Medicine:Sponastrime dysplasia
| Sponastrime dysplasia | |
|---|---|
 | |
| This condition is inherited in an autosomal recessive manner. | |
| Specialty | Medical genetics |
| Causes | Mutations in the TONSL gene |
Sponastrime dysplasia is a rare condition characterised by facial and skeletal abnormalities.[1][2]
Signs and symptoms
The main features of this condition are evident in skeleton and face.[3]
Facial features:
- Macrocephaly
- Frontal bossing
- Midface hypoplasia
- Depressed nasal root
- Small upturned nose
- Prognathism
Skeletal features:
- Shortened limbs (more pronounced in lower limbs)
- Short stature
- Progressive coxa vara
On X ray:
- Abnormal vertebral bodies (particularly in the lumbar region)
- Avascular necrosis of the capital femoral epiphyses
- Striated metaphyses
- Generalized mild osteoporosis
- Delayed ossification of the carpal bones
Other associated conditions:
These are variably present[4]
- Cataracts
- Hypogammaglobulinemia
- Intellectual disability
- Short dental roots
- Subglottic stenosis
- Tracheobronchomalacia
Genetics
This condition has been associated with mutations in the Tonsoku-like, DNA repair protein (TONSL) gene.[5][6] This gene is located on the long arm of chromosome 8 (8q24.3). This gene is also known as NFKBIL2.[citation needed]
Pathopysiology
This is not understood. It appears that the TONSL gene product is involved in genome repair.[7]
Diagnosis
This can be suspected when the usual facial and skeletal features are present. It is confirmed by sequencing the TONSL gene.[citation needed]
Differential diagnosis
Short limbed dwarfism syndrome in association with immunodeficiency.[citation needed]
Treatment
There is no specific treatment for this condition. Management is supportive.[citation needed]
Epidemiology
This condition is considered to be rare with less than 100 cases reported in the literature.[citation needed]
History
This condition was first described in 1983.[8]
References
- ↑ Cooper HA, Crowe J, Butler MG (2000) Sponastrime dysplasia: report of an 11-year-old boy and review of the literature. Am J Med Genet 92: 33-39
- ↑ Gripp KW, Johnson C, Scott CI, Jr, Nicholson L, Bober M, Butler MG, Shaw L, Gorlin RJ (2008) Expanding the phenotype of SPONASTRIME dysplasia to include short dental roots, hypogammaglobulinemia, and cataracts. Am J Med Genet 146A: 468-473
- ↑ Langer LO Jr, Beals RK, LaFranchi S, Scott CI, Jr, Sockalosky JJ (1996) Sponastrime dysplasia: five new cases and review of nine previously published cases. Am J Med Genet 63: 20-27. Note: Erratum: Am. J Med Genet 65: 94 only 1996
- ↑ Slaney SF, Hall CM, Atherton DJ, Winter RM (1999) A new syndrome of spondyloepimetaphyseal dysplasia, eczema and hypogammaglobulinaemia. Clin Dysmorph 8: 79-85
- ↑ Chang HR, Cho SY, Lee JH, Lee E, Seo J, Lee HR, Cavalcanti DP, Mäkitie O, Valta H, Girisha KM, Lee C, Neethukrishna K, Bhavani GS, Shukla A, Nampoothiri S, Phadke SR, Park MJ, Ikegawa S, Wang Z, Higgs MR, Stewart GS, Jung E, Lee MS, Park JH, Lee EA, Kim H, Myung K, Jeon W, Lee K, Kim D, Kim OH, Choi M, Lee HW, Kim Y, Cho TJ (2019) Hypomorphic Mutations in TONSL Cause SPONASTRIME Dysplasia. Am J Hum Genet 104(3):439-453
- ↑ Burrage LC, Reynolds JJ, Baratang NV, Phillips JB, Wegner J, McFarquhar A, Higgs MR, Christiansen AE, Lanza DG, Seavitt JR, Jain M, Li X, Parry DA, Raman V, Chitayat D, Chinn IK, Bertuch AA, Karaviti L, Schlesinger AE, Earl D, Bamshad M, Savarirayan R, Doddapaneni H, Muzny D, Jhangiani SN, Eng CM, Gibbs RA, Bi W, Emrick L, Rosenfeld JA, Postlethwait J, Westerfield M, Dickinson ME, Beaudet AL, Ranza E, Huber C, Cormier-Daire V, Shen W, Mao R, Heaney JD, Orange JS; University of Washington Center for Mendelian Genomics; Undiagnosed Diseases Network, Bertola D, Yamamoto GL, Baratela WAR, Butler MG, Ali A, Adeli M30, Cohn DH31, Krakow D32, Jackson AP33, Lees M, Offiah AC, Carlston CM, Carey JC, Stewart GS, Bacino CA, Campeau PM, Lee B (2019) Bi-allelic Variants in TONSL Cause SPONASTRIME Dysplasia and a Spectrum of Skeletal Dysplasia Phenotypes. Am J Hum Genet 104(3):422-438
- ↑ O'Donnell L, Panier S, Wildenhain J, Tkach JM, Al-Hakim A, Landry MC, Escribano-Diaz C, Szilard RK, Young JT, Munro M, Canny MD, Kolas NK, Zhang W, Harding SM, Ylanko J, Mendez M, Mullin M, Sun T, Habermann B, Datti A, Bristow RG, Gingras AC, Tyers MD, Brown GW, Durocher D (2010) The MMS22L-TONSL complex mediates recovery from replication stress and homologous recombination. Mol Cell 40(4):619-631
- ↑ Fanconi CI, Giedion A, Prader A. (1983) The Sponastrime dysplasia: familial short-limb dwarfism with saddle nose, spinal alterations and metaphyseal striation. Helv Paediat Acta 38:267-280
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