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Spondylometaphyseal dysplasia, Sedaghatian type

General Information (adopted from Orphanet):

Synonyms, Signs:	METAPHYSEAL CHONDRODYSPLASIA, CONGENITAL LETHAL SEDAGHATIAN CHONDRODYSPLASIA
Number of Symptoms	67
OrphanetNr:	93317
OMIM Id:	250220
ICD-10:	Q77.8
UMLs:	C1855229
MeSH:	C535798
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence:	9 cases [Orphanet]
Inheritance:	Autosomal recessive [Orphanet]
Age of onset:	Neonatal Infancy [Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases:

AARSKOG SYNDROME, AUTOSOMAL DOMINANT
-AARSKOG SYNDROME, AUTOSOMAL DOMINANT
Spondylodysplastic dysplasia
-Rare bone disease
-Rare developmental defect during embryogenesis
-Rare genetic disease

Comment:

Spondylometaphyseal dysplasia, Sedaghatian-type (SSMD) is characterised by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, cardiac conduction defects, and central nervous system abnormalities (PMID:24706940).

Symptom Information: Sort by abundance

	Symptom Information	Symptom	Abundance	DB Freq
1	(HPO:0004322)	Short stature	Very frequent [Orphanet]	1232 / 7739
2	(HPO:0003498)	Disproportionate short stature		28 / 7739
3	(HPO:0008905)	Rhizomelia	Very frequent [Orphanet]	85 / 7739
4	(HPO:0001631)	Atria septal defect		274 / 7739
5	(HPO:0011025)	Abnormality of cardiovascular system physiology	Very frequent [Orphanet]	41 / 7739
6	(HPO:0011675)	Arrhythmia	Very frequent [Orphanet]	226 / 7739
7	(HPO:0001695)	Cardiac arrest	Very frequent [Orphanet]	87 / 7739
8	(HPO:0001252)	Muscular hypotonia		990 / 7739
9	(HPO:0008947)	Infantile muscular hypotonia		482 / 7739
10	(HPO:0010547)	Muscle flaccidity		466 / 7739
11	(HPO:0001324)	Muscle weakness		859 / 7739
12	(HPO:0006059)	Cone-shaped metacarpal epiphyses		3 / 7739
13	(HPO:0010230)	Cone-shaped epiphyses of the phalanges of the hand		34 / 7739
14	(HPO:0009803)	Short phalanx of finger		79 / 7739
15	(HPO:0009381)	Short finger		45 / 7739
16	(HPO:0001831)	Short toe		52 / 7739
17	(HPO:0001156)	Brachydactyly syndrome		180 / 7739
18	(HPO:0001762)	Talipes equinovarus		309 / 7739
19	(HPO:0003085)	Long fibula		5 / 7739
20	(HPO:0003180)	Flat acetabular roof		25 / 7739
21	(HPO:0011867)	Abnormality of the wing of the ilium	Very frequent [Orphanet]	123 / 7739
22	(HPO:0002869)	Flared iliac wings		20 / 7739
23	(HPO:0008786)	Iliac crest serration		4 / 7739
24	(HPO:0008798)	Widened sacrosciatic notch		1 / 7739
25	(HPO:0004688)	Irregular tarsal bones		1 / 7739
26	(HPO:0000944)	Abnormality of the metaphyses	Very frequent [Orphanet]	141 / 7739
27	(HPO:0003021)	Metaphyseal cupping		16 / 7739
28	(HPO:0003025)	Metaphyseal irregularity		42 / 7739
29	(HPO:0001163)	Abnormality of the metacarpal bones	Very frequent [Orphanet]	149 / 7739
30	(HPO:0010049)	Short metacarpal		99 / 7739
31	(HPO:0004279)	Short palm	Very frequent [Orphanet]	323 / 7739
32	(HPO:0003375)	Narrow greater sacrosciatic notches		13 / 7739
33	(HPO:0004491)	Large posterior fontanelle		3 / 7739
34	(HPO:0000262)	Turricephaly	Frequent [Orphanet]	38 / 7739
35	(HPO:0000772)	Abnormality of the ribs	Very frequent [Orphanet]	146 / 7739
36	(HPO:0000887)	Cupped ribs		9 / 7739
37	(HPO:0000921)	Missing ribs	Occasional [Orphanet]	62 / 7739
38	(HPO:0000878)	11 pairs of ribs		19 / 7739
39	(HPO:0000912)	Sprengel anomaly	Very frequent [Orphanet]	51 / 7739
40	(HPO:0000774)	Narrow chest	Frequent [Orphanet]	167 / 7739
41	(HPO:0000773)	Short ribs		70 / 7739
42	(HPO:0000926)	Platyspondyly	Very frequent [Orphanet]	150 / 7739
43	(HPO:0000470)	Short neck		345 / 7739
44	(HPO:0007370)	Aplasia/Hypoplasia of the corpus callosum	Occasional [Orphanet]	180 / 7739
45	(HPO:0002663)	Delayed epiphyseal ossification		21 / 7739
46	(HPO:0010579)	Cone-shaped epiphysis	Occasional [Orphanet]	54 / 7739
47	(HPO:0003026)	Short long bone		51 / 7739
48	(HPO:0002657)	Spondylometaphyseal dysplasia		12 / 7739
49	(HPO:0005616)	Accelerated skeletal maturation	Occasional [Orphanet]	46 / 7739
50	(HPO:0002750)	Delayed skeletal maturation	Very frequent [Orphanet]	250 / 7739
51	(HPO:0005280)	Depressed nasal bridge		381 / 7739
52	(HPO:0000358)	Posteriorly rotated ears		163 / 7739
53	(HPO:0001582)	Redundant skin		51 / 7739
54	(HPO:0002536)	Abnormal cortical gyration	Occasional [Orphanet]	72 / 7739
55	(HPO:0000007)	Autosomal recessive inheritance		2538 / 7739
56	(HPO:0001522)	Death in infancy	Very frequent [Orphanet]	275 / 7739
57	(HPO:0007187)	Focal lissencephaly		1 / 7739
58	(HPO:0002132)	Porencephaly		18 / 7739
59	(MedDRA:10072883)	Brachydactyly		153 / 7739
60	(OMIM)	Birth weight normal		14 / 7739
61	(OMIM)	Disproportionately small occipital bone		1 / 7739
62	(OMIM)	Irregular ossified ischia		1 / 7739
63	(OMIM)	Irregular scapulae		1 / 7739
64	(OMIM)	Medial and lateral spur		2 / 7739
65	(OMIM)	Small, narrow chest		1 / 7739
66	(OMIM)	Subacute myocarditis		1 / 7739
67	(OMIM)	Wide sacrosciatic notch		2 / 7739

Associated genes:

GPX4 (PMID:24706940)

ClinVar (via SNiPA)

Gene symbol	Variation	Clinical significance	Reference

Additional Information:

Clinical Description OMIM

Sedaghatian (1980) described an Iranian family with 3 sibs, 2 boys and a girl, with severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly. All 3 died in the first days of life of 'cardiorespiratory ...Sedaghatian (1980) described an Iranian family with 3 sibs, 2 boys and a girl, with severe metaphyseal chondrodysplasia, mild rhizomelic shortness of the upper limbs, and mild platyspondyly. All 3 died in the first days of life of 'cardiorespiratory insufficiency.' The one studied biochemically showed hypocalcemia, hyperphosphatemia, and elevated serum alkaline phosphatase. Autopsy in the same infant showed pulmonary, renal and adrenal hemorrhage, subendocardial myocarditis, and myocardial necrosis. Parental consanguinity was denied. Opitz et al. (1987) reported a second Iranian family, in which 2 males were affected; the parents were related as first cousins. In the offspring of a young black couple related as first cousins (with no known Iranian ancestry), Peeden et al. (1992) observed a third instance of this lethal form of spondylometaphyseal dysplasia. The male infant developed complete heart block in the newborn period; there was no evidence of systemic lupus erythematosus in the mother. He died at 2.5 days of age. Elcioglu and Hall (1998) presented the radiologic findings in 2 unrelated patients with the Sedaghatian type of spondylometaphyseal dysplasia. From a review of cases, they concluded that disproportionately long fibulas, disharmonious maturation, and turricephaly are usual features. Koutouby et al. (2000) reported a case of this disorder in an infant born to nonconsanguineous Yemeni parents. Although all previously reported cases had died within 4 days of life, this patient survived 161 days. The patient was profoundly hypotonic, and MRI of the brain showed grossly abnormal cortical development with lack of myelination of the underlying white matter. The ribs showed a V-shaped border at the posterior ends. English et al. (2006) reported a female infant, born to nonconsanguineous Caucasian parents, who had severe metaphyseal dysplasia with platyspondyly and V-shaped notching of the posterior ribs. The infant was hypotonic and experienced recurrent cyanotic episodes within a few hours of delivery; she developed seizures at day 14 and died at 17 days of age after experiencing increasingly frequent prolonged apneic episodes. Brain MRI revealed absence of the corpus callosum and marked frontotemporal pachygyria, providing further support for the existence of neuronal migration abnormalities in Sedaghatian spondylometaphyseal dysplasia. Aygun et al. (2012) studied a male infant, born to first-cousin Turkish parents, who presented with metaphyseal dysplasia, congenital atrioventricular block, simplified gyral pattern, hypogenesis of the corpus callosum, and severe cerebellar hypoplasia. He was the first-born child to a mother who had experienced 4 molar pregnancies and 2 first-trimester abortions. The infant was hypotonic and mechanically ventilated, with no sucking or gag reflexes, and died at 120 days of life. Aygun et al. (2012) proposed that central nervous system malformations might be a major component of the disorder and could be responsible for the hypotonicity, seizures, and respiratory failure observed in these patients

Symptoms & Signs

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