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Cerebro-Costo-Mandibular Syndrome

Cerebrocostomandibular Syndrome

Cerebro-costo-mandibular syndrome is a very rare genetic disorder in which mutations in the small nuclear ribonucleoprotein polypeptides B and B1 (SNRPB) genes cause various skeletal anomalies of the thorax and spine. The diagnosis is made based on clinical criteria and the prognosis depends on the severity of defects and associated complications, most important being frequent upper respiratory tract infections.


Presentation

Cerebro-Costo-Mandibular syndrome (CCMS) is presumably inherited through an autosomal dominant mode (although sporadic cases have been identified). This means that symptoms are almost universally seen in the setting of a positive family history. They can commence soon after birth, but the majority of cases are diagnosed during infancy or childhood [1] [2]. The cardinal features of CCMS are:

  • Facial changes - Normal development of the palate may be impaired due to insufficient growth of the mandible during fetal life, leading to an abnormally positioned tongue and an underdeveloped mandible (known as micrognathia) that is evident on physical examination [2] [3]. Furthermore, a cleft palate and feeding difficulties are frequently noted [1], and the term "Pierre Robin sequence" is frequently used to describe facial and mandibular features seen in this syndrome [2].
  • Defects of the thorax and spine - "rib-gap syndrome" is a synonym for CCMS, the primary reason being the appearance of bilateral multiple posterior rib gaps (most frequently between the 4th and 10th ribs) that are often misidentified as rib fractures [4] [5] [6]. As a result, pulmonary function is significantly reduced. Together with scoliosis and laryngotracheal abnormalities and other prominent findings in CCMS patients, they predispose to profound respiratory obstruction and frequent respiratory tract infections. They are the most important cause of early death. Mortality rates range from 35-50% in the first year of life in the absence of the correct diagnosis and proper management [4] [5]. Blockade of the nasal passage (choanal atresia) may also be encountered, further contributing to the respiratory pathology [5].
  • Cranial abnormalities - A very small head circumference with severe microcephaly, as well as mental retardation, is observed in a minority of patients, with the extent of brain damage depending on the time of diagnosis [1] [3] [5].
  • Miscellaneous findings - Congenital heart disease (septal defects), a horseshoe kidney, hearing loss, hypoplasia of the elbows and the clavicle and hypospadias are other notable findings in CCMS [1] [2].
Pathologist
  • Pediatricians, surgeons, physicians who diagnose and treat abnormalities of the lungs (pulmonologists), specialists who assess and treat hearing problems (audiologists), speech pathologists, and other health care professionals may need to work together[rarediseases.org]
Hypoxemia
  • Early diagnosis of this rare syndrome can lead to early intervention in the respiratory tract that could avoid the cerebral effects of prolonged hypoxemia. Footnotes Published: August 29, 2011 References 1. Smith DW, Theiler K, Schachenmann G.[ncbi.nlm.nih.gov]
Normal Hearing
  • Conductive hearing loss occurs in about two thirds (67%) of people with CCMS, where problems in how the ears are formed prevents normal hearing.[rarediseases.org]
Hearing Impairment
  • The patient had a history of congenital hearing impairment and craniofacial anomalies at birth. At the same time, ocular anomalies were discovered [Figure 1]. At the age of 2 years, he underwent a corrective surgery of the lip palate.[advbiores.net]
Narrow, Bell-Shaped Thorax
  • Chest X-ray on the first day of life showed a narrow, bell-shaped thorax with eleven pairs of ribs, with posterior rib-gap defects of the second to ninth rib on both sides (Figure 1a).[docplayer.net]
Narrow, Bell-Shaped Thorax
  • Chest X-ray on the first day of life showed a narrow, bell-shaped thorax with eleven pairs of ribs, with posterior rib-gap defects of the second to ninth rib on both sides (Figure 1a).[docplayer.net]
Psychomotor Retardation
  • Cerebro-costo-mandibular syndrome is a rare disorder characterized by psychomotor retardation, posterior rib-gap defects, and the orofacial defects of Pierre Robin sequence.[ncbi.nlm.nih.gov]
  • Psychomotor retardation, which hasbeen described in almost one-half of CCMS cases, is anothercontroversial nding of CCMS.1 It is thought to be the resultof perinatal and postnatal hypoxia, although cerebralndings of the reported cases do not support this[documents.tips]
  • 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[datospdf.com]
  • This may support the hypothesis that psychomotor retardation is most likely secondary induced. Meineke et al. [1987] suggested al- ready that costo-mandibular syndrome might be a bet- ter designation than CCMS.[docslide.com.br]

Workup

The diagnosis of CCMS may not be easy, as less than 100 cases have been described in the literature [2] [5]. Nevertheless, a detailed patient history regarding the onset of symptoms and a thorough physical examination can provide sufficient data to raise clinical suspicion. The presence of micrognathia and respiratory difficulties necessitate the use of imaging studies, such as plain radiography, computed tomography (CT) or magnetic resonance imaging (MRI). Chest X-rays will reveal a narrow or bell-shaped thorax and bilateral multiple posterior rib gaps, while mandibular hypoplasia can be confirmed using either X-rays or CT [1] [2] [6]. Radiography may be employed if hypoplasia of other skeletal structures (extremities or the clavicles) is suspected as well, whereas cardiac and renal structures should be evaluated by CT or MRI. Additionally, endocranial imaging (preferably MRI) is advocated, particularly if signs of mental retardation exist [2]. Some reports suggest that a prenatal diagnosis of CCMS can be made using fetal ultrasonography and identifying thoracic, facial abnormalities and increased nuchal translucency [6].

Treatment

  • A case is reported in which vigorous treatment permitted survival. Serial roentgenograms subsequently demonstrated a progressive diminution of the characteristic posterior rib-gap defects.[ncbi.nlm.nih.gov]
  • A boy, having a mother with Pierre-Robin sequence and a sister with CCMS, was diagnosed prenatally with CCMS and successfully treated with ex utero intrapartum treatment (EXIT) at 36 weeks 6 days of gestation.[ncbi.nlm.nih.gov]
  • Treatment - Cerebro-costo-mandibular syndrome Treatment and prognosis depend on the features and severity in each affected person. Resources - Cerebro-costo-mandibular syndrome[checkorphan.org]
  • Standard Therapies Treatment The treatment of CCMS is based on the symptoms that a person with CCMS has. Treatment may require a group effort from a team of specialists.[rarediseases.org]

Prognosis

  • CCMS can be classified into three categories--lethal, severe, and mild--according to the severity of the symptoms and prognosis.[ncbi.nlm.nih.gov]
  • The diagnosis is very often made at birth and the prognosis is very poor. Antenatal ultrasound examination may show a combination of orofacial and chest maldevelopment.[ncbi.nlm.nih.gov]
  • The overall survival rate for patients with this disorder has not been reported, and a classification of the patients on the basis of the prognosis is not yet available.[semanticscholar.org]
  • Prognosis The analysis using the Kaplan–Meier method revealed that the prognosis was extremely poor ( Fig. 3A ).[onlinelibrary.wiley.com]
  • Prognosis - Cerebro-costo-mandibular syndrome Not supplied. Treatment - Cerebro-costo-mandibular syndrome Treatment and prognosis depend on the features and severity in each affected person. Resources - Cerebro-costo-mandibular syndrome[checkorphan.org]

Etiology

  • Elsevier Health Sciences, ١٨‏/٠٨‏/٢٠١٣ - 979 من الصفحات Smith’s Recognizable Patterns of Human Malformation has long been known as the source to consult on multiple malformation syndromes of environmental and genetic etiology as well as recognizable disorders[books.google.com]
  • Although several hereditary cases have been reported, the true etiology is unknown. We describe a patient with CCMS in whom palatoplasty was performed at 3 years 8 months. We followed up the patient until 6 years of age.[jstage.jst.go.jp]
  • Etiology No causative gene has been identified to date. It has been proposed, however, that defects in the sonic hedgehog (SHH) signaling cascade may be responsible for these developmental anomalies.[orpha.net]
  • […] interstitial and granulonodulo alveolar pattern 324 Interstitialreticular pulmonary pattern 326 Disseminated interstitial pneumonitis 327 The miliary pattern of pneumonia 328 Short linear andor wedgeshaped densities 329 Pulmonary edema in infancy and childhood Etiology[books.google.com]
  • Elsevier Health Sciences , 18 ago 2013 - 979 pagine Smith’s Recognizable Patterns of Human Malformation has long been known as the source to consult on multiple malformation syndromes of environmental and genetic etiology as well as recognizable disorders[books.google.it]

Epidemiology

  • Summary Epidemiology More than 80 cases have been reported to date; both males and females are equally affected. Clinical description CCMS is characterized by orofacial and costovertebral developmental anomalies. Severity is highly variable.[orpha.net]
  • Maric Dusan M Djan Igor Maric Dusica L Madic Dejan M Petkovic D Velickovic S Gajdobranski Djordje Info HEALTHMED, (2011), vol. 5 br. 6, Suppl. 1, str. 2183-2185 Ispravka ISI/Web of Science Elečas Rang časopisa Citati: Naslov Pediatric femur fractures, epidemiology[kobson.nb.rs]
  • Eur J Pediatr (1989) 1.00 Limb defects associated with major congenital anomalies: clinical and epidemiological study from the International Clearinghouse for Birth Defects Monitoring Systems.[pubrank.carbocation.com]
Sex distribution
Age distribution

Prevention

  • EXIT would be an effective option for rescuing patients with prenatally diagnosed CCMS and preventing neonatal hypoxia.[ncbi.nlm.nih.gov]
  • Symptoms - Cerebro-costo-mandibular syndrome Causes - Cerebro-costo-mandibular syndrome Prevention - Cerebro-costo-mandibular syndrome Not supplied. Diagnosis - Cerebro-costo-mandibular syndrome Not supplied.[checkorphan.org]
  • Management: Includes intensive care for improving neonatal respiratory function Prevention of feeding difficulties. Operative interventions - musculoskeletal, palatal or hearing problems.[medicalchemy-syndromes.blogspot.com]
  • TIS is a disorder where severe problems in how the chest, spine, and ribs are formed prevent normal breathing and lung development.[rarediseases.org]

References

Article

  1. Tooley M, Lynch D, Bernier F, Parboosingh J, Bhoj E, Zackai E, et al. Cerebro-costo-mandibular syndrome: Clinical, radiological, and genetic findings. Am J Med Genet A. 2016;170A(5):1115-1126.
  2. Abdalla W, Panigrahy A, Bartoletti SC. Cerebro-costo-mandibular syndrome: Report of two cases. Radiol Case Rep. 2011;6(3):495.
  3. Watson TA, Arthurs OJ, Muthialu N, Calder AD. Multi-detector thoracic CT findings in cerebro-costo-mandibular syndrome: rib gaps and failure of costo-vertebral separation. Skeletal Radiol. 2014;43(2):263-266.
  4. Nagasawa H, Yamamoto Y, Kohno Y. Cerebro-costo-mandibular syndrome: prognosis and proposal for classification. Congenit Anom (Kyoto). 2010;50(3):171-174.
  5. Ramaswamy P, Negus S, Homfray T, De Rooy L. Severe micrognathia with rib dysplasia: cerebro-costo-mandibular syndrome. Arch Dis Child Fetal Neonatal Ed. 2016;101(1):F85.
  6. Hosalkar HS, Shaw BA, Ceppi CL, Ng BC. The cerebro-costo-mandibular syndrome: 9-year follow-up of a case. J Postgrad Med. 2000;46:268.

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Last updated: 2019-06-28 09:30