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Craniometaphyseal dysplasia, autosomal dominant(CMDD)

MedGen UID:
338945
Concept ID:
C1852502
Disease or Syndrome
Synonyms: CMDD; Craniometaphyseal dysplasia Jackson type
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Sources: HPO, OMIM
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
 
Gene (location): ANKH (5p15.2)
 
OMIM®: 123000

Disease characteristics

Autosomal dominant craniometaphyseal dysplasia (designated AD-CMD in this review) is characterized by progressive diffuse hyperostosis of cranial bones evident clinically as wide nasal bridge, paranasal bossing, widely spaced eyes with an increase in bizygomatic width, and prominent mandible. Development of dentition may be delayed and teeth may fail to erupt as a result of hyperostosis and sclerosis of alveolar bone. Progressive thickening of craniofacial bones continues throughout life, often resulting in narrowing of the cranial foramina, including the foramen magnum. If untreated, compression of cranial nerves can lead to disabling conditions such as facial palsy, blindness, or deafness (conductive and/or sensorineural hearing loss). In individuals with typical uncomplicated AD-CMD life expectancy is normal; in those with severe AD-CMD life expectancy can be reduced as a result of compression of the foramen magnum. [from GeneReviews]
Authors:
Ernst Reichenberger  |  I-Ping Chen   view full author information

Additional descriptions

From OMIM
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, which may finally result in hearing loss and facial palsy (summary by Nurnberg et al., 1997). The delineation of separate autosomal dominant and autosomal recessive (CMDR; 218400) 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, while the recessive form is rare, severe, and possibly heterogeneous.  http://www.omim.org/entry/123000
From MedlinePlus Genetics
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.\n\nBone 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.\n\nThe 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.\n\nThere 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.  https://medlineplus.gov/genetics/condition/craniometaphyseal-dysplasia

Clinical features

From HPO
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Erlenmeyer flask deformity of the femurs
MedGen UID:
383796
Concept ID:
C1855895
Finding
Flaring of distal femur.
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.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Mixed conductive AND sensorineural hearing loss
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.
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.
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.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
Abnormal widening of the metaphyseal regions of long bones.
Sclerosis of skull base
MedGen UID:
377095
Concept ID:
C1851714
Finding
Increased bone density of the skull base without significant changes in bony contour.
Calvarial osteosclerosis
MedGen UID:
340927
Concept ID:
C1855657
Finding
An increase in bone density affecting the calvaria (roof of the skull).
Erlenmeyer flask deformity of the femurs
MedGen UID:
383796
Concept ID:
C1855895
Finding
Flaring of distal femur.
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.
Macrocephalus
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.
Abnormality of pelvic girdle bone morphology
MedGen UID:
866545
Concept ID:
C4020847
Anatomical Abnormality
An abnormality of the bony pelvic girdle, which is a ring of bones connecting the vertebral column to the femurs.
Abnormality of the vertebral column
MedGen UID:
892426
Concept ID:
C4021789
Anatomical Abnormality
Any abnormality of the vertebral column.
Abnormality of the nasopharynx
MedGen UID:
871265
Concept ID:
C4025750
Anatomical Abnormality
A structural anomaly of the nasopharynx.
Nasal obstruction
MedGen UID:
10266
Concept ID:
C0027429
Finding
Blockage of the nasal passages.
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.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Sclerosis of skull base
MedGen UID:
377095
Concept ID:
C1851714
Finding
Increased bone density of the skull base without significant changes in bony contour.
Misalignment of teeth
MedGen UID:
377692
Concept ID:
C1852504
Finding
Abnormal alignment, positioning, or spacing of the teeth, i.e., misaligned teeth.
Calvarial osteosclerosis
MedGen UID:
340927
Concept ID:
C1855657
Finding
An increase in bone density affecting the calvaria (roof of the skull).
Bony paranasal bossing
MedGen UID:
341786
Concept ID:
C1857499
Finding
Macrocephalus
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.
Abnormality of the nasopharynx
MedGen UID:
871265
Concept ID:
C4025750
Anatomical Abnormality
A structural anomaly of the nasopharynx.
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 (145410), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Recent clinical studies

Etiology

Prontera P, Rogaia D, Sobacchi C, Tavares VL, Mazzotta G, Passos-Bueno MR, Donti E
Am J Med Genet A 2011 May;155A(5):1106-8. Epub 2011 Apr 4 doi: 10.1002/ajmg.a.33826. PMID: 21465646

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