Pediatrics International (2001) 43, 522–524
Cerebro-costo-mandibular syndrome: A case report FERDA ÖZKINAY, ÖZGÜR ÇO}ULU, CUMHUR GÜNDÜZ, TUFAN ÇANKAYA AND CIHANGIR ÖZKINAY** Department of Pediatrics, Ege University, Faculty of Medicine, Gzmir, Turkey Key words
cerebro-costo-mandibular syndrome, multiple rib abnormalities, Robin anomaly.
Cerebro-costo-mandibular syndrome (CCMS) is a rare disorder characterized by multiple rib abnormalities and Robin anomaly.1 Most cases show motor and/or mental retardation. About 50 cases have been described until now worldwide. The syndrome shows genetic heterogeneity and both familial and sporadic cases have been reported to date.2–5 Here we describe a case showing the cardinal features of CCMS. The parents were consanguineous and the mother lost three more children with similar ﬁndings. As parental consanguinity was involved and three siblings died from a similar disorder, this supports autosomal recessive inheritance mode for this syndrome.
Case report The patient was a 27-month-old male. He was referred to the Genetics Clinic because of growth and developmental retardation, micrognathia and abnormal chest shape (Figs. 1,2). His parents were ﬁrst-cousins, married to each other and the patient was born after 32 weeks of gestation. Information on his birthweight was unavailable. The mother experienced two pregnancies before this baby’s birth and two medical abortions after the birth of proband. The products of the ﬁrst pregnancy were twins and one of them had hypertelorism, micrognathia, high palate, hypotonia and died from respiratory insufﬁciency soon after birth. The third child also had similar features such as hypotonia, popliteal pterygium, pes equino-varus and died at the age of 3 days due to respiratory problems. The other two pregnancies were terminated on the parents’ willingness within the ﬁrst 2 months of pregnancy. The mother had neither genetic counseling nor ultrasonographic examination during her pregnancies.
Correspondence: Ferda Özkgnay MD, Ege University Faculty of Medicine, Department of Pediatrics, 35100 Bornova-Gzmir, Turkey. Email: [email protected]
Received 27 December 1999; revised 28 June 2000; accepted 14 July 2000.
The child has been fed poorly since birth and has been treated for respiratory problems on several occasions. His weight was 8450 g (< third centile), height was 49.5 cm (third centile) and head circumference was 49.5 cm (50th centile). On physical examination he had hypotonia, hypertelorism, depressed nasal bridge, severe micrognathia with glossoptosis, high-arched palate, low-set ears, gingival hyperthrophia, bell-shaped thorax, axillary and popliteal pterygium, dimples on the elbows and knees, pes equinovarus and cutaneous syndactyly between the second and third toes. Upper and lower extremities were in the ﬂexed position and ﬂexion contractures were developed. He started to use single words at the age of 1. At 2-years-old he could put three words together and he listened to what he was told. Now, he is cooperating with his parents very well, however, he could not sit and walk. Chest roentgenograph showed narrow and bell-shaped thorax, kyphosis, multiple dorsal rib-gap defects, undulated ribs and increased antero-posterior diameter (Fig. 3). Craniography revealed laterolateral narrowing, wormian bones and hypoplastic mandible. Cranial magnetic resonance imaging was normal. Dentinogenesis imperfecta was observed on dental examination. His karyotype was normal. During hospitalization, he was treated with antibiotics for his respiratory infection and a special diet was given for his malnutrition. Physiotherapy was planned for his limited physical function.
Discussion The association of Robin anomaly and posterior rib abnormalities appear to constitute a speciﬁc syndrome, which has been deﬁned as cerebro-costo-mandibular syndrome. About 50 cases have been described since 1966 when the syndrome was deﬁned for the ﬁrst time by Smith et al.6 Cerebral involvement is not a constant feature in this syndrome. Plötz et al. reviewed 50 cases and reported that more than one-half of the patients had no cerebral abnormality.2 Morphological
Lateral appearance of case study patient. Fig. 2 View of case study patient.
cerebral abnormalities such as small brain, porencephalic cysts, agenesis of corpus callosum, dilated lateral ventricles, gliosis and ﬁfth ventricle have been reported in several cases with CCMS.1 It has been suggested that most of the histological ﬁndings deﬁned in brain autopsies of the patients with CCMS can also be seen in severe neonatal asphyxia, which is very common in these patients.2,3 Since the cerebral changes are not a constant anomaly in this syndrome, it has been suggested that ‘costo-mandibular’ might even be a better name to deﬁne the syndrome.1 In our patient, although motor function is markedly delayed, we did not observe any cerebral abnormality with the techniques available. Psychomotor retardation, which has been described in almost one-half of CCMS cases, is another controversial ﬁnding of CCMS.1 It is thought to be the result of perinatal and postnatal hypoxia, although cerebral ﬁndings of the reported cases do not support this hypothesis. There is a wide variability of rib anomalies in CCMS patients. The severity of rib abnormalities in CCMS can vary from a few affected dorsal rib segments to complete absence of all and may not be symmetric.1 The characteristic feature of rib anomaly is posterior rib-gap and vertebral changes may also be associated with the rib abnormalities.4 The only
vertebral change seen in our patient was platyspondyly (Fig. 3). The inheritance mode of CCMS shows heterogeneity. Both autosomal dominant and recessive transmissions have been postulated. A number of cases have been reported to have parental consanguinity, whereas some others apparently show autosomal dominant transmission.2,3 Two pairs (four sibs) of twins with CCMS have been reported by Drosseou et al. which support autosomal recessive inheritance with a high predominance.7 Our case also strongly supports autosomal recessive inheritance in this syndrome because of parental consanguinity and three affected siblings. The only method using in prenatal diagnosis is ultrasonographic examination. Megier et al. reported a case with CCMS diagnosed prenatally for the ﬁrst time.8 Polyhydramnios and a very unusual shape of the ribs were documented as ultrasonographic ﬁndings of CCMS.8,9 In conclusion, CCMS shows genetic heterogeneity and different expressivity with autosomal recessive and autosomal dominant inheritance and the cause of CCMS is unknown. However, two developmental genes, myogenic factor 5 (Myf5) and goosecoid gene, which have been
F Özkgnay et al. References
X-ray of patient’s chest.
mapped to chromosome 12 and 14, respectively, have been thought to be responsible for this rare genetic disorder.10 More cases, especially families with CCMS, need to be investigated and a careful examination is necessary while genetic counseling is given.
1 Plötz FB, van Essen AJ, Bosschaart AN, Bos AP. Cerebrocosto-mandibular syndrome. Am. J. Med. Genet. 1996; 62: 286–92. 2 Leroy JG, Devos EA, Bulcke LJV, Robbe NS. Cerebro-costomandibular syndrome: A case with autosomal dominant inheritance. J. Pediatr. 1981; 99: 441–3. 3 Trautman MS, Schelley SL, Stevensor DK. Cerebro-costomandibular syndrome: A familial case consistent with autosomal recessive inheritence. J. Pediatr. 1985; 107: 990–1. 4 McNicholl B, Egan-Mitchell B, Murray JP, Doyle JF, Kennedy JD, Crome L. Cerebro-costo-mandibular syndrome. A new familial development disorder. Arch. Dis. Child. 1970; 45: 421. 5 Gürgey A, Caglar M, Topcu M, Kutluk T. A case of the cerebro-costo–mandibular syndrome. Turk. J. Pediatr. 1985; 27: 109–12. 6 Smith DW, Theiler K, Schachenmann G. Rib-gap defect with micrognathia, malformed tracheal cartilages, and redundant skin: a new pattern of defective development. J. Pediatr. 1966; 69: 799–803. 7 Drossou-Agakidou V, Andreou A, Soubassi-Griva V, Pandouraki M. Cerebro-costo-mandibular syndrome in four sibs, two pairs of twins. J. Med. Genet. 1991; 28: 704–7. 8 Megier P, Ayeva-Derman M, Esperandieu O, Aubry M, Couly G, Desroches A. Prenatal ultrasonographic diagnosis of the cerebro-costo-mandibular syndrome: case report and review of the literature. Prenat. Diagn. 1998; 18: 1294–9. 9 Merlob P, Schonfeld A, Grunebaum M, Reisner SH. Autosomal dominant cerebro-costo-mandibular syndrome: ultrasonographic and clinical ﬁndings. Am. J. Med. Genet. 1987; 26: 195–202. 10 Hennekam RC, Goldschmeding R. Complete absence of rib ossiﬁcation, micrognathia and ear anomalies: extreme expression of cerebro-costo-mandibular syndrome? Eur. J. Hum. Genet. 1998; 6: 71–4.