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Craniometaphyseal dysplasia, autosomal recessive(CMDR)

MedGen UID:
419753
Concept ID:
C2931244
Disease or Syndrome
Synonym: CMDR
 
Gene (location): GJA1 (6q22.31)
 
Monarch Initiative: MONDO:0009035
OMIM®: 218400

Definition

Craniometaphyseal dysplasia is an osteochondrodysplasia characterized by hyperostosis and sclerosis of the craniofacial bones associated with abnormal modeling of the metaphyses. Sclerosis of the skull may lead to asymmetry of the mandible, as well as to cranial nerve compression, that may finally result in hearing loss and facial palsy (summary by Nurnberg et al., 1997). The delineation of separate autosomal dominant (CMDD; 123000) and autosomal recessive forms of CMD by Gorlin et al. (1969) was confirmed by reports that made it evident that the dominant form is relatively mild and comparatively common, whereas the recessive form is rare, severe, and possibly heterogeneous. [from OMIM]

Additional description

From MedlinePlus Genetics
There are two types of craniometaphyseal dysplasia, which are distinguished by their pattern of inheritance and genetic cause. They are known as the autosomal dominant and autosomal recessive types.

The x-rays of individuals with craniometaphyseal dysplasia show unusually shaped long bones, particularly long bones in the legs. The ends of these bones are wider and appear less dense than usual in people with this condition.

Bone overgrowth in the head causes many of the signs and symptoms of craniometaphyseal dysplasia. Affected individuals typically have distinctive facial features such as a wide nasal bridge, a prominent forehead, wide-set eyes (hypertelorism), and a prominent jaw. Excess bone formation in the jaw can delay teething (dentition) or result in absent (non-erupting) teeth. Infants with craniometaphyseal dysplasia may have breathing or feeding problems caused by narrow nasal passages. In severe cases, abnormal bone growth can pinch (compress) the nerves that extend from the brain to various areas of the head and neck (cranial nerves). Compression of the cranial nerves can lead to paralyzed facial muscles (facial nerve palsy), blindness, or deafness.

Craniometaphyseal dysplasia is a rare condition characterized by thickening (overgrowth) of bones in the skull (cranium) and abnormalities in a region at the end of long bones known as the metaphysis. The abnormal bone growth continues throughout life. Except in the most severe cases, the lifespan of people with craniometaphyseal dysplasia is normal.  https://medlineplus.gov/genetics/condition/craniometaphyseal-dysplasia

Clinical features

From HPO
Club-shaped distal femur
MedGen UID:
346601
Concept ID:
C1857505
Finding
An abnormal conformation of the femur that becomes gradually enlarged towards the distal end. This feature affects the distal femoral metaphysis and epiphysis.
Patchy sclerosis of finger phalanx
MedGen UID:
341789
Concept ID:
C1857508
Finding
Uneven (irregular) increase in bone density of one or more of the phalanges of the hand.
Mixed hearing impairment
MedGen UID:
102336
Concept ID:
C0155552
Disease or Syndrome
A type of hearing loss resulting from a combination of conductive hearing impairment and sensorineural hearing impairment.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Facial palsy
MedGen UID:
87660
Concept ID:
C0376175
Disease or Syndrome
Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form.
Flared metaphysis
MedGen UID:
337976
Concept ID:
C1850135
Finding
The presence of a splayed (i.e.,flared) metaphyseal segment of one or more long bones.
Facial hyperostosis
MedGen UID:
347471
Concept ID:
C1857501
Finding
Excessive growth (overgrowth) of the facial bones, that is of the facial skeleton.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Occipitofrontal (head) circumference greater than 97th centile compared to appropriate, age matched, sex-matched normal standards. Alternatively, a apparently increased size of the cranium.
Abnormal thorax morphology
MedGen UID:
867424
Concept ID:
C4021797
Anatomical Abnormality
Any abnormality of the thorax (the region of the body formed by the sternum, the thoracic vertebrae and the ribs).
Metaphyseal dysplasia
MedGen UID:
1677924
Concept ID:
C5194606
Disease or Syndrome
The presence of dysplastic regions in metaphyseal regions.
Abnormal nasopharynx morphology
MedGen UID:
871265
Concept ID:
C4025750
Anatomical Abnormality
A structural anomaly of the nasopharynx.
Nasal congestion
MedGen UID:
6523
Concept ID:
C0027424
Sign or Symptom
Reduced ability to pass air through the nasal cavity often leading to mouth breathing.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Telecanthus
MedGen UID:
140836
Concept ID:
C0423113
Finding
Distance between the inner canthi more than two standard deviations above the mean (objective); or, apparently increased distance between the inner canthi.
Depressed nasal ridge
MedGen UID:
334631
Concept ID:
C1842876
Finding
Lack of prominence of the nose resulting from a posteriorly-placed nasal ridge.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.
Wide nasal bridge
MedGen UID:
341441
Concept ID:
C1849367
Finding
Increased breadth of the nasal bridge (and with it, the nasal root).
Delayed eruption of permanent teeth
MedGen UID:
340353
Concept ID:
C1849540
Finding
Delayed tooth eruption affecting the secondary dentition.
Bony paranasal bossing
MedGen UID:
341786
Concept ID:
C1857499
Finding
Broad alveolar ridges
MedGen UID:
347470
Concept ID:
C1857500
Finding
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).
Optic atrophy
MedGen UID:
18180
Concept ID:
C0029124
Disease or Syndrome
Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy.