Paula and Bobby
Parents of Lillie
Cerebrocostomandibular syndrome (CCMS)
What is Cerebrocostomandibular syndrome (CCMS)?
This rare disease is a very rare genetic syndrome. There are currently 80 cases recorded, to date.
The syndrome mainly affects the development of the ribs and jaw of affected individuals.
However it also presents with a wide range of symptoms that affect many different parts and systems of the body.
This syndrome is also known as:
CCMS Rib Gap Defects With Micrognathia Rib-gap syndrome
What gene changes cause Cerebrocostomandibular syndrome (CCMS)?
Mutations in the SNRPB gene have been identified as one of the causes of the syndrome. However continued research may uncover other genes that may cause the condition as some individuals with the symptoms of the syndrome do not show mutations in the SNRPB gene.
So far the majority of cases of the syndrome have been the result of de novo mutations of the gene.
In some cases, a genetic syndrome may be the result of a de-novo mutation and the first case in a family. In this case, this is a new gene mutation which occurs during the reproductive process.
What are the main symptoms of Cerebrocostomandibular syndrome (CCMS)?
The main symptoms of the syndrome affect the ribs and jaw. Individuals often have ribs missing, or spaces between the ribs. They also have a narrow rib cage. Individuals are also born with a much smaller jaw than the average (micrognathia).
50% of individuals will suffer from scoliosis (sideways curvature of the spine).
The Pierre Robin sequence of symptoms is associated with this syndrome. This includes a cleft palate, a small jaw and a tongue that is positioned further back in the mouth than it should be.
Infants with the syndrome usually experience breathing and feeding difficulties as newborns. Surgery is often required in the first year of life to correct these issues.
An estimated 67% of individuals affected by the syndrome will suffer hearing loss.
50% of individuals will be affected by developmental delay. This may include intellectual disability as well.
Physical features associated with the syndrome include club feet, a small head, low weight and failure to thrive, and a short stature.
Individuals with the syndrome may also suffer from health conditions affecting the stomach, heart, kidneys and urinary tract.
Possible clinical traits/features:
Atresia of the external auditory canal, Malar flattening, Clinodactyly of the 5th finger, Congenital hip dislocation, Cleft soft palate, Bell-shaped thorax, Ectopic kidney, Conductive hearing impairment, Epicanthus, Elbow flexion contracture, Nasal speech, Kyphosis, Short stature, High palate, Hydranencephaly, Short humerus, Glossoptosis, Cognitive impairment, Postnatal growth retardation, Low-set ears, Long philtrum, 11 pairs of ribs, Neonatal respiratory distress, Intellectual disability, Intrauterine growth retardation, Multicystic kidney dysplasia, Micrognathia, Myelomeningocele, Microcephaly, Short hard palate, Ventricular septal defect, Scoliosis, Tracheomalacia, Thoracic hypoplasia, Calcaneal epiphyseal stippling, Autosomal dominant inheritance, Posteriorly rotated ears, Porencephalic cyst, Autosomal recessive inheritance, Webbed neck, Abnormality of the dentition, Cerebral calcification, Polyhydramnios, Anomalous rib insertion to vertebrae
How does someone get tested for Cerebrocostomandibular syndrome (CCMS)?
The initial testing for Cerebrocostomandibular syndrome (CCMS) can begin with facial analysis screening, through the FDNA Telehealth telegenetics platform, which can identify the key markers of the syndrome and outline the need for further testing. A consultation with a genetic counselor and then a geneticist will follow.
Based on this clinical consultation with a geneticist, the different options for genetic testing will be shared and consent will be sought for further testing.
Medical information on Cerebrocostomandibular syndrome (CCMS)
The cardinal features are the presence at birth of a severe Pierre Robin sequence (a very small jaw, a U-shaped cleft palate and glossoptosis), posterior rib gaps, and mental retardation in about half of those who survive. Early death occurs in 40% of cases, due mainly to respiratory difficulties. Microcephaly occurs in only 20% of cases, and the small number of post mortems so far carried out have shown cerebral heterotopia and focal gliosis, but this is not constant. Survivors are short, have epicanthic folds, and the rib gaps might heal partially and give rise to pseudoarthroses. Ibba et al., (1997) reported a case diagnosed by ultrasound at prenatal diagnosis. There was increased nuchal transluceny at 11 weeks and micrognathia was noted at 12 weeks with failure to identify the ribs at 18 weeks. Plotz et al., (1996) provide a good review. Hannam et al., (2000) provide a good review of rib abnormalities in the neonate.
Affected sibs with apparently normal parents have been reported (Hennekam et al., (1985); Drossou-Agakidou et al., 1991). However, there is also a dominantly inherited form of cerebro-costo-mandibular syndrome which has speech delay, but a normal head circumference and a normal IQ (Leroy et al., 1981; Merlob et al., 1987; Flodmark and Wattsgard., 2001). In general the two types cannot be distinguished clinically. A further father and daughter pair was reported by Morin et al., (2001). The daughter was picked up by ultrasound examination at 16 weeks of gestation. In isolated cases the parents must be X-rayed.
Hennekam and Goldschmeding (1998) reported a female infant born at 34 weeks with a very severe form of the condition. There was total absence of ossification of the ribs, extreme micrognathia and also absence of the external auditory meati and inner ears. The authors suggest that the Myf5 and MyoD genes are candidates for this condition. Goosecoid is also a candidate.
Van den Ende et al., (1998) reported seven patients with the condition. One 12 year old boy (previously reported by Meinecke et al., 1987 and Schrander-Stumpel et al., 1996) attended a normal school but had bilateral hearing loss. A 36 year old female had normal psychodevelopment although her 14 month old daughter was affected and suffered severe perinatal asphyxia resulting in encephalopathy with cortical atrophy and convulsions. A 14 year old girl had normal psychomotor development. Previously unreported features including absence of auditory canal and subluxation of the radial head in one case and choanal atresia in another. Kirk and Ades (1998) reported a case with a hypoplastic left heart. James and Aftimos, (2003) reported an affected father and son. They reviewed literature and concluded that autosomal dominant and autosomal recessive cases cannot be distinguished on clinical features.
Mutations in the gene SNRPB have now been found to be causitive (Lynch et al., 2014, Bacrot et al., 2015)
Tooley et al. (2016) described 12 sporadic and 4 familial patients with cerebrocostomandibular syndrome. yndrome. SNRPB mutations were identified in 12 out of 14 patients for whom DNA was available (4 of them previously reported). The most typical features were severe micrognathia and reduced numbers of ribs with gaps. Other common features included cleft palate, respiratory distress and scoliosis. Horseshoe kidney, hypospadias, and septal heart defect were additional malformations. Microcephaly and significant developmental delay were present in a minority of patients. Key radiological findings were narrow thorax, multiple posterior rib gaps and abnormal costotransverse articulation. The authors also described a previously unknown feature - bilateral accessory ossicles arising from the hyoid bone.
* This information is courtesy of the L M D.
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