Netherton syndrome caused by serine protease inhibitor of Kazal type 5 gene mutation: a case report and literature review / 中华围产医学杂志

ABSTRACT

Objective:To investigate the clinical and molecular genetic features of neonatal congenital Netherton syndrome (NS) caused by mutations in serine protease inhibitor of Kazal type 5 ( SPINK5) gene. Methods:This study retrospectively analyzed the clinical data of an NS neonate admitted to Shanghai Children's Hospital in November 2018. SPINK5 gene was analyzed using high-throughput sequencing and Sanger sequencing. Relevant articles were retrieved from various databases including China National Knowledge Infrastructure, Wanfang and PubMed, and the reported cases who were diagnosed as NS within two months after birth with SPINK5 gene sequencing results were reviewed. Clinical features, gene mutations, treatment and follow-up results of NS were summarized using descriptive statistical analysis. Results:The patient presented with diffuse erythema and desquamation, sparse hair and repeated infections shortly after birth. Laboratory tests revealed elevated IgE (111 IU/ml) and "invagination-like" change in the hair under optical microscope. SPINK5 gene analysis found that there were compound heterozygous mutations of c.2468dup (p.Lys824Glufs*4) and c.377_378del (p.Tys126*) in the child. The pedigree analysis found that the two mutations were respectively inherited from the father and the mother, which supported the diagnosis of NS caused by SPINK5 gene mutation. Though skin rash improved after comprehensive treatments including anti-infection therapy, gamma globulin injection and skincare, the patient suffered from recurrent infection and was discharged from the hospital after giving up treatment and died of infection at two months old. Eleven NS cases were retrieved from literature and altogether 12 cases were analyzed here. The most common clinical manifestations in the 12 patients were early skin diffuse erythema and desquamation (12/12), infection (8/12), dry hair (7/12), hypernatremia dehydration (7/12), high IgE (5/12), growth retardation (4/12), respiratory failure (3/12), atopic constitution (2/12), diarrhea (2/12), dysphagia (1/12), hypothermia (1/12), wheezing (1/12), hypertension (1/12), liver failure (1/12) and metabolic alkalosis (1/12). Conclusions:NS is caused by SPINK5 gene mutation with atypical manifestations in neonates. Neonates with diffuse erythema and desquamation of the skin, repeated infections, dry hair and especially with high blood IgE should be considered the possibility of NS. Genetic testing is conducive to early diagnosis, guiding treatment decisions and providing a basis for genetic counseling.