Trisomia 18 o sindrome di Edwards
Generalità
La trisomia 18 o sindrome di Edwards è un’ anomalia cromosomica caratterizzata dalla presenza di un cromosoma 18 in sovrannumero. La trisomia 18 o sindrome di Edwards fu descritta per la prima volta da Edwards nel 1960. L’incidenza della malattia è stimata in circa 1/6000-1/8000. Oltre il 95% dei feti affetti da trisomia 18 o sindrome di Edwards muore in utero. Per motivi non noti, il tasso di sopravvivenza è più alto nelle femmine rispetto ai maschi, con una predominanza delle femmine tra i soggetti nati vivi con trisomia 18. Il genotipo è variabile: nell’80% dei casi è dovuta ad una trisomia libera, causata dalla non disgiunzione meiotica per lo più materna; nel 10-15% è presente un mosaicismo, dovuto alla non disgiunzione post-zigotica. Il rimanente è dovuto ad una traslocazione robertsoniana. La Trisomia 18 in mosaico è stata osservata in alcuni pazienti che presentano un quadro clinico che varia dalla forma classica di trisomia 18 a fenotipo normale.
Quadro clinico nella Trisomia 18 o sindrome di Edwards
Il quadro clinico è caratterizzato da grave ritardo mentale e dalla crescita pre e post-natale con aspetto:
- emaciato
- ipotrofia
- microcefalia (con cranio piccolo)
- dolicocefalia (forma allungata e stretta del cranio, anomalie della faccia e della testa)
- micrognazia (sviluppo anomalo della mandibola, che appare di volume e dimensioni ridotti)
- ipertelorismo (deformazione cranica che distanzia le due orbite oculari,)
- ipoplasia (sviluppo anormale, incompleto o ridotto di un organo)
- orecchie angolate
- anomalie degli arti
- colonna vertebrale ricurva
- scoliosi
- grave ritardo psicomotorio
Anomalie dei piedi:
- piede equino/varo o a picozza, con sovrapposizione delle dita, il quinto e il secondo dito ricoprono il quarto e il terzo.
Nelle prime settimane di vita sono presenti:
- ipotonia
- iperreattività
- difficoltà alimentari (scarsa suzione).
Si possono presentare inoltre:
- malformazioni cardiache nel 90% dei casi;
- anomalie del tubo digerente (diastasi dei retti, ernia inguinale/ombelicale);
- anomalie genito-urinarie, agenesia renale ( mancanza di uno o entrambi i reni)
Diagnosi prenatale
In epoca prenatale sono presenti segni di sospetto quali:
- polidramnios
- placenta piccola
- ritardo di crescita
- malformazioni
- cisti multiple dei plessi corioidei
- scarsi movimenti fetali
- presentazione podalica
Alla nascita i segni possono essere:
- basso peso
- necessità di rianimazione neonatale
- basso indice di Apgar
- pianto debole
- ipotonia
Diagnosi della trisomia 18 o sindrome di Edwards
La diagnosi può essere confermata dall’esame citogenetico. Il rischio di ricorrenza di trisomia 18 nelle famiglie con un caso è di circa 1%. Tuttavia, nelle famiglie nelle quali la trisomia 18 è causata da una traslocazione, il rischio di ricorrenza è maggiore, in particolare se un genitore è portatore di una traslocazione bilanciata. La diagnosi prenatale può essere sospettata con l’evidenza ecografica dei segni prenatali e può essere confermata con l’analisi del cariotipo fetale. Anche i marcatori sierici utilizzati per la diagnosi di trisomia 21 possono essere alterati. La presa in carico è solo di supporto e deve essere multidisciplinare.
Trattamento
Il trattamento chirurgico delle malformazioni riesce a migliorare solo minimamente la prognosi infausta di questa sindrome. Il 90% dei bambini muore nel primo anno di vita a causa delle complicazioni cardiache, renali o neurologiche o delle infezioni ricorrenti. La sopravvivenza dipende soprattutto dal tipo di anomalia cromosomica, dalla gravità e dalla compatibilità con la vita delle malformazioni presenti. Sono stati osservati pazienti sopravvissuti in alcuni casi fino all’età adulta, soprattutto in presenza di trisomia in mosaico o in trisomia parziale (secondaria a traslocazione). La maggioranza dei pazienti non in mosaico sviluppa un’ autonomia molto limitata (assenza del linguaggio e della deambulazione). Il ritardo della crescita è significativo.
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