Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.
Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts.
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DOI：
10.1136/jmedgenet-2021-107820
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发表时间：
2023-01
影响因子：
4
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原发性淋巴水肿 (PL) 综合征越来越被认为是复杂遗传性疾病的表现，至少有 20 个已确定的致病基因。识别临床模式是诊断、研究和治疗的关键。此类临床综合征“野生综合征”（疣、免疫缺陷、淋巴水肿和肛门生殖器发育不良）的定义标准以前依赖于单个病例报告。我们介绍了 21 名具有相似临床和免疫表型的患者（包括第一个描述的病例）。所有患者的 PL 均累及多个节段，70% 的患者出现全身受累（肠淋巴管扩张/胸膜或心包积液）（n=14/20）。大多数（n=20，95%）在上前胸壁有明显的皮肤淋巴管畸形。一些（n=10，48%）还具有类似于表皮痣的色素沉着过度病变（但可能起源于淋巴）。疣很常见（n=17, 81%）并且通常难以治疗。与之前的病例报告相比，肛门生殖器发育不良并不常见，仅在另外两例病例中发现（总数 n=3，14%）。 CD4 计数和 CD4:CD8 比率低是该综合征的典型特征（19 例中有 17 例，占 89%），但单核细胞计数普遍正常，与 GATA2 缺陷不同。 WILD 综合征是一种以前未被识别、诊断不足的全身性 PL 综合征。基于该病例系列，我们将 WILD 重新定义为“疣、免疫缺陷和淋巴发育不良”，并提出了具体的诊断标准。基本标准是“马赛克”分布的先天性多节段 PL。主要诊断特征是复发性疣、皮肤淋巴管畸形、全身受累（淋巴发育不良）、生殖器肿胀和单核细胞计数正常的 CD4 淋巴细胞减少。缺乏家族史表明其为散发性疾病，而肿胀的随机分布表明嵌合性合子后突变是其原因。
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. 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. 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.
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影响因子：
4
作者：
Gordon K;Varney R;Keeley V;Riches K;Jeffery S;Van Zanten M;Mortimer P;Ostergaard P;Mansour S
通讯作者：
Mansour S
影响因子：
4
作者：
Ansari M;Poke G;Ferry Q;Williamson K;Aldridge R;Meynert AM;Bengani H;Chan CY;Kayserili H;Avci S;Hennekam RC;Lampe AK;Redeker E;Homfray T;Ross A;Falkenberg Smeland M;Mansour S;Parker MJ;Cook JA;Splitt M;Fisher RB;Fryer A;Magee AC;Wilkie A;Barnicoat A;Brady AF;Cooper NS;Mercer C;Deshpande C;Bennett CP;Pilz DT;Ruddy D;Cilliers D;Johnson DS;Josifova D;Rosser E;Thompson EM;Wakeling E;Kinning E;Stewart F;Flinter F;Girisha KM;Cox H;Firth HV;Kingston H;Wee JS;Hurst JA;Clayton-Smith J;Tolmie J;Vogt J;Tatton-Brown K;Chandler K;Prescott K;Wilson L;Behnam M;McEntagart M;Davidson R;Lynch SA;Sisodiya S;Mehta SG;McKee SA;Mohammed S;Holden S;Park SM;Holder SE;Harrison V;McConnell V;Lam WK;Green AJ;Donnai D;Bitner-Glindzicz M;Donnelly DE;Nellåker C;Taylor MS;FitzPatrick DR
通讯作者：
FitzPatrick DR
影响因子：
1.9
作者：
Vignes, Stephane;Carcelain, Guislaine
通讯作者：
Carcelain, Guislaine
影响因子：
9.8
作者：
Fang, JM;Dagenais, SL;Glover, TW
通讯作者：
Glover, TW
影响因子：
--
作者：
OSTROW, RS;MANIAS, D;FARAS, AJ
通讯作者：
FARAS, AJ