that radiologic features sometimes contribute to the identification and differentiation of many of these chromosomal diseases, as do cranio-facial dysmorphy, dermatoglyphics, and certain ocular and/or auricular findings, particularly when associated with mental retardation or family history. The aim of this work is to present the magnetic resonance morphological findings observed in some of the chromosomal syndromes and correlate them to pathologic anatomical findings.

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Materials and methods

Twelve patients were studied using magnetic resonance imaging (MR) for 13 months (from January 1985 to February 1986). These patients were collected from more than 2200 nervous system MR examinations performed in the Department of Neuroradiology at the Centre National d'Ophtalmologie des Quinze-Vingts in Paris. There were seven patients with trisomy 21 syndromes, two with duplication syndromes, and three patients with deletion syndromes. Three of the patients were under 3 months of age. The other nine were aged from 12 years to 35 years (mean age 25.5 years). MR examination could not be performed in a patient with trisomy 21 syndrome because of fear and claustrophobia. All the patients had clinical evaluations with long-term follow-up history including an evaluation of their psychomotor development. Dermatoglyphics and cytogenetic studies were performed at the Institut de Progénèse in Paris. In all cases the chromosomal aberrations have been demonstrated on karyotypes. The main clinical data on our patients, particularly those concerning craniofacial dysmorphy, associated neurological signs and symptoms, and mental status are reported. Tables 1 and 2 summarize the data on age, sex, height, weight, head circumference, and intelligence quotient (IQ) as evaluated according to the Binet-Simon scale. Patients with trisomy 21 syndrome (1-7), being a very homogeneous group, are separated from the other patients with various duplication or deletion syndromes.

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Case reports

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Patients (1-7) with trisomy 21 syndromes (Table 1)

All seven patients ranging in age from 12 to 35 years, showed the characteristic craniofacial dysmorphy including the round facies with its flat profile, the upslanting palpebral fissures, and the small ears (Lejeune et al. 1959). However, some clinical findings need to be added in each case.

Patient 1. Congenital nystagmus; agenesis of median inferior incisors; genu valgum; recurrent torticollis.

Patient 2. Cataract; unsteadiness of gait: relapsing episodes of faintness and/or syncope since 1976; seizures from 1979: normal interietal encephalogram.

Table 1. Patients with trisomv 21 svndrome. H.C., Head circumference; IQ, intelligence Quotient; (...). MR file number
Case no.PatientsAge (years)KaryotypesHeight (m)Weight (kg)H.C. (cm)IQ
1BOU. N. (995)1847,XX,+211.34364942
2LAR.S. (424)3547,XX,+211.46545334
3GAU.V. (775)2547,XX,+211.46485039
4DUF.A. (305)2047,XX,+211.52455257
5SEV.R. (996)3547,XX,+211.42525021
6BOU.E. (987)1247,XY,+211.27265227
7PAS.F. (1121)3247,XY,+211.61665340
Table 2. Patients with duplication (8-9) or deletion (10-12) syndromes
Case no.PatientsAgeKaryotypeHeight (m)Weight (kg)H.C. (cm)IQ
8LEV. C. (905)6 days47,XX,+130.482.6532-
9PER. A. (463)2.5 months47,XX,+180.462.3535.5-
10NOC.M. (107)2 months46,XX,del(4p)0.472.1532-
11HAC.H. (1925)26 years46,XX,del(5p)1.505652.555
12TIS.M. (917)27 years46,XX,del(7)(p12)1.57345130

Patient 3. Arterial hypotension; vertigo; recurrent torticollis and upper thoraco-spinal pain; hyperflexibility of superior cervical spine; small auricular septal defect.

Patient 4. Mild tremor of the extremities; no known malformations; very good social and professional adaptation.

Patient 5. Tremors of the extremities; catatonia; Alzheimer disease; acne.

Patient 6. Lymphangioma of the tongue; agenesis of median superior incisives.

Patient 7. Baldness; dorsal kyphosis; polydipsia for 10 years; discordant behavior with episodes of autism and mania.

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Patients (8-9) with other duplication syndromes (Table 2)

Patient 8. Trisomy 13 syndrome; bilateral microphthalmus and enophthalmos; absence of cleft palate; hypoplastic uvula; hexadactyly; hypoplasia of left heart cavities and hypoplastic aorta; relatives with normal karyotype; death 11 days after birth. Autopsy study completed.

Patient 9. Trisomy 18 syndrome with the characteristic cranio-facial dysmorphy; co-twin 46,XX; relatives with normal karyotype; large anterior fontanel; moderate ventricular dilation on brain ultra-sound; short sternum; supplicating attitude; death a week after birth.

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Patients (10-12) with deletion syndromes (Table 2)

Patient 10. 4p- Syndrome wilh its characteristic craniofacial dysmorphy (Rethoré 1977) including hypertonicity of skin muscles of the forehead, broad nose and wide glabella, ocular hypertelorism and strabismus, receding jaw and narrow philtrum, ogival palate, and bilateral preauricular pits. Particular findings include the following: large anterior fontanel and metopic " suture "; microcephaly with cranium bifidum "a minima"; Marcus-Gunn jaw-winking phenomenon; absence of pupillomotor responses to light; still no seizures; cardiome-galy with large auricular septal defect on cardiac catheterization; major hypotrophy.

Patient 11. 5p- Syndrome with its well established phenotype (Lejeune et al. 1963,1964; Rethord 1977; Breg et al. 1970) including microcephaly, hypertelorism, and protrusion of the mediofrontal region. In this case head tremor, tremulation of the extremities, and a dorsal kyphosis are also found.

Patient 12. Partial monosomy 7p; cleft palate; myopia; arachnodactyly; dorsal kyphosis; hypotrophy; mania; marked mental retardation.

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Methods

Magnetic resonance imaging was performed on a prototype resistive magnet (Magniscan 1500) operating at 0.15 Tesla. Two radiofrequency pulse sequences were routinely used: the spino-echo (SE) and the inversion-recovery (IR) modes. The SE pulse sequence was performed in all cases using a short echo time (TE: 30-40 ms) and a short repetition time (TR: 350-500) in order to obtain highly morphological, T1-weight-ed images. A complementary T2-weighted pulse sequence with a long TE (60-120 ms) and a variably long TR (1250-1750 ms) was performed in most cases due to its high detection sensitivity of disease. The IR pulse sequence was used in a few cases because of long time consumption compared to shurt SE sequences. However, IR is the best sequence to use if cortical architecture, gray matter heteropia, and/or disorders of myelination need to be more accurately evaluated.

Whatever the pulse sequence used, data were displayed on a 256 x 256 matrix, using a two-dimensional Fourier transform technique. The number of excitations varied from 2 to 4 with long and short SE pulse sequences respectively. The slice thickness, always the same in each image plane, was 9 mm. The global examination time ranged from 45 to 90 min and sedation using intra-rectal thiopenthal (25 mg/kg) was used in infants and children under the age of 5 years.

Table 3. Morphological MR findings in patients with trisomy 21 syndrome: skull, face, and spine
MR features and findingsPatients no.
1234567
Brachycephaly++++-++
Shortening of anterior segment of the base+++++-+
Increase in angle of basi-cranium (sphenoidal angle)+++++--
Delayed maturation of sphenoid bone-+++++-
Rectitude of cervical spine+-+++/-+/-+
Malformation of cranio-cervical junction--+----
Spina bifida occulta--+----
Large cisterna magna-+++--+
Arachnoid cyst of posterior fossa---+---
Lymphangioma of the tongue-----+-

Family members usually accompanied the patients during the examination. This was particularly helpful in the mentally retarded patients and very timorous trisomy 21 patients. Much patience and kindness was needed to avoid having to recourse to sedative drugs. Absolute sedation is essential when the patient was unable to remain still voluntarily, because any motion degrades the image irreparably, due to the very long imaging time required. The lack of ionizing radiations at the commonly used magnetic field strengths, makes MR the most accurate imaging modality in neuropediatrics and in obstetrics. Fast imaging modalities will simplify the practical management of such patients.

Correct cephalic orientation is required in all cases to permit suitable comparative anatomical evaluations and morphometric studies. The neuro-ocular plane (NOP) is the one adopted as the reference horizontal plane. The fixity o,f this cephalic orientation, i.e., 7° angle negative to the anthropological baseline, is well established (Cabanis et al. 1981). A three-dimensional approach was performed in most cases. Sagittal slices best showed midline structures (corpus callosum, lamina terminalis, aqueduct, brainstem, and vermis) as well as the lateral surface of the brain with accurate topographical evaluation of cerebral sulcation and gyration. Coronal cuts allowed a close correlation with the gross neuro-pathological available data and contribute to the delineation of the ventricular system, basal ganglia, and rhinencephalon. Facial structures and the skull base were also best evaluated on sagittal and coronal slices, disclosing developmental malformations, delayed or asymmetric morphogenesis, and facial clefts.

Cephalometric studies are easily performed on the mid-sagittal cut of the head. The axial slices in the NOP orientation with both optic nerves fully comprised in a single cut, best demonstrate oculo-orbital anatomy allowing precise biometrical evaluations (Cabanis et al. 1982). In addition owing to the close parallelism of the NOP to the direction of the temporal horns and the lateral fissures, the true anatomical relationships are maintained and hence readily assessed, as shown in the related atlas of three-dimensional cross-sectional anatomy performed in the NOP cephalic orientation (Tamraz 1983; Tamraz et al. 1981, 1985).

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Results and discussion

Since the description of mongolism by Down in 1866 and the discovery in 1959 by Lejeune et al. of the existence of 47, instead of 46. chromosomes in those patients with trisomy 21 syndrome, the study of chromosomal patterns showing various aberrations led to the discovery that all these are associated with mental retardation. Unfortunately, the reported anatomical studies of patients with chromosomal aberrations are not numerous. This is due mainly to the high mortality of these infants, the difficulty in obtaining the parents' permission to perform brain autopsy, and the avoidence of using radiological techniques such as pneumoencephalography and/ or ventriculography, because of the invasiveness without any therapeutic benefit. Magnetic resonance imaging is the most impressive and accurate morphological in vivo technique to evaluate non-invasively, the anatomical expression of these developmental diseases. Another advantage of this technique is its ability to evaluate disorders of myelination and/or gyration due to its very high grey-white matter contrast, and atrophic changes without any artifactual modifications in shape and volume of the brains which do occur after fixation in formalin. Thus, the increasing morphological studies well correlated with clinical findings and genetic activity will help to better understand genetic disorders as well as inborn errors of metabolism. MR sensitivity and efficiency in this field will hopefully be demonstrated here.

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Patients with trisomy 21 syndrome (1-7)

The karyotype studies performed in our seven patients showed trisomy of chromosome 21. The patients ranged in age from 12 years to 35 years with a mean intelligence quotient scale of 37. This is a poor representative of the psychomotor development and mental status of this clinically v/ell known population (Table 1). Clinical signs of premature senility occur in middle-aged mongols, and senile dementia of the Alzheimer type was clinically diagnosed in patient 5. The main morphological MR findings disclosed in these patients and summarized in Tables 3 and 4 showed very similar results to those reported in the neuropathological and neuroradiological literature. There is a consistent and nearly constant hyper-brachycephaly (6/7) with shortening of the anterior segment of the skull base (6/7). The globular shape of the brain is very characteristic, with similar antero-posterior and bitemporal maximal diameters (Fig. 1a.b). The mean length and width of the seven brains as measured on MR sagittal and frontal cuts are 20.5cm (19-22 cm) and 18.5cm (16-22 cm) respectively. The increase in the sphenoid angle of the basicranium and/or delayed maturation of the sphenoid bone (5/7), is also well shown (Fig.2c), as demonstrated on previous cephalometric studies of the skull base (Alonso Tasso et al. 1985; Benda 1948; Burtwood et al. 1973; Roche et al. 1972).

Table- 4. Morphological findings in patients with trisomy 21 syndromes: brain and spinal cord. M, Mean; biT, bi temporal diameter; FO, fronto-occipital diameter
MR features and findingsPatients no.
123456
Short and rounded aspect of brain+++---
Narrowness of superior temporal gyrusL+B+B+L+L+R+
Reduced antero-posterior diameter of frontal lobes++++++
Small cerebellum-+++--
Small brainstem (pons)-+++++
Brain atrophy-++-+-
Forward bending of brainstem longitudinal axis++/-+++/--
Rectitude of cervical spinal cord+-++±-
Flat occipital contour++/-+++/-+
Simian organization of the brain (NOP)++/-++++/-
Maximum bitemporal diameter M = 18.5181818181916
Maximum fronto-occipital diameter M = 20.5192219212221
Brain indices = biT/FO x 100958695867686

Perhaps the most impressive and recognizable pattern of growth disorder of the craniofacial complex and spine in trisomy 21 is the one readily assessed on the mid-sagittal MR cut (Fig.2c-f). This highly characteristic lateral cranial silhouette frequently associated with a marked rectitude of the cervical spine (4/7 cases) and subsequently of the spinal cord, contrasted with the anteroposterior obliquity with forward bending of the longitudinal axis of the brainstem (5/7). This developmental change is rarely encountered in the normal population, even if it is more frequently noticed in early child-hood. Moreover, this apparent infantile mongol skull and brain shows a close correlation with the simian cephalic organization as demonstrated by computerized tomography using the neuro-ocular plane (Saban et al. 1983). However, more correlative and comparative cephalometric studies in a larger series need to be performed to confirm these preliminary antropometric results. Evaluation of corresponding cephalic indices might also be necessary.

Other brain malformations easily evaluated with MR and already known include conspicuous small cerebellum (4/7) and brainstem, particularly the pons (6/7) in comparison with the cerebral hemispheres (Atsushi et al. 1984; Crome et al. 1966; Davidoff 1928). Enlargement of the cisterna magna and prepontine cistern was noted in four cases and an arachnoïd cyst of the posterior fossa in one of them. Another peculiar trait of the mongol brain is the pour development of one (4/7) or both (3/7) superior temporal gyri with their narrow shape (7/7) well shown on the lateral sagittal or frontal slices (Figs. 1d and 3b), and considered by neuropathologist as one of the most characteristic developmental abnormalities found bilaterally in nearly half the patients with Down syndrome (Davidoff 1928; Friede 1975; Bersu 1980).

Hypogenesis with maldevelopment of the temporal poles and internal temporal gyri were demonstrated in patient 7 (Fig. 5). Brain atrophy was noted in four patients, two of then being 12 and 25 years old with a low IQ (27 and 39 respectively). This was not true in patient 5 with Alzheimer disease at 35 years old. Difficulty encountered in the evaluation o subtle brain atrophy and its correlation with mental retardation as with deterioration, is well known and hence shouh favor the morphometric approach as adopted by some author (Duyckaertz et al. 1985; Hubbard and Anderson 1981) using coronal sections of the brain of patients with senile deme of the Alzheimer type. Measuring cortical length and/or surface of the temporal lobes (25 bis) may help to quantify cerebral modifications in mentally retarded patients and particularly those with trisomy 21 known to show temporal lobe girls abnormalities and a disposition to develop Alzheimer disease at an early age with typical plaques and manifestations of senile tangles. The studies of frontal lobes demonstrate a reduction of the antero-posterior diameter (7/7) and in some cases hypodevelopment of the inferior frontal gyrus and subsequently a widening of the lateral fissure. Anatomo-clinical correlations and findings (Fig. 4) might be of interest and may lead to a better understanding and evaluation of mentally retarded patients or demented patients using MR.


Fig.1a-d. Patient 1 (trisomy 21 syndrome), a, b Frontal cuts using in version-recovery pulse sequence showing no gross cortical abnormalities but a characteristic rounded appearance of the brain, c Normal axial cut in the NOP. d Narrowing of the superior temporal gyrus. Fig.2a-f. Patient 3 (trisomy 21 syndrome), a Simian organization the brain with NOP plane passing through the pons and cerebellun: instead of mesencephalon and ambient cistern, b Axial cut passhu through the cranio-cervical junction and showing a dehiscence of anterior arch of C1 with hypoplastic odontoid process, c Marked forward bending of the longitudinal axis of the brainstem; shortening : the anteroposterior length of the frontal lobe; increased sphenoida angle of the basi-cranium. d Orthogonality of NOP orientation as K the direction of cervical cord instead of brainsiem. e.f Straightens cervical spine and cord with flat neck; increased cervical angle; smal cerebellum and wide cisterna magna; on sagittal surface coil images. Fig.3a-d. Patient 6 (trisomy 21 syndrome). a Lymphangiornn of tongue, b Narrow anterior portion of the first temporal gyrus. Normal axial cuts in the NOP orientation and at the ventricular with no gross abnormalities of the cortical mantle but reduced for lobes and hemispheric white matter. Fig. 4a,b. Patient 5 (trisomy 21 syndrome), a, b First and second of a T2 weighted sequence showing an abnormally signal or internal temporal gyri. Fig.5a,b. Patient 7 (trisomy 21 syndrome) a Abnormal development of the internal aspect of the temporal lobe. b Widening of the insulae

Table 5. Morphological MR findings in patients with trisomy 13 (8) and trisomy 18 (9) syndromes
Case no.Skull and faceEye and brain
8MicrocephalyAgenesis of corpus callosum
Sloping foreheadDandy-Walker variant
MicroretrognathiaHypoplasia of inferior vermis
Microphthalmos
9DolichocephalyMarked antero-posterior development of temporo-occipital lobes
Prominent occiputMild form oflobar holoprosencephaly
HypertelorismVentricular dilation
MicrognathiaHypoplasia of cerebellum
Arachnoid cyst of posterior fossa

Table 6. Morphological MR findings in patients with deletion syndromes: 4p- (10), 5p- (11) and 7p- (12)
Case no.Skull and faceEye and brain
10MicrocephalyAgenesis of corpus callosum
PlagiocephalyVentricular dilation with colpocephaly
Prominent occiputDiffuse cerebral atrophy
MicroretrognathiaProminent occipital lobe
High arched palateRight microphthalmos
Hypoplastic orbits
Hypertelorism
11MicrocephalySmall brainstem and cerebellum with ectopic tonsils
Micrognathia with prominent chinMild diffuse atrophy
Hypertelorism
Widening of nasal bridge and protruded medio-frontal region
12BrachycephalyModerate cerebral atrophy
Cleft palateAbnormal situation I. Carotid A

Finally other pathological findings were demonstrated in two of the patients. One of them (patient 6) had a distressing lymphangioma of the tongue (Fig.3a) which posterior exten-sion evaluated with MR and the other (patient 3) a malformation of the cranio-cervical junction associated with a spina bifida occulta (Fig. 2b) at levels C1, C5, and C6 of the cervical spine. This spinal malformation consisted of a rotatory at-lanto-axial subluxation with anomalies of the first and second cervical vertebrae. These comprised a cleft of the anterior arch of C1 apparantly associated with an ossiculum terminate, without any subsequent spinal cord compression demonstrated on sagittal or transverse MR slices performed using surface coils. Atlanto-axial subluxations in children due to vertebral anomalies is a rare condition. Its occurrence in trisomy 21 syndrome is much more frequent even if it is frequently asymptomatic as discovered in 20% of these patients (Martel and Tishler 1966).

Since trisomy 21 patients are mentally retarded, neurological signs or symptoms, even pain may not be recognized or evoqued. Hence, any new complaint or attitude should be considered to rule out or prevent a spinal cord compression.

In these circumstances MR ought to be the non-invasive modality of choice replacing myelography.

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Patients with other duplication (8-9) and deletion syndromes (10-12)

The morphological MR findings of the skull and the brain as demonstrated in these five patients are listed in Tables 5 and 6. The visceral malformations found in each case are also reported.

More than 100 and 150 cases of trisomy 13 and 18 respectively, have been published and the malformations reported have been collected by Bocquet (1968), Lafourcade et al. (1965), Norman (1966), Taylor (1968), Hoepner and Yanoff (1972), Huggert (1966), Keith (1966), Lafourcade et al. (1964). Alien et al. (1977), Bersu and Ramirez-Castro (1977), Cogan and Kubara (1964). Cerebral malformations were more frequently noted in Patau et al. (1960) (86%) than in Edwards et al. (1960) syndrome (23%) being mainly represented by holoprosencephaly, microcephaly, and microphthamus, or even anophthalmus (Saraux et al. 1964), but also agenesis of corpus callosum, cerebellar anomalies, and hydrocephalus. Our patient 8 with trisomy 13 had a mild form of the dysraphic state with agenesis of the corpus callosum associated with a Dandy-Walker variant (Fig. 6), Microcephaly and microphthalmia were also present, as well as the recognizable profile with the sloping forehead and the microretrognatism but no cleft palate. If holoprosencephaly is the most frequent (Miller et al. 1963) neuropathologic manifestation of this syndrome, it has been reported once in trisomy 18. Few anomalies are noted including mainly disorders of sulcation, anomalies of the corpus callosum and/or cerebral falx, hydrocephalus, and small cerebellum (Lafourcade et al. 1965; Norman 1966; Sumi 1970; Yanoff et al. 1970).


Fig.6a-d. Patient 3 (trisomy 13 syndrome). a, b A.genesis of corpus callosum. c Dandy walker variant. d Microretrognathia. Fig.7a-f. Patient 9 (trisomy 18 syndrome), a Absence of septum pellucidum. b Small cerebellum. c Arachnoid cyst of the vermian flumen. d, e Marked dolichocephaly with hypertelorism. f Ventricular dilation

Cardiac malformations known to occur in 77% of the cases of trisomy 13 were also found in patient 8 who had a severe and life-threatening hypoplasia of the left heart and ascending aorta. This infant died aged 11 days. MR exploration of our patient 9 (Fig. 7) with trisomy 18 demonstrated a small cerebellum with hypoplasia of the left hemisphere and an arachnoid cyst of the posterior fossa developed mainly in the supravermian cistern. A mild form of lobar holoprosencephaly with agenesis of the interventricular septum, hypoplasia of corpus callosum, and ventricular dilation with flattened and fused roofs of frontal horns, was also demonstrated. Dolichocephaly with prominent occiput was striking as well as the marked anteroposterior development of the temporo-occipital lobes, as compared with the relative shortening of the anterior segment.

Chromosome deletion syndromes have been recently the subject of an exhaustive review by Rethoré (1977), with special emphasis on the phenotypic and chromosomal features as well as the congenital malformations encountered. There are very few data concerning central nervous system and eye malformations in Wolf syndrome. Less than 10 observations were reported showing various brain malformations including hydrocephalus, midline defects, cerebellar anomalies, and disorders of gyration. Eye malformations were present in about one third of the cases (mainly colobomas of the Iris). Facial closure defects comprising harelip and/or cleft palate, recorded in nearly half the cases, were not demonstrated in our patient 10 presenting with only a deep and narrow philtrum. A microretrognathia with a high arched palate was obviously shown clinically as on sagittal MR cuts. A cranium bifidum a minima without any scalp defect characterized the microcephaly. Even the brain showed a dysraphic state being an agenesis of the corpus callosum associated with other disorders of morphogenesis such as a posterior ventricular dilation (Fig. 8).


Fig.8a-d. Patient 10 (4p- syndrome), a High arched palate without cleft palate, b Right microphthalmos in the NOP. c, d Agenesis of corpus callosum

As in the case of 4p- syndrome, cerebral malformations were recorded in very few patients with partial monosomy of the short arm of chromosome 5, i.e., the "cri du chat" syndrome as described by Lejeune et al. (1963, 1964). Twenty authors only mentioned brain abnormalities as demonstrated from autopsy or pneumoencephalography studies. These include cerebral and cerebellar atrophy, hydrocephalus, and ventricular dilation, and partial or complete agenesis of corpus callosum in 2 unpublished cases of the Institut of Progénèse. Various anomalies of the eyes and optic nerves may also be present as listed in the extensive review of this syndrome by Rethoré (1977).

A few consistent gross abnormalities were seen in our patient 11. These include a mild and diffuse cerebral atrophy with a small cerebellum and relatively low-set cerebellar tonsils. Protrusion of the medio-frontal region at the level of the metopic suture and widening of the nasal bridge with prominent glabella helped to describe a striking Greek profile on MR mid-sagittal slices, contrasting with the relatively poor development of the inferior facial level. Finally, excluding the cleft palate and the marked and diffuse cerebral atrophy no gross facial or cerebral malformations were noted on the MR examination of patient 12, who had a partial deletion of the short arm of chromosome 7.

More anatomical data need to be collected to evaluate more accurately the real frequency of central nervous system malformations and the craniofacial dysmorphic features that may help to suspect them. Thus, using MR our knowledge about disorders of morphogenesis as related to particular chromosomal syndromes may contribute to a better understanding of the neuropathological basis of mental retardation and its genetic basis. The importance of this non-invasive new imaging modality ought to be emphasized particularly in such patients because of their early death and the frequent difficulty in obtaining autopsy studies.


Fig. 9 a-f. Normal volunteers (30 years old), a Axial cut (using a 0.5 Testa magnet) in the neuro-ocular plane comprising the eyes and the intra-orbital optic nerves, the mesencephalon, the upper part of the culmen cerebelli, and the occipital lobes, intracranially. Compare with patient 3 (trisomy 21; Fig.2a) in the same cephalic orientation. b Mid-sagittal cut (using a 0.5 Testa magnet) showing the usual orientation of the brainstem onto the direction of the cervical cord. Compare with patient 3 (trisomy 21; Fig.2c) in the same cephalic posture. c Lateral aspect of the brain (using a 0.5 Tesla magnet) showing the temporal gyri and the cortical architecture of the hemispheres. Compare with the relative narrowing of the superior temporal gyrus in some of the patients with trisomy 21 syndrome (see Figs. 1d, 3b). d Normal lordosis of the cervical spine and cord in the sagittal plane (using a 0.15 Tesla magnet). Compare with the rectitude of the neck of the patients with trisomy 21 syndrome (see Fig. 1f), e Cervical spine and cord of a normal volunteer in a dynamic maneuver with a hyper-extended (e) and a hyperflexcd attitude (f). Compare the hyperflexed attitude showing a straightening of the cervical spine and cord, with the similar usual indifferent cervical posture of patients with trisomy 21 syndrome (Fig.2f)


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