Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts

Mansour, Sahar, Josephs, Katherine S., Ostergaard, Pia ORCID: 0000-0002-2190-1356, Gordon, Kristiana, Van Zanten, Malou, Pearce, Julian, Jeffery, Steve, Keeley, Vaughan ORCID: 0000-0002-3004-2821, Riches, Katie, Kreuter, Alexander, Wieland, Ulrike, Haegerling, Rene, Ratnam, Lakshmi, Sackey, Ege, Grigoriadis, Dionysios ORCID: 0000-0002-9502-6590, Ho, Bernard, Smith, Frances, Rauter, Elisabeth, Mortimer, Peter and Macallan, Derek . Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts. J. Med. Genet.. LONDON: BMJ PUBLISHING GROUP. ISSN 1468-6244

Full text not available from this repository.

DOI:10.1136/jmedgenet-2021-107820

Abstract

Background Primary lymphoedema (PL) syndromes are increasingly recognised as presentations of complex genetic disease, with at least 20 identified causative genes. Recognition of clinical patterns is key to diagnosis, research and therapeutics. The defining criteria for one such clinical syndrome, 'WILD syndrome' (Warts, Immunodeficiency, Lymphoedema and anogenital Dysplasia), have previously depended on a single case report. Methods and results We present 21 patients (including the first described case) with similar clinical and immunological phenotypes. All had PL affecting multiple segments, with systemic involvement (intestinal lymphangiectasia/pleural or pericardial effusions) in 70% (n=14/20). Most (n=20, 95%) had a distinctive cutaneous lymphovascular malformation on the upper anterior chest wall. Some (n=10, 48%) also had hyperpigmented lesions resembling epidermal naevi (but probably lymphatic in origin). Warts were common (n=17, 81%) and often refractory. In contrast to the previous case report, anogenital dysplasia was uncommon-only found in two further cases (total n=3, 14%). Low CD4 counts and CD4:CD8 ratios typified the syndrome (17 of 19, 89%), but monocyte counts were universally normal, unlike GATA2 deficiency. Conclusion WILD syndrome is a previously unrecognised, underdiagnosed generalised PL syndrome. Based on this case series, we redefine WILD as 'Warts, Immunodeficiency, andLymphatic Dysplasia' and suggest specific diagnostic criteria. The essential criterion is congenital multisegmental PL in a 'mosaic' distribution. The major diagnostic features are recurrent warts, cutaneous lymphovascular malformations, systemic involvement (lymphatic dysplasia), genital swelling and CD4 lymphopaenia with normal monocyte counts. The absence of family history suggests a sporadic condition, and the random distribution of swelling implicates mosaic postzygotic mutation as the cause.

Item Type:

Journal Article

Creators:

Creators	Email	ORCID	ORCID Put Code
Mansour, Sahar	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Josephs, Katherine S.	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Ostergaard, Pia	UNSPECIFIED	orcid.org/0000-0002-2190-1356	UNSPECIFIED
Gordon, Kristiana	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Van Zanten, Malou	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Pearce, Julian	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Jeffery, Steve	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Keeley, Vaughan	UNSPECIFIED	orcid.org/0000-0002-3004-2821	UNSPECIFIED
Riches, Katie	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Kreuter, Alexander	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Wieland, Ulrike	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Haegerling, Rene	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Ratnam, Lakshmi	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Sackey, Ege	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Grigoriadis, Dionysios	UNSPECIFIED	orcid.org/0000-0002-9502-6590	UNSPECIFIED
Ho, Bernard	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Smith, Frances	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Rauter, Elisabeth	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Mortimer, Peter	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED
Macallan, Derek	UNSPECIFIED	UNSPECIFIED	UNSPECIFIED