Cerebro‐costo‐mandibular syndrome: A case report
Makaleler > Tam Makale · 2001
Yazarlar: Feriştah Ferda ÖZKINAY, Muhsin Özgür ÇOĞULU, Cumhur GÜNDÜZ, T CANKAYA, C OZKINAY
Pediatrics International, SCI Expanded İndekslerine Giren Dergi, Uluslararası, Wos, 2001, cilt 43, ss 522-524
DOI: 10.1046/j.1442-200x.2001.01430.x
Özet
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. 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. Lateral appearance of case study patient. View of case study patient. 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. 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 equino-varus 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). X-ray of patient’s chest. 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. 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 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 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.