Colagenopatías tipo 2

Transcripción

1 Colagenopatías tipo 2 Fernando Santos Simarro INGEMM-Instituto de Genética Médica y Molecular UMDE-Unidad Multidisciplinar de Displasias Esqueléticas Hospital Universitario La Paz-IdiPAZ-CIBERER Madrid, 27 de Mayo de 2017

2 Colagenopatías tipo 2 Causadas por mutaciones en heterocigosis en el gen COL2A1. Herencia autosómica dominante. Clínicamente heterogéneas (desde formas letales hasta supervivencia normal). Talla baja desproporcionada. Degeneración articular. Manifestaciones extra esqueléticas comunes: Hendidura de paladar. Afectación ocular (miopía, desprendimiento retina, anomalías vítreo, cataratas, ). Pérdida auditiva.

3 COL2A1 12q coding exons 5071bp 1487aa

4 Heinegård D and Saxne T. Nature Reviews Rheumatology 2011)

5 Colagenopatías tipo 2 Letales: Achondrogenesis type 2 / Hypochondrogenesis Platyspondylic dysplasia, Torrance type No letales con talla baja: Spondyloepiphyseal dysplasia congenita (SEDC) Kniest dysplasia Spondyloepiphyseal dysplasia with marked metaphyseal changes (Strudwick type) Spondyloperipheral dysplasia Dysspondyloenchondromatosis No letales sin talla baja: Stickler dysplasia type 1 SED with metatarsal shortening (Czech dysplasia) Dysplasia of the proximal femoral epiphyses

6 Achondrogenesis type 2 / Hypochondrogenesis Missense mutations in the triple helical domain: Gly substitutions. Clinical features Micromelia Short trunk, proportionate abdomen Micrognathia; cleft palate Hydropic apperance Radiological features Absent retarded ossification of vertebral bodies Very short tubular bones Small iliac bones Absent/severely retarded ossifications of pubic and ischial bones. Differential diagnosis: Achondrogeneiss type 1A (TRIP11) / 1B (DTDST).

7 IMAGEN

8 Platyspondylic dysplasia Torrance Type Missense mutations in the carboxypropeptide. Normally lethal. Radiological features Severe platyspondyly. Broad ischial and pubic bones Zank et al. AJMG 2005

9 Type 2 collagenopathies Lethal Achondrogenesis type 2 / Hypochondrogenesis Platyspondylic dysplasia, Torrance type Non lethal with short stature Spondyloepiphyseal dysplasia congenita (SEDC) Kniest dysplasia Spondyloepiphyseal dysplasia with marked metaphyseal changes (Strudwick type) Spondyloperipheral dysplasia Dysspondyloenchondromatosis Non-lethal without short stature Stickler dysplasia type 1 SED with metatarsal shortening (formerly Czech dysplasia) Dysplasia of the proximal femoral epiphyses

10 SEDC Missense mutations (Gly), splicing mutations or in-frame deletions in the triple helical domain. Clinical features Short at birth (45cm) Flat face, prominente eyes, cleft palate (20%) Myopia, retinal detachment (less frequent than Stickler) Usually normal hands. Clubfeet Scoliosis, odontoid hypoplasia, coxa vara Radiological features At birth: absent ossification of pubic bone and distal femoral epiphysis. Absent/retarded ossification of cervical and sacral vertebrae Retarded epiphyseal ossification, then dysplastic. Metaphyseal involvment Preservation of hands. Flattened vertebral bodies. Coxa vara.

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15 Kniest dysplasia Features different from SEDC: More involvement of trunk. More frequency of cleft palate, hearing loss, myopia. Prominent joints. Hand involvement Large epiphyses. Spranger et al. AJMG 1997

16 Spondyloperipheral dysplasia Features different from SEDC: Short stature less pronounced Short hands / feet (metacarpals / metatarsals) Missense or frameshift mutations in the C-propeptide. Hand involvement Large epiphyses. Zank et al. AJMG 2004

17 Type 2 collagenopathies Lethal Achondrogenesis type 2 / Hypochondrogenesis Platyspondylic dysplasia, Torrance type Non lethal with short stature Spondyloepiphyseal dysplasia congenita (SEDC) Kniest dysplasia Spondyloepiphyseal dysplasia with marked metaphyseal changes (Strudwick type) Spondyloperipheral dysplasia Dysspondyloenchondromatosis Non-lethal without short stature Stickler dysplasia type 1 SED with metatarsal shortening (formerly Czech dysplasia) Dysplasia of the proximal femoral epiphyses

18 Stickler Clinical features Ocular: Myopia (severe) Retichal detachment Chorioretinal / vitreous degeneration. Cataracts / glaucoma. Orofacial: Cleft palate; submucous / Pierre-Robin Flat face, low nasal bridge. Auditory: Hearing loss (conductive / neursensorial / mixed). Osteoarticular: Joint pain Degenerative joint disease Mild hipermobility Vertebral abnormalities IMAGEN

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21 Czech dysplasia

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23 Recomendaciones seguimiento Oftalmología: Evaluación al diagnóstico (periodo neonatal) después anual o según precise. Tratamiento precoz. Evaluación audición (otoemisiones / potenciales). Hasta desarrollo lenguaje. Reparación quirúrgica hendidura paladar. Vigilar alimentación. Osteoarticular : Unión cráneo-cervical. Monitorizar caderas / columna. Evitar deportes contacto / obesidad. Asesoramiento genético. Evaluación multidisciplinar.