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Spondylometaphyseal dysplasia, Sedaghatian type(SMDS)

MedGen UID:
340816
Concept ID:
C1855229
Disease or Syndrome
Synonyms: Lethal metaphyseal dysplasia; METAPHYSEAL CHONDRODYSPLASIA, CONGENITAL LETHAL; SEDAGHATIAN CHONDRODYSPLASIA
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): GPX4 (19p13.3)
 
Monarch Initiative: MONDO:0009593
OMIM®: 250220
Orphanet: ORPHA93317

Definition

Sedaghatian-type spondylometaphyseal dysplasia (SMDS) is a rare lethal disorder characterized by severe metaphyseal chondrodysplasia with mild limb shortening, platyspondyly, delayed epiphyseal ossification, irregular iliac crests, and pulmonary hemorrhage. Affected infants present with severe hypotonia and cardiorespiratory problems; most die within days of birth due to respiratory failure. Cardiac abnormalities include conduction defects, complete heart block, and structural anomalies. Half of infants with SMDS are reported to have central nervous system malformations consistent with abnormal neuronal migration, including agenesis of the corpus callosum, pronounced frontotemporal pachygyria, simplified gyral pattern, partial lissencephaly, and severe cerebellar hypoplasia (summary by Smith et al., 2014). [from OMIM]

Clinical features

From HPO
Clubfoot
MedGen UID:
3130
Concept ID:
C0009081
Congenital Abnormality
Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).
Brachydactyly
MedGen UID:
67454
Concept ID:
C0221357
Congenital Abnormality
Digits that appear disproportionately short compared to the hand/foot. The word brachydactyly is used here to describe a series distinct patterns of shortened digits (brachydactyly types A-E). This is the sense used here.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
Short toe
MedGen UID:
322858
Concept ID:
C1836195
Finding
A toe that appears disproportionately short compared to the foot.
Short metacarpal
MedGen UID:
323064
Concept ID:
C1837084
Anatomical Abnormality
Diminished length of one or more metacarpal bones in relation to the others of the same hand or to the contralateral metacarpal.
Flat acetabular roof
MedGen UID:
373340
Concept ID:
C1837485
Finding
Flattening of the superior part of the acetabulum, which is a cup-shaped cavity at the base of the hipbone into which the ball-shaped head of the femur fits. The acetabular roof thereby appears horizontal rather than arched, as it normally does.
Short finger
MedGen UID:
334977
Concept ID:
C1844548
Anatomical Abnormality
Abnormally short finger associated with developmental hypoplasia.
Long fibula
MedGen UID:
338386
Concept ID:
C1848109
Finding
Disproportionately long fibulae.
Irregular tarsal bones
MedGen UID:
381591
Concept ID:
C1855240
Finding
Rhizomelia
MedGen UID:
357122
Concept ID:
C1866730
Congenital Abnormality
Disproportionate shortening of the proximal segment of limbs (i.e. the femur and humerus).
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
Atrial septal defect
MedGen UID:
6753
Concept ID:
C0018817
Congenital Abnormality
Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.
Myocarditis
MedGen UID:
44553
Concept ID:
C0027059
Disease or Syndrome
Inflammation of the myocardium.
Disproportionate short stature
MedGen UID:
168053
Concept ID:
C0878659
Finding
A kind of short stature in which different regions of the body are shortened to differing extents.
Posteriorly rotated ears
MedGen UID:
96566
Concept ID:
C0431478
Congenital Abnormality
A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front).
Focal lissencephaly
MedGen UID:
344450
Concept ID:
C1855230
Congenital Abnormality
A congenital absence of the convolutions of the cerebral cortex and a poorly formed sylvian fissure that affects a particular part of the cortex.
Porencephalic cyst
MedGen UID:
906044
Concept ID:
C4082172
Disease or Syndrome
A cavity within the cerebral hemisphere, filled with cerebrospinal fluid, that communicates directly with the ventricular system.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Narrow chest
MedGen UID:
96528
Concept ID:
C0426790
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Short ribs
MedGen UID:
98094
Concept ID:
C0426817
Finding
Reduced rib length.
Narrow greater sciatic notch
MedGen UID:
154353
Concept ID:
C0566888
Finding
A narrowing of the sacrosciatic notch, i.e., the deep indentation in the posterior border of the hip bone at the point of union of the ilium and ischium.
Metaphyseal cupping
MedGen UID:
323062
Concept ID:
C1837082
Finding
Metaphyseal cupping refers to an inward bulging of the metaphyseal profile giving the metaphysis a cup-like appearance.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
11 pairs of ribs
MedGen UID:
326950
Concept ID:
C1839731
Finding
Presence of only 11 pairs of ribs.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Short long bone
MedGen UID:
344385
Concept ID:
C1854912
Finding
One or more abnormally short long bone.
Large posterior fontanelle
MedGen UID:
340819
Concept ID:
C1855233
Finding
An enlargement of the posterior fontanelle relative to age-dependent norms.
Cone-shaped metacarpal epiphyses
MedGen UID:
343300
Concept ID:
C1855239
Finding
A cone-shaped appearance of the epiphyses of the metacarpal bones, producing a 'ball-in-a-socket' appearance. This epiphyses are located at the distal ends of the metacarpal bones.
Iliac crest serration
MedGen UID:
387761
Concept ID:
C1857186
Finding
Irregularities of the iliac crest that produce the appearance of a lace border around it.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Cone-shaped epiphyses of the phalanges of the hand
MedGen UID:
347156
Concept ID:
C1859480
Finding
A cone-shaped appearance of the epiphyses of the fingers of the hand, producing a 'ball-in-a-socket' appearance. The related entity 'angel-shaped' epiphysis refers to a pronounced cone-shaped epiphysis in combination with a pseudoepiphysis at the distal end of a phalanx.
Cupped ribs
MedGen UID:
351284
Concept ID:
C1865039
Finding
Wide, concave rib end.
Delayed epiphyseal ossification
MedGen UID:
351324
Concept ID:
C1865200
Finding
Flared iliac wing
MedGen UID:
356097
Concept ID:
C1865841
Finding
Widening of the ilium ala, that is of the wing of the ilium, combined with external rotation, leading to a flared appearance of the iliac wing.
Horizontal inferior border of scapula
MedGen UID:
812841
Concept ID:
C3806511
Finding
A morphological abnormality of the scapula in which there is a flat (horizontal) inferior edge of the scapula. The entire scapula is said to resemble a square, leading to the designation sqaring of the scapula (in Figure 1 of PMID:24706940 the scapulae have a roughly rectangular shape).
Widened greater sciatic notch
MedGen UID:
870186
Concept ID:
C4024620
Anatomical Abnormality
The sacroiliac joint in the bony pelvis connects the sacrum and the ilium of the pelvis, which are joined by strong ligaments. The notch is located directly superior to the joint. This term refers to a increase in the lateral dimension of the notch.
Spondylometaphyseal dysplasia
MedGen UID:
1674850
Concept ID:
C4759767
Disease or Syndrome
A heterogeneous group of disorders associated with walking and growth disturbances that become evident during the second year of life. Characteristics are platyspondyly (flattened vertebrae) and marked hip and knee metaphyseal lesions. The different forms of spondylometaphyseal dysplasia are distinguished by the localisation and severity of involvement of the affected metaphyses.
Turricephaly
MedGen UID:
1726910
Concept ID:
C5399823
Congenital Abnormality
Tall head relative to width and length.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Depressed nasal bridge
MedGen UID:
373112
Concept ID:
C1836542
Finding
Posterior positioning of the nasal root in relation to the overall facial profile for age.
Redundant skin
MedGen UID:
154379
Concept ID:
C0581342
Pathologic Function
Loose and sagging skin often associated with loss of skin elasticity.

Recent clinical studies

Diagnosis

Fedida A, Ben Harouch S, Kalfon L, Abunassar Z, Omari H, Mandel H, Falik-Zaccai TC
Eur J Med Genet 2020 Nov;63(11):104020. Epub 2020 Aug 20 doi: 10.1016/j.ejmg.2020.104020. PMID: 32827718
Aygun C, Celik FC, Nural MS, Azak E, Kucukoduk S, Ogur G, Incesu L
Am J Med Genet A 2012 Jun;158A(6):1400-5. Epub 2012 Apr 23 doi: 10.1002/ajmg.a.35306. PMID: 22529034
Mahendran SM, Wilcox FL, Chirumamila L
J Obstet Gynaecol 2007 Nov;27(8):851-3. doi: 10.1080/01443610701803701. PMID: 18097914
Elçioglu N, Hall CM
Am J Med Genet 1998 Apr 13;76(5):410-4. PMID: 9556300
Peeden JN Jr, Rimoin DL, Lachman RS, Dyer ML, Gerard D, Gruber HE
Am J Med Genet 1992 Nov 15;44(5):651-6. doi: 10.1002/ajmg.1320440525. PMID: 1481828

Therapy

Peeden JN Jr, Rimoin DL, Lachman RS, Dyer ML, Gerard D, Gruber HE
Am J Med Genet 1992 Nov 15;44(5):651-6. doi: 10.1002/ajmg.1320440525. PMID: 1481828

Prognosis

Aygun C, Celik FC, Nural MS, Azak E, Kucukoduk S, Ogur G, Incesu L
Am J Med Genet A 2012 Jun;158A(6):1400-5. Epub 2012 Apr 23 doi: 10.1002/ajmg.a.35306. PMID: 22529034
Mahendran SM, Wilcox FL, Chirumamila L
J Obstet Gynaecol 2007 Nov;27(8):851-3. doi: 10.1080/01443610701803701. PMID: 18097914
Kerr B, Smith V, Patel R, Ladusans E, Sillence DO
Clin Dysmorphol 2000 Jul;9(3):167-72. doi: 10.1097/00019605-200009030-00003. PMID: 10955475
Elçioglu N, Hall CM
Am J Med Genet 1998 Apr 13;76(5):410-4. PMID: 9556300
Peeden JN Jr, Rimoin DL, Lachman RS, Dyer ML, Gerard D, Gruber HE
Am J Med Genet 1992 Nov 15;44(5):651-6. doi: 10.1002/ajmg.1320440525. PMID: 1481828

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