Haut
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 reportsHaut
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. | Patients | Age
(years) | Karyotypes | Height (m) | Weight (kg) | H.C.
(cm) | IQ |
1 | BOU. N.
(995) | 18 | 47,XX,+21 | 1.34 | 36 | 49 | 42 |
2 | LAR.S.
(424) | 35 | 47,XX,+21 | 1.46 | 54 | 53 | 34 |
3 | GAU.V.
(775) | 25 | 47,XX,+21 | 1.46 | 48 | 50 | 39 |
4 | DUF.A.
(305) | 20 | 47,XX,+21 | 1.52 | 45 | 52 | 57 |
5 | SEV.R.
(996) | 35 | 47,XX,+21 | 1.42 | 52 | 50 | 21 |
6 | BOU.E.
(987) | 12 | 47,XY,+21 | 1.27 | 26 | 52 | 27 |
7 | PAS.F.
(1121) | 32 | 47,XY,+21 | 1.61 | 66 | 53 | 40 |
Table 2. Patients with duplication (8-9) or deletion (10-12)
syndromes
Case
no. | Patients | Age | Karyotype | Height
(m) | Weight (kg) | H.C. (cm) | IQ |
8 | LEV. C. (905) | 6
days | 47,XX,+13 | 0.48 | 2.65 | 32 | - |
9 | PER. A. (463) | 2.5
months | 47,XX,+18 | 0.46 | 2.35 | 35.5 | - |
10 | NOC.M. (107) | 2
months | 46,XX,del(4p) | 0.47 | 2.15 | 32 | - |
11 | HAC.H. (1925) | 26
years | 46,XX,del(5p) | 1.50 | 56 | 52.5 | 55 |
12 | TIS.M. (917) | 27
years | 46,XX,del(7)(p12) | 1.57 | 34 | 51 | 30 |
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 findings | Patients no. |
1 | 2 | 3 | 4 | 5 | 6 | 7 |
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 findings | Patients no. |
1 | 2 | 3 | 4 | 5 | 6 |
Short and rounded aspect of
brain | + | + | + | - | - | - |
Narrowness of superior temporal
gyrus | L+ | 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 =
18.5 | 18 | 18 | 18 | 18 | 19 | 16 |
Maximum fronto-occipital diameter M =
20.5 | 19 | 22 | 19 | 21 | 22 | 21 |
Brain indices = biT/FO x
100 | 95 | 86 | 95 | 86 | 76 | 86 |
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 face | Eye and brain |
8 | Microcephaly | Agenesis of
corpus callosum |
Sloping forehead | Dandy-Walker variant |
Microretrognathia | Hypoplasia of inferior
vermis |
| Microphthalmos |
9 | Dolichocephaly | Marked
antero-posterior development of temporo-occipital lobes |
Prominent occiput | Mild form oflobar
holoprosencephaly |
Hypertelorism | Ventricular dilation |
Micrognathia | Hypoplasia 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 face | Eye and brain |
10 | Microcephaly | Agenesis of
corpus callosum |
Plagiocephaly | Ventricular dilation with
colpocephaly |
Prominent occiput | Diffuse cerebral atrophy |
Microretrognathia | Prominent occipital lobe |
High arched palate | Right microphthalmos |
Hypoplastic orbits | |
Hypertelorism | |
11 | Microcephaly | Small brainstem
and cerebellum with ectopic tonsils |
Micrognathia with prominent chin | Mild diffuse
atrophy |
Hypertelorism | |
Widening of nasal bridge and protruded medio-frontal
region | |
12 | Brachycephaly | Moderate
cerebral atrophy |
Cleft palate | Abnormal 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.
Haut
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)
Haut
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