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Smith-McCort dysplasia 2(SMC2)

MedGen UID:
811489
Concept ID:
C3714896
Disease or Syndrome
Synonym: SMC2
 
Gene (location): RAB33B (4q31.1)
 
Monarch Initiative: MONDO:0014087
OMIM®: 615222

Definition

Smith-McCort dysplasia is a rare autosomal recessive osteochondrodysplasia characterized by short trunk dwarfism with a barrel-shaped chest, rhizomelic limb shortening, and specific radiologic features including marked platyspondyly with double-humped end-plates, kyphoscoliosis, metaphyseal irregularities, laterally displaced capital femoral epiphyses, and small pelvis with a lace-like appearance of iliac crests. These clinical and radiologic features are also common to Dyggve-Melchior-Clausen syndrome (DMC; 223800), which is distinguished from SMC by the additional feature of mental retardation (summary by Dupuis et al., 2013). For a discussion of genetic heterogeneity of Smith-McCort dysplasia, see SMC1 (607326). [from OMIM]

Clinical features

From HPO
Pes planus
MedGen UID:
42034
Concept ID:
C0016202
Anatomical Abnormality
A foot where the longitudinal arch of the foot is in contact with the ground or floor when the individual is standing; or, in a patient lying supine, a foot where the arch is in contact with the surface of a flat board pressed against the sole of the foot by the examiner with a pressure similar to that expected from weight bearing; or, the height of the arch is reduced.
Genu valgum
MedGen UID:
154364
Concept ID:
C0576093
Anatomical Abnormality
The legs angle inward, such that the knees are close together and the ankles far apart.
Short phalanx of finger
MedGen UID:
163753
Concept ID:
C0877165
Finding
Short (hypoplastic) phalanx of finger, affecting one or more phalanges.
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.
Broad metatarsal
MedGen UID:
330797
Concept ID:
C1842231
Finding
Increased side-to-side width of a metatarsal bone.
Broad femoral neck
MedGen UID:
376496
Concept ID:
C1849016
Finding
An abnormally wide femoral neck (which is the process of bone, connecting the femoral head with the femoral shaft).
Short metatarsal
MedGen UID:
341358
Concept ID:
C1849020
Finding
Diminished length of a metatarsal bone, with resultant proximal displacement of the associated toe.
Broad phalanx
MedGen UID:
340809
Concept ID:
C1855185
Finding
Increased side-to-side width of one or more phalanges of the fingers or toes.
Enlarged interphalangeal joints
MedGen UID:
347212
Concept ID:
C1859701
Finding
Flattened femoral head
MedGen UID:
348146
Concept ID:
C1860601
Finding
An abnormally flattened femoral head.
Limited elbow extension
MedGen UID:
401158
Concept ID:
C1867103
Finding
Limited ability to straighten the arm at the elbow joint.
Prominent calcaneus
MedGen UID:
866740
Concept ID:
C4021088
Anatomical Abnormality
Protruding heel bone, or calcaneus.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Decreased body weight
MedGen UID:
1806755
Concept ID:
C5574742
Finding
Abnormally low body weight.
Intellectual disability
MedGen UID:
811461
Concept ID:
C3714756
Mental or Behavioral Dysfunction
Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.
Hyperlordosis
MedGen UID:
9805
Concept ID:
C0024003
Finding
Abnormally increased curvature (anterior concavity) of the lumbar or cervical spine.
Pectus carinatum
MedGen UID:
57643
Concept ID:
C0158731
Finding
A deformity of the chest caused by overgrowth of the ribs and characterized by protrusion of the sternum.
Barrel-shaped chest
MedGen UID:
120497
Concept ID:
C0264172
Finding
A rounded, bulging chest that resembles the shape of a barrel. That is, there is an increased anteroposterior diameter and usually some degree of kyphosis.
Metaphyseal irregularity
MedGen UID:
325478
Concept ID:
C1838662
Finding
Irregularity of the normally smooth surface of the metaphyses.
Platyspondyly
MedGen UID:
335010
Concept ID:
C1844704
Finding
A flattened vertebral body shape with reduced distance between the vertebral endplates.
Disproportionate short-trunk short stature
MedGen UID:
337580
Concept ID:
C1846435
Finding
A type of disproportionate short stature characterized by a short trunk but a average-sized limbs.
Odontoid hypoplasia
MedGen UID:
339524
Concept ID:
C1846439
Finding
The odontoid process, or dens, is a bony projection from the axis (C2) upward into the ring of the atlas (C1) at the top of the spine. During embryogenesis, the body of the odontoid derives from the centrum of the atlas and separates from the atlas, fusing with the superior portion of the axis. If the odontoid is hypoplastic or absent, the attachments for the apical and alar ligaments are missing, allowing for excessive rotation of the atlas, craniocervical instability, and possibly cord compression (summary by Stevens et al., 2009).
Flattened epiphysis
MedGen UID:
387844
Concept ID:
C1857527
Finding
Abnormal flatness (decreased height) of epiphyses.
Mandibular prognathia
MedGen UID:
98316
Concept ID:
C0399526
Finding
Abnormal prominence of the chin related to increased length of the mandible.
Short neck
MedGen UID:
99267
Concept ID:
C0521525
Finding
Diminished length of the neck.
Coarse facial features
MedGen UID:
335284
Concept ID:
C1845847
Finding
Absence of fine and sharp appearance of brows, nose, lips, mouth, and chin, usually because of rounded and heavy features or thickened skin with or without thickening of subcutaneous and bony tissues.

Recent clinical studies

Etiology

Akalın A, Ayaz E, Soğukpınar M, Avcı-Durmuşalioğlu E, Ürel-Demir G, Yıldız AE, Atik T, Elcioglu NH, Eda Utine G, Şimşek-Kiper PÖ
Am J Med Genet A 2024 Oct;194(10):e63785. Epub 2024 Jun 11 doi: 10.1002/ajmg.a.63785. PMID: 38860472
Varshney K, Narayanachar SG, Girisha KM, Bhavani GS, Narayanan D, Phadke S, Nampoothiri S, Udupi GA, Raghupathy P, Nair M, Geetha TS, Bhat M
J Med Genet 2023 Feb;60(2):204-211. Epub 2022 Apr 27 doi: 10.1136/jmedgenet-2021-108098. PMID: 35477554

Diagnosis

Akalın A, Ayaz E, Soğukpınar M, Avcı-Durmuşalioğlu E, Ürel-Demir G, Yıldız AE, Atik T, Elcioglu NH, Eda Utine G, Şimşek-Kiper PÖ
Am J Med Genet A 2024 Oct;194(10):e63785. Epub 2024 Jun 11 doi: 10.1002/ajmg.a.63785. PMID: 38860472
Holling T, Bhavani GS, von Elsner L, Shah H, Kausthubham N, Bhattacharyya SS, Shukla A, Mortier GR, Schinke T, Danyukova T, Pohl S, Kutsche K, Girisha KM
Hum Mutat 2022 May;43(5):625-642. Epub 2022 Mar 21 doi: 10.1002/humu.24368. PMID: 35266227
Tüysüz B, Geyik F, Yıldırım T, Alkaya DU, Sharifova S, Kafadar A
Eur J Med Genet 2021 Jul;64(7):104248. Epub 2021 May 14 doi: 10.1016/j.ejmg.2021.104248. PMID: 34000439
Dupuis N, Lebon S, Kumar M, Drunat S, Graul-Neumann LM, Gressens P, El Ghouzzi V
Hum Mutat 2013 Feb;34(2):283-6. Epub 2012 Nov 8 doi: 10.1002/humu.22235. PMID: 23042644

Prognosis

Akalın A, Ayaz E, Soğukpınar M, Avcı-Durmuşalioğlu E, Ürel-Demir G, Yıldız AE, Atik T, Elcioglu NH, Eda Utine G, Şimşek-Kiper PÖ
Am J Med Genet A 2024 Oct;194(10):e63785. Epub 2024 Jun 11 doi: 10.1002/ajmg.a.63785. PMID: 38860472

Clinical prediction guides

Akalın A, Ayaz E, Soğukpınar M, Avcı-Durmuşalioğlu E, Ürel-Demir G, Yıldız AE, Atik T, Elcioglu NH, Eda Utine G, Şimşek-Kiper PÖ
Am J Med Genet A 2024 Oct;194(10):e63785. Epub 2024 Jun 11 doi: 10.1002/ajmg.a.63785. PMID: 38860472
Okaya T, Kawasaki T, Sato S, Koyanagi Y, Tatsumi K, Hatano R, Ohnuma K, Morimoto C, Kasuya Y, Hasegawa Y, Ohara O, Suzuki T
Int J Mol Sci 2024 Jan 6;25(2) doi: 10.3390/ijms25020748. PMID: 38255821Free PMC Article
Tüysüz B, Geyik F, Yıldırım T, Alkaya DU, Sharifova S, Kafadar A
Eur J Med Genet 2021 Jul;64(7):104248. Epub 2021 May 14 doi: 10.1016/j.ejmg.2021.104248. PMID: 34000439

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