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Metaphyseal acroscyphodysplasia

General Information (adopted from Orphanet):

Synonyms, Signs:	CUPPED METAPHYSES AND CONE-SHAPED EPIPHYSES OF KNEES WITH BRACHYDACTYLY WEDGE-SHAPED EPIPHYSES OF KNEES Bellini syndrome Intellectual deficit - short stature - wedge shaped epiphyses of knees
Number of Symptoms	62
OrphanetNr:	1240
OMIM Id:	250215
ICD-10:	Q78.5
UMLs:	C1855243
MeSH:	C537350
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	4 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Neonatal [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Multiple metaphyseal dysplasia
-Rare bone disease
-Rare developmental defect during embryogenesis
-Rare genetic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0000463)	Anteverted nares		305 / 7739
2	(HPO:0000431)	Wide nasal bridge		290 / 7739
3	(HPO:0002007)	Frontal bossing	Frequent [Orphanet]	366 / 7739
4	(HPO:0000272)	Malar flattening		277 / 7739
5	(HPO:0000286)	Epicanthus	Frequent [Orphanet]	371 / 7739
6	(HPO:0001363)	Craniosynostosis		132 / 7739
7	(HPO:0000445)	Wide nose	Frequent [Orphanet]	190 / 7739
8	(HPO:0002684)	Thickened calvaria		32 / 7739
9	(HPO:0012368)	Flat face	Occasional [Orphanet]	106 / 7739
10	(HPO:0000506)	Telecanthus	Frequent [Orphanet]	156 / 7739
11	(HPO:0000316)	Hypertelorism	Frequent [Orphanet]	644 / 7739
12	(HPO:0011220)	Prominent forehead		137 / 7739
13	(HPO:0011800)	Midface retrusion		221 / 7739
14	(HPO:0000457)	Depressed nasal ridge	Frequent [Orphanet]	85 / 7739
15	(HPO:0001249)	Intellectual disability		1089 / 7739
16	(HPO:0001367)	Abnormal joint morphology	Frequent [Orphanet]	53 / 7739
17	(HPO:0002970)	Genu varum	Very frequent [Orphanet]	60 / 7739
18	(HPO:0001163)	Abnormality of the metacarpal bones	Very frequent [Orphanet]	149 / 7739
19	(HPO:0005792)	Short humerus		34 / 7739
20	(HPO:0006059)	Cone-shaped metacarpal epiphyses		3 / 7739
21	(HPO:0006205)	Irregular phalanges		1 / 7739
22	(HPO:0001385)	Hip dysplasia	Very frequent [Orphanet]	242 / 7739
23	(HPO:0010049)	Short metacarpal		99 / 7739
24	(HPO:0002650)	Scoliosis	Occasional [Orphanet]	705 / 7739
25	(HPO:0002823)	Abnormality of the femur	Very frequent [Orphanet]	61 / 7739
26	(HPO:0009827)	Amelia		12 / 7739
27	(HPO:0002673)	Coxa valga		57 / 7739
28	(HPO:0009803)	Short phalanx of finger		79 / 7739
29	(HPO:0009381)	Short finger		45 / 7739
30	(HPO:0002983)	Micromelia	Very frequent [Orphanet]	130 / 7739
31	(HPO:0004586)	Biconcave vertebral bodies		15 / 7739
32	(HPO:0000944)	Abnormality of the metaphyses	Very frequent [Orphanet]	141 / 7739
33	(HPO:0002982)	Tibial bowing		36 / 7739
34	(HPO:0003311)	Hypoplasia of the odontoid process		34 / 7739
35	(HPO:0005616)	Accelerated skeletal maturation	Very frequent [Orphanet]	46 / 7739
36	(HPO:0010579)	Cone-shaped epiphysis	Very frequent [Orphanet]	54 / 7739
37	(HPO:0003027)	Mesomelia		58 / 7739
38	(HPO:0003016)	Metaphyseal widening		41 / 7739
39	(HPO:0009829)	Phocomelia		20 / 7739
40	(HPO:0000926)	Platyspondyly		150 / 7739
41	(HPO:0006487)	Bowing of the long bones	Very frequent [Orphanet]	95 / 7739
42	(HPO:0005011)	Mesomelic arm shortening		13 / 7739
43	(HPO:0006494)	Aplasia/Hypoplasia involving bones of the feet	Very frequent [Orphanet]	69 / 7739
44	(HPO:0003021)	Metaphyseal cupping		16 / 7739
45	(HPO:0003275)	Narrow pelvis bone		8 / 7739
46	(HPO:0004279)	Short palm	Very frequent [Orphanet]	323 / 7739
47	(HPO:0000940)	Abnormal diaphysis morphology	Very frequent [Orphanet]	41 / 7739
48	(HPO:0001831)	Short toe		52 / 7739
49	(HPO:0010230)	Cone-shaped epiphyses of the phalanges of the hand		34 / 7739
50	(HPO:0003510)	Severe short stature		90 / 7739
51	(HPO:0004322)	Short stature	Very frequent [Orphanet]	1232 / 7739
52	(OMIM)	Brachydactyly, severe		4 / 7739
53	(OMIM)	Knee flexion		1 / 7739
54	(OMIM)	Progressive coxa valga		1 / 7739
55	(OMIM)	Short, irregular phalanges		1 / 7739
56	(OMIM)	Mild humeral shortening		1 / 7739
57	(HPO:0012758)	Neurodevelopmental delay	Frequent [Orphanet]	949 / 7739
58	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
59	(OMIM)	Distal femoral and proximal tibial cup-shaped epiphyses		1 / 7739
60	(OMIM)	Premature central epiphyso-metaphyseal fusion		1 / 7739
61	(OMIM)	Short, broad femurs		1 / 7739
62	(OMIM)	Elongated posterior clinoid processes		1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Based on 2 unrelated personal cases and a pair of sibs from the literature, Verloes et al. (1991) delineated a 'new' category of bone dysplasia with cup-shaped, large metaphyses. They suggested the name metaphyseal acroscyphodysplasia ('acro-' refers to ... Based on 2 unrelated personal cases and a pair of sibs from the literature, Verloes et al. (1991) delineated a 'new' category of bone dysplasia with cup-shaped, large metaphyses. They suggested the name metaphyseal acroscyphodysplasia ('acro-' refers to limb; 'scypho-' comes from scyphus, meaning cup). The main clinical features were severe growth retardation, micromelia predominating in the lower limbs, knee flexion, and severe brachydactyly. The radiologic appearance of the knees was considered specific: the lower femoral and upper tibial epiphyses were embedded in the metaphyses, which were severely cup-shaped. Premature central epiphyso-metaphyseal fusion and gross deformation, or even coalescence, of the femoral condyles, occurred. Femoral diaphyses were short and broad, and there was progressive coxa valga. Bowed and/or short stubby tibias with cone-shaped metaphyses, and varus deformity of the tibio-astragalian joint were other features. Slight deformation of the long bones occurred in the arms. The main signs of hand involvement were severe brachydactyly, brachymesophalangy, phalangeal and metacarpal cone-shaped epiphyses, and irregular, bent, and shortened diaphyses. One of the 2 unrelated cases had abnormal facies but was mentally normal; psychomotor retardation was present in 3 of 4 cases. The affected sibs, a boy and his sister, were reported by Bellini et al. (1984). One of these sibs had abnormal hair (see 609990). Verloes et al. (1991) considered autosomal recessive inheritance likely. Kozlowski et al. (1995) reported 2 sisters with distinctive radiographic features that combined cone-shaped epiphyses and cupped metaphyses of distal femora with spondyloepiphyseal dysplasia. The distinctive metaphyseal appearance at the knees was also described by Verloes et al. (1991) and characterized by association of the metaphyseal changes with very short hands and feet. Kozlowski et al. (1995) concluded that there is more than one bone dysplasia that presents with these distinctive radiographic knee appearances but that because of too few cases, no satisfactory classification of a group of disorders is possible. See also cupped metaphyses and cone-shaped epiphyses without alopecia or brachydactyly (609989).

Symptoms & Signs

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