Department of Dermatology, Reference Centre for Genodermatoses and Rare Skin Diseases (MAGEC), Necker-Enfants Malades Hospital (AP-HP), Imagine Institute, Paris, France.
Paris-Centre University, Paris, France.
Br J Dermatol. 2021 Mar;184(3):532-537. doi: 10.1111/bjd.19265. Epub 2020 Sep 10.
Netherton syndrome (NS) is a rare disease caused by SPINK5 mutations, featuring variable skin and hair involvement and, in many cases, allergic manifestations with a risk of lethality, particularly in infants. The clinical management of NS is challenging.
To analyse the clinical manifestations of a cohort of infants with NS managed in a reference centre and to draw up recommendations for management.
We conducted a monocentric analysis of patients with NS. The inclusion criteria were management in our reference centre, a histologically or molecularly confirmed diagnosis of NS and available epidemiological, clinical and laboratory data.
A total of 43 patients with NS were included. Hypernatraemia was reported in 23 cases (54%) and associated with a greater likelihood of enteral and/or parenteral nutritional support (P < 0.001). Moreover, hypernatraemia was more frequent in patients with skin manifestations at birth (P = 0.026) and in patients bearing the c.153delT mutation in SPINK5 exon 3 (P = 0.014). The need for enteral and/or parenteral nutritional support was associated with a history of hypernatraemic dehydration (P < 0.001). Several unexpected extracutaneous complications were recorded, and new mutations were reported. The death rate (9% overall) was higher among the subset of patients bearing the c.153delT deletion.
Our data emphasize that neonatal NS is a severe and sometimes lethal multisystem disorder. Patients have a high risk of variable metabolic anomalies (i.e. lethal hypernatraemia) and therefore have major nutritional needs. Cases of NS associated with c.153delT are particularly severe. Unexpected clinical manifestations broadened the phenotypic spectrum of NS. We provide recommendations on the management of the life-threatening manifestations of NS in neonates based on our multidisciplinary experience.
Netherton 综合征（NS）是一种由 SPINK5 突变引起的罕见疾病，其特征为皮肤和毛发受累的变异性，且在许多情况下伴有过敏表现，具有致死风险，尤其是在婴儿中。NS 的临床管理具有挑战性。
分析在一个参考中心管理的 NS 患儿队列的临床表现，并制定管理建议。
我们对 NS 患儿进行了单中心分析。纳入标准为在我们的参考中心接受管理、组织学或分子学确诊的 NS 以及具有可用的流行病学、临床和实验室数据。
共纳入 43 例 NS 患儿。23 例（54%）存在高钠血症，且更有可能需要肠内和/或肠外营养支持（P < 0.001）。此外，出生时存在皮肤表现的患儿（P = 0.026）和携带 SPINK5 外显子 3 中的 c.153delT 突变的患儿（P = 0.014）更常发生高钠血症。需要肠内和/或肠外营养支持与高钠血症性脱水的病史相关（P < 0.001）。记录到一些意外的皮肤外并发症，并报告了新的突变。c.153delT 缺失的患儿总体死亡率（9%）更高。
我们的数据强调，新生儿 NS 是一种严重且有时致命的多系统疾病。患儿存在各种代谢异常（即致命性高钠血症）的高风险，因此有重大的营养需求。携带 c.153delT 的 NS 病例尤其严重。意想不到的临床表现拓宽了 NS 的表型谱。根据我们的多学科经验，我们就新生儿 NS 危及生命的表现的管理提供建议。
