Post on 03-Oct-2018
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
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.
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
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).
Platyspondylic dysplasia Torrance Type
• Missense mutations in the carboxy-propeptide.
• Normally lethal.
• Radiological features
• Severe platyspondyly.
• Broad ischial and pubic bones
Zank et al. AJMG 2005
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
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.
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
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
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
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
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.