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Spondylometaphyseal dysplasia - cone-rod dystrophy

General Information (adopted from Orphanet):

Synonyms, Signs:	SMD-CRD SMDCRD
Number of Symptoms	48
OrphanetNr:	85167
OMIM Id:	608940
ICD-10:	H35.5 Q77.8
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	8 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	No data available [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

Spondylometaphyseal dysplasia
-Rare bone disease
-Rare developmental defect during embryogenesis
-Rare genetic disease

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	Pubmed	Source	DB Freq
1	(HPO:0000483)	Astigmatism	Frequent [Orphanet]			67 / 7739
2	(HPO:0008002)	Abnormality of macular pigmentation				20 / 7739
3	(HPO:0000510)	Rod-cone dystrophy	Very frequent [Orphanet]			266 / 7739
4	(HPO:0000548)	Cone/cone-rod dystrophy				47 / 7739
5	(HPO:0000639)	Nystagmus	Frequent [Orphanet]			555 / 7739
6	(HPO:0000540)	Hypermetropia	Frequent [Orphanet]			99 / 7739
7	(HPO:0000545)	Myopia	Frequent [Orphanet]			286 / 7739
8	(HPO:0000642)	Red-green dyschromatopsia	Frequent [Orphanet]			25 / 7739
9	(HPO:0000613)	Photophobia	Frequent [Orphanet]			158 / 7739
10	(HPO:0000572)	Visual loss	Frequent [Orphanet]			272 / 7739
11	(HPO:0000529)	Progressive visual loss				54 / 7739
12	(HPO:0004322)	Short stature	Very frequent [Orphanet]			1232 / 7739
13	(HPO:0008905)	Rhizomelia	Very frequent [Orphanet]			85 / 7739
14	(HPO:0000403)	Recurrent otitis media				61 / 7739
15	(HPO:0006487)	Bowing of the long bones	Very frequent [Orphanet]			95 / 7739
16	(HPO:0002980)	Femoral bowing				36 / 7739
17	(HPO:0002982)	Tibial bowing				36 / 7739
18	(HPO:0009381)	Short finger				45 / 7739
19	(HPO:0001156)	Brachydactyly syndrome				180 / 7739
20	(HPO:0002812)	Coxa vara				58 / 7739
21	(HPO:0008821)	Hypoplastic inferior ilia				1 / 7739
22	(HPO:0001385)	Hip dysplasia	Very frequent [Orphanet]			242 / 7739
23	(HPO:0000944)	Abnormality of the metaphyses	Very frequent [Orphanet]			141 / 7739
24	(HPO:0003021)	Metaphyseal cupping				16 / 7739
25	(HPO:0003025)	Metaphyseal irregularity				42 / 7739
26	(HPO:0003016)	Metaphyseal widening				41 / 7739
27	(HPO:0010049)	Short metacarpal				99 / 7739
28	(HPO:0004279)	Short palm	Occasional [Orphanet]			323 / 7739
29	(HPO:0003375)	Narrow greater sacrosciatic notches				13 / 7739
30	(HPO:0000772)	Abnormality of the ribs	Frequent [Orphanet]			146 / 7739
31	(HPO:0000887)	Cupped ribs				9 / 7739
32	(HPO:0003300)	Ovoid vertebral bodies				21 / 7739
33	(HPO:0000926)	Platyspondyly	Very frequent [Orphanet]			150 / 7739
34	(HPO:0004565)	Severe platyspondyly				13 / 7739
35	(HPO:0003307)	Hyperlordosis	Frequent [Orphanet]			122 / 7739
36	(HPO:0002650)	Scoliosis	Frequent [Orphanet]			705 / 7739
37	(HPO:0001387)	Joint stiffness	Occasional [Orphanet]	24387990	IBIS	322 / 7739
38	(HPO:0002657)	Spondylometaphyseal dysplasia				12 / 7739
39	(HPO:0000689)	Dental malocclusion				114 / 7739
40	(HPO:0008897)	Postnatal growth retardation				113 / 7739
41	(HPO:0000007)	Autosomal recessive inheritance				2538 / 7739
42	(MedDRA:10072883)	Brachydactyly				153 / 7739
43	(OMIM)	Flat acetabuli				1 / 7739
44	(OMIM)	Mild platyspondyly				14 / 7739
45	(OMIM)	Normal facies				9 / 7739
46	(OMIM)	Rhizomelic shortening				12 / 7739
47	(OMIM)	Thick proximal and middle phalanges				1 / 7739
48	(OMIM)	Vision impairment, progressive				2 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Walters et al. (2004) described 8 cases (4 female and 4 male) of an apparently unique form of spondylometaphyseal dysplasia (SMD) characterized by concomitant cone-rod dystrophy (CRD). Three of the 8 cases were sibs. One of the 8 ... Walters et al. (2004) described 8 cases (4 female and 4 male) of an apparently unique form of spondylometaphyseal dysplasia (SMD) characterized by concomitant cone-rod dystrophy (CRD). Three of the 8 cases were sibs. One of the 8 cases was the product of a first-cousin union. Walters et al. (2004) stated that 3 sets of clinical features, in addition to autosomal recessive inheritance, allowed for definition of SMD-CRD as distinct from previously described conditions: (1) postnatal growth deficiency, profound short stature, rhizomelic foreshortening of the limbs, and early bowing of the long bones of the legs; (2) platyspondyly and characteristic vertebral body shape, progressive metaphyseal irregularity and cupping, and shortening of all the tubular bones; and (3) early onset and progressive visual impairment (perhaps with stabilization in adolescence), clinical evidence for pigmentary maculopathy, and electrophysiologic demonstration of cone-rod dystrophy. Distinguishing SMD-CRD from other forms of SMD were the absence of corner fractures, vertebral bodies that were ovoid and distinctively abnormal, severity that was far less than in the Sedaghatian form of SMD (250220), and absence of enchondromatous changes. Walters et al. (2004) suggested that SMD-CRD is probably not rare. Sousa et al. (2008) reported 3 patients with SMD-CRD: a 16-year-old boy, born of healthy, unrelated parents, and 4-year-old female African American twins, born of a consanguineous union. They found that the boy had low alpha-neuraminidase activity levels in fibroblasts (residual activity of about 5%), but normal levels in leukocytes. They suggested that SMD-CRD may be a metabolic disorder in which lowered neuraminidase levels are a secondary phenomenon. Kitoh et al. (2011) described a 16-year-old Japanese boy with a skeletal phenotype identical to that of previously reported patients with SMD-CRD. Profound short stature with rhizomelic shortening of the limbs was observed early in infancy. There was increased bowing deformity of the long bones of the legs with progressive metaphyseal flaring, cupping, fragmentation, and sclerosis. Platyspondyly was associated with ovoid-shaped vertebral bodies, and anterior wedging of the vertebrae was found in adolescence. In addition, he had prominent joints with limited mobility in knees and elbows and mild thoracic scoliosis. Vision impairment was first recognized at 11 years of age; funduscopy revealed bilateral macular chorioretinal atrophic lesions of variable sizes. Optical coherence tomography demonstrated bilateral retinal thinning, and full-field electroretinography (ERG) showed marked reduction of the cone response, although the rod response was relatively preserved, consistent with a mild form of cone dystrophy. Kitoh et al. (2011) noted that the ophthalmologic findings in this patient were relatively milder than those in previously reported patients.

Symptoms & Signs

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