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].

• Feeding Difficulties

  Cleft palate, feeding difficulties, respiratory distress, tracheostomy requirement, and scoliosis are common. Additional malformations such as horseshoe kidney, hypospadias, and septal heart defect may occur. [research-information.bris.ac.uk]

  Management: Includes intensive care for improving neonatal respiratory function Prevention of feeding difficulties. Operative interventions - musculoskeletal, palatal or hearing problems. [medicalchemy-syndromes.blogspot.com]

  Furthermore, a cleft palate and feeding difficulties are frequently noted, and the term "Pierre Robin sequence" is frequently used to describe facial and mandibular features seen in this syndrome. [symptoma.com]

  Sometimes, there are associated anomalies and problems, such as spine deformities, brain, heart, kidney or ear anomalies, feeding difficulties, delayed psychomotor development, and growth impairment. [ncbi.nlm.nih.gov]

  Their origin lies in underventilation of lungs, lying position in bed, and often microaspirations because of feeding difficulties. Special 4 434 Matić A. et al. [docplayer.net]

• Developmental Disorder

  Cerebro costo - mandibular syndrome: a new familial developmental disorder. [yumpu.com]

  Cerebro-costo-mandibular Syndrome A New Familial Developmental Disorder Abstract Three sibs with a hitherto unreported syndrome are described, the main features being mental handicap, palatal defects, micrognathia, and severe costovertebral defects, involving [adc.bmj.com]

  Abstract Cerebro-costo-mandibular syndrome (CCMS) is a developmental disorder characterized by the association of Pierre Robin sequence and posterior rib defects. [ncbi.nlm.nih.gov]

  Storage Disorder... more Cerebrocostomandibular syndrome is a potentially lethal developmental disorder characterized by mental handicap, palatal defects, micrognathia, and severe costovertebral defects. [scinapse.io]

  A new familial developmental disorder. Arch Dis Chil 45: 421 Google Scholar 4. Silverman FN, Strefling AM, Stevenson DK, Lazarus J (1980) Cerebro-costo-mandibular syndrome. J Pediatr 97: 406 PubMed Google Scholar 5. [link.springer.com]

• Disability

  Journal of Developmental and Physical Disabilities 28(3), pp. 425-441. (10.1007/s10882-016-9478-0) pdf Cianfaglione, R.et al. 2016. Ageing in Rett syndrome. Journal of Intellectual Disability Research 60(2), pp. 182-190. (10.1111/jir.12228) [x-mol.com]

  759.89 Birt-Hogg-Dube syndrome 759.89 Brachman-de Lange syndrome (Amsterdam dwarf, intellectual disabilities, and brachycephaly) 759.89 Brachymorphism and ectopia lentis 759.89 Bruck-de Lange disease or syndrome (Amsterdam dwarf, intellectual disabilities [icd9data.com]

  Other signs and symptoms may include intellectual disability and microcephaly (small head size). [rarediseases.info.nih.gov]

• Short Stature

  The father is affected and presents with a Pierre Robin sequence, short stature and typical costovertebral anomalies. CCMS is a rare and severe disorder. [ncbi.nlm.nih.gov]

  Very Small Stature, Not Skeletal Dysplasia. Moderate Short Stature, Facial, +/- Genital. Senile-Like Appearance. Early Overgrowth with Associated Defects. Unusual Brain And/Or Neuromuscular Findings with Associated Defects. [scinapse.io]

  stature, and intellectual disabilities) 759.89 Rud's (mental deficiency, epilepsy, and infantilism) 759.89 Russell (-Silver) (congenital hemihypertrophy and short stature) 759.89 Seckel's 759.89 sick Silver's (congenital hemihypertrophy and short stature [icd9data.com]

  Growth failure leading to short stature is sometimes due to a growth hormone deficiency. [findzebra.com]

  Examination of the propositas father showed short stature, very small thorax, and kyphoscoliosis. Severe micrognathia, cleft palate, and indistinct speech were also apparent. [docslide.com.br]

• Recurrent Infection

  Management includes intensive care for respiratory function, improving feeding difficulties, and recurrent infections. The majority of treatment is needed during infancy for survival to progress into adulthood. [todaysrdh.com]

• Respiratory Distress

  Cleft palate, feeding difficulties, respiratory distress, tracheostomy requirement, and scoliosis are common. Additional malformations such as horseshoe kidney, hypospadias, and septal heart defect may occur. [research-information.bris.ac.uk]

  Neonatal respiratory distress is common due to flail chest & airway abnormalities. [medicalchemy-syndromes.blogspot.com]

  Marked respiratory distress was present and the in fant was treated in the prone position in an in cubator with frequent pharyngeal suction, antibotics, and gavage, but died on the 14th day. [yumpu.com]

  Shortly after birth, he presented with signs of respiratory distress and central cyanosis. He was transferred to the neonatal intensive care unit. [go.galegroup.com]

  Most babies died due to respiratory distress. Although brain anomalies are uncommon in cerebro-costo-mandibular syndrome, hypoxia may cause neurodevelopmental disorders. [avesis.bezmialem.edu.tr]

• Nasal Voice

  […] speech Nasal voice 0001611 Patent ductus arteriosus 0001643 Polyhydramnios High levels of amniotic fluid 0001561 Posteriorly rotated ears Ears rotated toward back of head 0000358 Postnatal growth retardation Growth delay as children 0008897 Renal cyst [rarediseases.info.nih.gov]

• Failure to Thrive

  […] to thrive Glossoptosis Intellectual disabilities Fetal growth delays Kyphosis Short height Tracheomalacia Not common but also not rare symptoms include: Fifth finger clinodactyly Cerebral calcification Hydranencephaly Meningocele Microcephaly Polycystic [en.wikipedia.org]

  […] to thrive and conductive hearing loss (seen in about 10 % of cases).[3],[9] The developmental anomalies in our case with the estimated percentage of those described in literature[1] are given in [Table - 2]. [jpgmonline.com]

  […] to thrive and conductive hearing loss (seen in about 10 % of cases). 3,9 The developmental anomalies in our case with the estimated percentage of those described in literature 1 are given in Table 2. [bioline.org.br]

  Feeding problems and its outcome failure to thrive is an additional problem in these babies. Cleft palate may cause aspiration, nasogastric tube complications, and inadequate feeding (5). [go.galegroup.com]

  Feeding difficulties, (leading to failure to thrive), gastroesophageal reflux (GER), vomiting and constipation often appear in infancy but improve in childhood. Growth failure leading to short stature is sometimes due to a growth hormone deficiency. [findzebra.com]

• Receding Chin

  It’s considered hypoplasia of the mandible, causing a small, receding chin that is frequently associated with different syndromes. The development of the mandible is multifactorial. [todaysrdh.com]

• Hearing Impairment

  impairment Conductive deafness Conductive hearing loss [ more ] 0000405 Death in infancy Infantile death Lethal in infancy [ more ] 0001522 Feeding difficulties Feeding problems Poor feeding [ more ] 0011968 Glossoptosis Retraction of the tongue 0000162 [rarediseases.info.nih.gov]

• Narrow Thorax

  Key radiological findings are of a narrow thorax, multiple posterior rib gaps and abnormal costo-transverse articulation. A novel finding in 2 patients is bilateral accessory ossicles arising from the hyoid bone. [research-information.bris.ac.uk]

  The first boy had muscular hypotonia, severe micrognathia, glossoptosis, short palate, preauricular tag, paraumbilical fibroma, and a small and narrow thorax. [ncbi.nlm.nih.gov]

  The first boy had muscular hypotonia, severe micrognathia, glossoptosis, short; palate, preauricular tag, paraumbilical fibroma, and a small and narrow thorax. [rug.nl]

  Key radiological findings are of a narrow thorax, multiple posterior rib gaps, and abnormal costo-transverse articulation. Mortality is 35%-50% in the first year of life and death is due to respiratory failure. [genome.jp]

• Fracture

  The ribs characteristically have abnormal costovertebral articulations & posterior ossification gaps which resemble fractures. The posterior ossification gaps will ossify later in life. [medicalchemy-syndromes.blogspot.com]

  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. [symptoma.com]

  Thoracic X-ray may mimic multiple costal fractures at birth, especially when resuscitation is applied, as in our patient. Spontaneous rib fractures were also described in some cases of vaginal delivery [17]. [docplayer.net]

  Article) Autori Matic Aleksandra Velisavljev-Filipovic Gordana Lovrenski Jovan Gajdobranski Djordje Info SRPSKI ARHIV ZA CELOKUPNO LEKARSTVO, (2016), vol. 144 br. 7-8, str. 431-435 Ispravka ISI/Web of Science Članak Elečas Rang časopisa Naslov Scaphoid Fractures [kobson.nb.rs]

  Prenat Diagn (2005) 1.39 Fractures in premature infants. J Pediatr Orthop (1988) 1.38 Scalp changes after fetal monitoring. [pubrank.carbocation.com]

• Short Humerus

  humerus Short long bone of upper arm Short upper arms [ more ] 0005792 Thoracic hypoplasia Small chest Small thorax [ more ] 0005257 Showing of 56 | Last updated: 7/1/2019 The majority of cases of cerebro-costo-mandibular syndrome (CCMS) appear to occur [rarediseases.info.nih.gov]

• 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]

• Pierre Robin Syndrome

  Cerebro–costo–mandibular syndrome CCM syndrome rib gaps micrognathia Pierre Robin syndrome Persistent link APA Author BIBTEX Harvard Standard RIS Vancouver [research-information.bris.ac.uk]

  In Pierre-Robin syndrome, the life span is normal. [todaysrdh.com]

  Mentale Retardierung Key words: Pierre-Robin-syndrome - Rib defects - Cerebro-costo-mandibular syndrome - Mental retardation Literatur 1 Ibba R M. [doi.org]

  The cerebrocostomandibutar syndrome— a pierre robin-like syn- Google Scholar Nicholls SJ, Fletcher Ewl. Congenital rib defects with the pierre robin syndrome. Pediatr Radiol 1973; 1:246-7. [journals.sagepub.com]

  This rare dysmorphic disorder (only 51 cases have been reported to date) mainly associates defective costal development with features of the Pierre-Robin syndrome. The diagnosis is very often made at birth and the prognosis is very poor. [ncbi.nlm.nih.gov]

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].

Maintenance of airway patency is a key point in early treatment of infants with CCMS. [docplayer.net]

We present the clinical course and the early aggressive treatment of a newborn diagnosed as cerebro-costo-mandibular syndrome. The management of the patients with this syndrome is important over the morbidity and mortality. [avesis.bezmialem.edu.tr]

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]

There are two main types of clinical studies: Clinical trials determine if a new test or treatment for a disease is effective and safe by comparing groups receiving different tests/treatments. [rarediseases.info.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]

Case Reports Cerebro-costo-mandibular syndrome: prognosis and proposal for classification Hiroyuki Nagasawa et al. Congenit Anom (Kyoto). 2010 Sep. [pubmed.ncbi.nlm.nih.gov]

CCMS can be classified into three categories--lethal, severe, and mild--according to the severity of the symptoms and prognosis. [ncbi.nlm.nih.gov]

Skeletal - elbow hypoplasia, kyphosis, rib dysplasia, scoliosis, slow postnatal growth, vertebral fusion Neurological - microcephaly Psychiatric - mental retardation ( + ) Genitourinary - ectopic kidney Skin - excessive skin Differential Diagnosis: Prognosis [medicalchemy-syndromes.blogspot.com]

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. [symptoma.com]

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]

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]

“These studies,” says Professor Saint-Jeannet, will identify genes important for neural crest and craniofacial development, and will provide novel insights into the etiology and pathogenesis of Nager syndrome. [nyu.edu]

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]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]

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]

Management: Includes intensive care for improving neonatal respiratory function Prevention of feeding difficulties. Operative interventions - musculoskeletal, palatal or hearing problems. [medicalchemy-syndromes.blogspot.com]

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]

This oral condition displaces the tongue in a downward and backward position, which commonly obstructs the airway, throat, and pharynx, preventing sucking, swallowing, and feeding. [todaysrdh.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]

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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.