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Cole-Carpenter syndrome

General Information (adopted from Orphanet):

Synonyms, Signs:	COLE-CARPENTER SYNDROME Bone fragility - craniosynostosis - proptosis - hydrocephalus
Number of Symptoms	39
OrphanetNr:	2050
OMIM Id:	112240
ICD-10:	Q78.0
UMLs:	C1862178
MeSH:	C535963
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	4 cases [Orphanet]
Inheritance:	Autosomal dominant Autosomal recessive Not applicable [Orphanet]
Age of onset:	Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Genetic multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
-Rare genetic disease
Multiple congenital anomalies/dysmorphic syndrome without intellectual deficit
-Rare developmental defect during embryogenesis
Primary bone dysplasia with decreased bone density
-Rare bone disease
-Rare developmental defect during embryogenesis
-Rare genetic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000262)	Turricephaly	Frequent [Orphanet]	38 / 7739
2	(HPO:0000586)	Shallow orbits		23 / 7739
3	(HPO:0000691)	Microdontia		104 / 7739
4	(HPO:0000494)	Downslanted palpebral fissures	Occasional [Orphanet]	328 / 7739
5	(HPO:0010299)	Abnormality of dentin	Frequent [Orphanet]	9 / 7739
6	(HPO:0000520)	Proptosis	Very frequent [Orphanet]	192 / 7739
7	(HPO:0004440)	Coronal craniosynostosis		38 / 7739
8	(HPO:0000684)	Delayed eruption of teeth	Very frequent [Orphanet]	117 / 7739
9	(HPO:0005472)	Orbital craniosynostosis		1 / 7739
10	(HPO:0011800)	Midface retrusion	Very frequent [Orphanet]	221 / 7739
11	(HPO:0002645)	Wormian bones	Frequent [Orphanet]	65 / 7739
12	(HPO:0000347)	Micrognathia		426 / 7739
13	(HPO:0002007)	Frontal bossing	Very frequent [Orphanet]	366 / 7739
14	(HPO:0000277)	Abnormality of the mandible	Very frequent [Orphanet]	394 / 7739
15	(HPO:0000592)	Blue sclerae	Very frequent [Orphanet]	85 / 7739
16	(HPO:0001382)	Joint hypermobility	Occasional [Orphanet]	231 / 7739
17	(HPO:0000944)	Abnormality of the metaphyses	Very frequent [Orphanet]	141 / 7739
18	(HPO:0002953)	Vertebral compression fractures		14 / 7739
19	(HPO:0002652)	Skeletal dysplasia	Very frequent [Orphanet]	113 / 7739
20	(HPO:0002757)	Recurrent fractures		47 / 7739
21	(HPO:0000938)	Osteopenia		138 / 7739
22	(HPO:0002808)	Kyphosis	Frequent [Orphanet]	289 / 7739
23	(HPO:0003312)	Abnormal form of the vertebral bodies	Very frequent [Orphanet]	172 / 7739
24	(HPO:0002650)	Scoliosis	Frequent [Orphanet]	705 / 7739
25	(HPO:0006487)	Bowing of the long bones	Very frequent [Orphanet]	95 / 7739
26	(HPO:0000772)	Abnormality of the ribs	Very frequent [Orphanet]	146 / 7739
27	(HPO:0002659)	Increased susceptibility to fractures	Frequent [Orphanet]	110 / 7739
28	(HPO:0004349)	Reduced bone mineral density	Very frequent [Orphanet]	165 / 7739
29	(HPO:0004322)	Short stature	Very frequent [Orphanet]	1232 / 7739
30	(HPO:0001511)	Intrauterine growth retardation	Frequent [Orphanet]	358 / 7739
31	(HPO:0001620)	High pitched voice		32 / 7739
32	(HPO:0001608)	Abnormality of the voice	Very frequent [Orphanet]	126 / 7739
33	(HPO:0001252)	Muscular hypotonia	Frequent [Orphanet]	990 / 7739
34	(HPO:0012758)	Neurodevelopmental delay	Occasional [Orphanet]	949 / 7739
35	(MedDRA:10070918)	Bone deformity		2 / 7739
36	(HPO:0001334)	Communicating hydrocephalus	Frequent [Orphanet]	32 / 7739
37	(HPO:0000006)	Autosomal dominant inheritance		2518 / 7739
38	(HPO:0000238)	Hydrocephalus		278 / 7739
39	(OMIM)	Normal intellectual development		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Cole and Carpenter (1987) described a seemingly new osteogenesis imperfecta-like disorder in 2 unrelated infants. Both had bone deformities and multiple fractures reminiscent of OI but also had ocular proptosis with orbital craniosynostosis, hydrocephalus, and distinctive facial features. ... Cole and Carpenter (1987) described a seemingly new osteogenesis imperfecta-like disorder in 2 unrelated infants. Both had bone deformities and multiple fractures reminiscent of OI but also had ocular proptosis with orbital craniosynostosis, hydrocephalus, and distinctive facial features. Both infants were normal at birth; before the first birthday, however, recurrent diaphyseal fractures of the weight-bearing bones had occurred. Despite the craniosynostosis and hydrocephalus, intellectual development was unimpaired. The parents were unrelated in each case; their ages were not stated. In the first case the mother was noted to have somewhat shallow orbits and her father and grandmother had similar features; a paternal aunt had been examined for hyperthyroidism because of clinically evident proptosis. In this patient, frontal craniectomy was performed at age 9 months to relieve compression of the ocular globes because of an alarming progression of proptosis and frontal bossing. Progressive communicating hydrocephalus was noted by computer tomography at 12 months of age and a lumboperitoneal shunt was established to be replaced later by a ventriculoperitoneal shunt. MacDermot et al. (1995) reported the case of a male infant thought to represent either the more severe end of the spectrum of type IV osteogenesis imperfecta (166220) or the mild end of the spectrum of Cole-Carpenter syndrome. Severe hydrops fetalis developed between 19 and 28 weeks of gestation. After delivery at 32 weeks, he was treated by hemofiltration, prolonged ventilation, and intravenous feeding. He had hypertelorism, orbital hypoplasia without proptosis, brachydactyly, frontal and temporal bossing of the skull, central hypotonia, communicating hydrocephalus, and severe delay in psychomotor development. Signs of connective tissue disorder included osteopenia, pathologic fracture, yellow/gray discolored teeth, blue sclerae, and easy bruising. Amor et al. (2000) reported a girl with clinical features similar to the 2 cases presented by Cole and Carpenter (1987). This patient had a severe progressive type of osteogenesis imperfecta, multisutural craniosynostosis, growth failure, and craniofacial findings, including ocular proptosis, marked frontal bossing, midface hypoplasia, and micrognathia. Analysis of type I collagen was normal.

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