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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, Orphanet
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
Autosomal dominant inheritance (HPO, OMIM, Orphanet)
 
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, that 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 GHR
Craniometaphyseal dysplasia is a rare condition characterized by progressive thickening of bones in the skull (cranium) and abnormalities at the ends of long bones in the limbs (metaphyseal dysplasia). Except in the most severe cases, the lifespan of people with craniometaphyseal dysplasia is normal.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. Excessive new bone formation (hyperostosis) in the jaw can delay teething (dentition) or result in absent (non-erupting) teeth. Infants with this condition may have breathing or feeding problems caused by narrow nasal passages. In severe cases, abnormal bone growth can compress the nerves that emerge from the brain and extend 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.The x-rays of individuals with craniometaphyseal dysplasia show unusually shaped long bones, particularly the large bones in the legs. The ends of these bones (metaphyses) are wider and appear less dense in people with this condition.There are two types of craniometaphyseal dysplasia, which are distinguished by their pattern of inheritance. They are known as the autosomal dominant and autosomal recessive types. Autosomal recessive craniometaphyseal dysplasia is typically more severe than the autosomal dominant form.  https://ghr.nlm.nih.gov/condition/craniometaphyseal-dysplasia

Clinical features

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).
Metaphyseal widening
MedGen UID:
341364
Concept ID:
C1849039
Finding
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
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
Height greater than two standard deviations below the mean of the appropriate reference population for the age and sex of the individual.
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.
Facial paralysis
MedGen UID:
98103
Concept ID:
C0427055
Sign or Symptom
Complete loss of ability to move facial muscles innervated by the facial nerve (i.e., the seventh cranial nerve).
Facial paralysis
MedGen UID:
98103
Concept ID:
C0427055
Sign or Symptom
Complete loss of ability to move facial muscles innervated by the facial nerve (i.e., the seventh cranial nerve).
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
A radiologic finding characterized by an increased width of the metaphyseal regions. It is seen in rickets.
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.
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).
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.
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).
Nasal obstruction
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.
Facial paralysis
MedGen UID:
98103
Concept ID:
C0427055
Sign or Symptom
Complete loss of ability to move facial muscles innervated by the facial nerve (i.e., the seventh cranial nerve).
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
Macrocephaly
MedGen UID:
745757
Concept ID:
C2243051
Finding
Macrocephaly refers to an abnormally enlarged head inclusive of the scalp, cranial bones, and intracranial contents. Macrocephaly may be due to megalencephaly (true enlargement of the brain parenchyma), and the 2 terms are often used interchangeably in the genetic literature (reviews by Olney, 2007 and Williams et al., 2008). Autosomal recessive macrocephaly/megalencephaly syndrome is characterized by an enlarged cranium apparent at birth or in early childhood. Affected individuals have intellectual disability and may have dysmorphic facial features resulting from the macrocephaly (summary by Alfaiz et al., 2014).
Abnormality of the nasopharynx
MedGen UID:
425069
Concept ID:
CN001583
Finding

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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