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Inquadramento e work-up diagnostico – isolata o
sindromica?
Dott.ssa Silvia Maitz
Ambulatorio di Genetica Pediatrica
Clinica Pediatrica - Fondazione MBBM
AO S. Gerardo di Monza
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MALFORMAZIONI(1/40 BAMBINI)
ISOLATE ASSOCIATE AD ALTRE
MALFORMAZIONI,
ANOMALIE O
PROBLEMATICHE
SINDROME
GENETICA
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Una malformazione è isolata
fino a prova contraria
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Malformazioni maggiori e sindromi
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“Se lo conosci lo riconosci”
Il sospetto diagnostico
di una malattia rara
può venire quando la
si cerca
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Strumentiper la
diagnosi
• Clinici: anamnesi, esame obiettivo, studio del caso
• Di laboratorio: test genetici (in questo caso analisi molecolari)
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Come si svolge la visita?
1. Anamnesi
2. Esame obiettivo
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Anamnesi
• Familiare• Gravidica• Neonatale• Fisiologica• Patologica • Ricognizione dei test
e delle valutazioni strumentali e cliniche effettuate
Non anamnesi particolare ma raccolta con un’attenzione particolare
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Anamnesi familiare
• Ricostruzione dell’albero genealogico di 3 generazioni
• Potenziale indicatore di:
- ricorrenza familiare
- modalità di segregazione
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Esame obiettivo
�Colore dei capelli: ciuffo bianco, incanutimento precoce�Forma del volto e del cranio�Sinofria �Occhi: colore (eterocromia), posizione, DII e DIE,
cristallino, retina�Orecchie: pits/tags, forma, dimensioni e impianto pad aur,
anomalie MAE�Regione orale: labiopalatoschisi, anomalie dentarie �Collo: anomalie branchiali, gozzo�Cute: iper/ipopigmentazione, CLS, cheratodermia �Dita: poli/oligodattilia, dimensioni, forma�Accrescimento(iposomia, macrosomia)�Valutazione neurologica: cammino, equilibrio
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Sistemi computerizzati
• Oxford Medical Database(Dysmorphology and Neurogenetics)
• POSSUM
Sistemi per espertiNON sistemi esperti
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Diagnosi differenziali• Sindrome Proteus: crescita incontrollata di pelle,
ossa e tessuti (compresi vasi sanguigni e linfatici) in varie parti del corpo
• Sclerosi tuberosa: mutazione dei geni TSC1 o TSC2; amartomi a carico del tessuto cerebrale, della cute, dei reni, dei polmoni, del cuore
• Mutazioni del gene PTEN
• Neurofibromatosi di tipo I
• Sindrome di Klippel – Trenaunay
• …
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Neuroma paciniano
Sindrome di Maffucci
Sindrome di Klippel -Trenaunay
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PIK3CA-related overgrowth spectrum (PROS)
• Iperplasia fibroadiposa (FAO)
• Emiperplasia
• Emimegalencefalia
• Macrodattilia
• Sindrome CLOVES: congenital lipomatous asymmetric overgrowth of the trunk, lymphatic, capillary, venous, and combined-type vascular malformations, epidermal nevi, skeletal and spinal anomalies
• Sindrome emiperplasia – lipomatosi multipla (HHML)
• Megalencefalia – malformazioni capillari (MCAP)
SONO TUTTE FORME A MOSAICO!
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Rx
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Non diagnosi specifica
Pz non sindromicoPz verosimilmentesindromico ma non inquadrabile
Follow-up nel tempo(periodicità in relazioneall’età)
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Cosa può accadere nel tempo ?
1. Evoluzione fenotipica del paziente
2. Comparsa di nuovi segni clinici ad insorgenza età-dipendente
3. Definizione di nuove tecnologie di studio del patrimonio genetico
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La prognosi e le opzioni terapeutiche dipendono dalla diagnosi di base
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Cause genetiche
Congenito
EreditarioGenetico
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PIK3CA � macrodattilia
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Perché una diagnosi ?
Aspetti positivi:Percorso diagnostico semplificatoDefinizione della prognosiImpostazione di un programma specifico di follow-up (rischio tumorale?)
Consulenza genetica per i genitoriPotenziale contatto con associazione di genitori
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