May 31, 1991 - ventricles and septum pellucidum, men- tal retardation ... There was a shawl scrotum. Neuro- ... enlarged ventricles anda cyst in the septum.
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I Med Genet 1992; 29: 497-499
Cerebrofaciothoracic dysplasia: a new family N Philip, A Guala, A Moncla, M Monlouis, S Ayme, F Giraud
Abstract We describe two brothers, born to consanguineous parents, who had facial dysmorphism, complex anomalies of the vertebrae and ribs, enlarged cerebral ventricles and septum pellucidum, mental retardation, and affable behaviour. The features are similar to those previously described in three unrelated children and may represent new cases of
cerebrofaciothoracic dysplasia. In 1975, Pascual-Castroviejo et all described a multiple congenital anomaly/mental retardation syndrome in three unrelated children. This syndrome consisted of facial dysmorphism, multiple malformations of the vertebrae and ribs, and mental retardation and was named cerebrofaciothoracic dysplasia. Parental consanguinity in two of the three families prompted the authors to suggest autosomal recessive inheritance. In the present report we described a new family in which two sibs exhibit the main characteristic features of cerebrofaciothoracic dysplasia. In the second case, the diagnosis was suspected during pregnancy on ultrasound scan, indicating that prenatal diagnosis of this recessive condition is possible.
Centre de Gen6tique Medicale et INSERM U 242, H6pital d'Enfants de la Timone, 13385 Marseille Cedex 5, France. N Philip A Moncla S Ayme F Giraud
Servicio Di Genetica Clinica, Instituto di Discipline Pediatriche, Universita di Torino, Italy. A Guala
Service de Pediatrie, Centre Hospitalier Intercommunal D'Aubagne, France. M Monlouis Correspondence to
Dr Philip. Received 31 May 1991. Revised version accepted 6 November 1991.
Case reports Both parents are healthy. The father, born in 1953, and the mother, born in 1950, are second cousins and come from Morocco. The couple had five pregnancies before the probands: two spontaneous miscarriages, two healthy girls, and a multiple malformed child who died at 15 days in Morocco. Case 1 was born in 1989 by caesarian section in the 41st week of a pregnancy complicated by polyhydramnios during the third trimester. Birth weight was 3800 g (75th centile), length 52-5 cm (75th centile), and head circumference 39 cm (> 97th centile). The baby had a right cleft lip and palate which was surgically repaired at 3 months of age. At this time, chromosomal analysis was performed because of facial dysmorphism and showed a normal 46,XY karyotype. Surgery for inguinal hemia was performed at 5 months. Transfontanellar echography and CT scan of the head showed enlarged ventricles and a cyst in the septum pellucidum. At 14 months of age, the couple were referred to the centre for medical genetics with their child for clinical advice as the mother was 26 weeks pregnant. On examination the child had short stature (73 cm, < 3rd centile), weight 9 5 kg (10th centile), and macrocephaly
(OFC 50 cm 90th to 97th centile) with brachycephaly. The face was unusual (fig 1) with bitemporal narrowing, frontal whorl, hypertelorism, large root of the nose, large mouth with scar of repaired cleft lip, low set and posteriorly rotated ears, and micrognathia. The neck was short. There was a shawl scrotum. Neurological evaluation showed hypotonia, delayed psychomotor development, and an affable character. On radiography (fig 2), the first ribs were short bilaterally. Bony bridges joined the posterior arches of ribs 2 and 3 (left and right), 1 and 2, 4 and 5, and 6 and 7 (left), and 7 and 8 (right). Some ribs were bifid (2 right, 7 and 9 left). There were also hemivertebrae and wedged vertebrae in the lower cervical and thoracic regions. The couple were counselled about a possible autosomal recessive condition with a 25% recurrence risk. Currently, at 27 months of age, psychomotor retardation is obvious. The child is unable to stand or walk and has no speech. Sitting was achieved at 26 months. Case 2 is the seventh pregnancy of the couple in 1990. A first ultrasound scan was performed at 26 weeks of gestation and showed polyhydramnios. Ammiocentesis at 29 weeks showed a normal 46,XY karyotype and normal amniotic fluid a fetoprotein. At 32 weeks the polyhydramnios had worsened and there were
Figure 1 Case 1, facial dysmorphism.
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Philip, Guala, Moncla, Monlouis, Ayme, Giraud
arches of the vertebrae, similar to those observed in the older brother. Diaphyseal bone length ratios were compared with standard values,2 giving the following results: radius/humerus 0-82 (mean), tibia/femur 0 86 (+ 2 SD), humerus/femur 0-83 (mean), radius/ tibia 0-78 (- 1 SD).
Figure 2 Radiograph of the chest of case 1.
cerebral abnormalities consisting of moderately dilated lateral ventricles and enlarged septum pellucidum. The parents were informed and elected to continue the pregnancy at this stage. Caesarian section was performed at 35 weeks' gestation. Birth weight was 3660 g (90th centile), length 50 cm (75th centile), and OFC 38 cm (> 97th centile). The baby exhibited dysmorphic features (fig 3) including frontal hirsutism, antimongoloid slant of the eyes, hypertelorism, epicanthus, and low set and posteriorly rotated ears. The neck was short with a low posterior hair line. There was a sacral dimple and normal male genitalia. Brain CT scan confirmed the enlargement of the septum pellucidum and showed a hypoplastic corpus callosum and enlarged ventricles. Radiographs of the chest showed complex malformations with fused and bifid ribs, hemivertebrae, and fusion of the posterior
."ift
Figure 3 Case 2, facial dysmorphism.
Discussion The two sibs described above showed abnormal costovertebral abnormalities consistent with a spondylocostal dysostosis (SCD). The autosomal recessive form of SCD is the most common and there is wide clinical inter- and intrafamilial variability.3 Associated malformations, mostly midline defects and facial dysmorphism, have been described.4 Mental retardation, however, is not a feature of typical SCD and our two patients are likely to have a distinct condition. Distinct genetic syndromes including costovertebral dyssegmentation and other malformations have been delineated and three of them can be discussed here. The cerebrofaciothoracic dysplasia described in 1975 in three unrelated patients by Pascual-Castroviejo et all shares many clinical features with the two boys described in this paper, as shown in the table. Costovertebral defects are identical in all five patients. They include bifid ribs, hemivertebrae, and a peculiar form of costal synostosis consisting of the formation of bony bridges between the posterior arches of the ribs. Vertebral defects are limited to the upper part of the spine. Macrocrania was present in one patient of Pascual-Castroviejo et all and brachycephaly in the other two. Both our patients had macrocephaly, one with brachycephaly. Facial dysmorphism is very similar and includes epicanthus, hypertelorism, broad and short nose, low set ears, flat profile, and short neck with low posterior hair line. Intracranial defects were present in four patients: the septum pellucidum was large in two patients and cystic in another, and two patients had hypoplasia of the corpus callosum, one with a large septum pellucidum. Other malformations have been described, such as hernia (3/5). Psychomotor development is impaired in all cases recorded. Of noticeable interest is the presence of affable behaviour in all the patients who are said to be friendly and have good social contact in spite of their mental retardation. Although very similar to the cases described by PascualCastroviejo et all our two patients showed slight differences. Polyhydrammios complicated both pregnancies, macrocrania was present at birth in our two patients, and one of them had cleft lip and palate. Conversely, calcification of the interclinoid ligament, described as a constant feature of the former patients, was absent in our two cases. Prenatal diagnosis of this autosomal recessive condition is possible. Intracranial defects can be used as prenatal sonographic markers but the diagnosis may be late in pregnancy, as illustrated by the present case 2. Autosomal recessive Robinow syndrome could also be a possibility.5 Dysmorphism is similar to that
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Cerebrofaciothoracic dysplasia: a new family Clinical features of the five reported cases of cerebrofaciothoracic dysplasia.
Pascual-Castroviejo et al' 3y 5y 7j y + + + ++ + + +
Age of patients Consanguinity Polyhydramnios Mental retardation Affable character
Morphological Macrocephaly Brachycephaly Low hair line Narrow forehead Synophrys Epicanthus Hypertelorism Low set ears Flat face Short neck Cleft lip/palate Raised scapulae Narrow thorax Inguinal hernia Sinus pilonidalis
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Radiographical Calcification interclinoid ligament Septum pellucidum anomaly Hypoplastic corpus callosum Costovertebral defects
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Present report 3d 14 m
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described in the two brothers but many features are diiscordant, notably the normal genitalia in the two sibs, except for a shawl scrotum in pat ient 1. The normality of limb bone length rat:ios in patient 2 is also a strong argument again st this diagnosis. Also, patients with Robinow syndrome usually have normal intelligence.
In 1985, Moerman et al6 described a new syndrome with spondylocostal anomalies, macrocrania, and intracranial malformations such as hydrocephalus, Dandy-Walker malformation, and agenesis of the corpus callosum, congenital heart defect, renal defect, and dwarfism. This condition is lethal and seems to be very different from that of the two patients described here. In conclusion, cerebrofaciothoracic dysplasia appears to be a distinct entity. This multiple malformation syndrome has an autosomal recessive pattern of inheritance as proven by the parental consanguinity and the recurrence in the same sibship. Prenatal diagnosis is possible by careful ultrasonographic monitoring of pregnancy in search of macrocrania, abnormalities of the septum pellucidum, polyhydramnios, and vertebral anomalies. Pascual-Castroviejo I, Santoyala JM, Lopez-Martin V, Rodriguez-Costa T, Tendero A, Mulas F. Cerebro-faciothoracic dysplasia: report of three cases. Dev Med Child Neurol 1975;17:343-51. 2 Robinow M, Chumley W. Standard for limb bone length ratios in children. Radiology 1982;143:433-6. 3 Ayme S, Preus M. Spondylocostal/spondylothoracic dysos1
tosis: the clinical basisGenet for prognosticating Am J Med 1986;24:599-606.and genetic counseling. 4 Casamassima AC, Casson Morton C, Nance WE, et al. Spondylocostal dysostosis associated with anal and urogenital anomalies in a Memonite sibship. Am J Med Genet
1981;8:117-27.
5 Teebi Autosomal recessive Robinow syndrome. Am J Med A. Genet 1980;35:64--8.
6 Moerman P, Vandenberghe K, Fryns JP, Haspelagh M,
Lauweryns JM. A new lethal chondrodysplasia with spon-
dylocostal dysostosis, multiple internal anomalies and Dandy-Walker cyst. Clin Genet 1985;27:160-4.
