Min Liu

To explore the candidate disease causing gene for a case with floppy infant syndrome (FIS). Single nucleotide polymorphism array (SNP array) was used for analyzing the whole genome copy number mutations in the proband. Multiple PCR combined with denaturing high performance liquid chromatography (DHPLC) was employed to verify the suspected mutations in the proband and his family members. A large duplication arr [hg19] Xq13.1: 67 987 646-73 805 828, which spans approximately 5.818182 Mb and encompasses 66 known genes, was identified in the proband. The multiple PCR-DHPLC assay confirmed duplication of HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1 and SLC16A2 genes in the proband. His mother and grandmother both had duplication of the above genes in one X chromosome, but his aunt had not. The large Xq13.1 duplication identified by the SNP array probably underlies the FIS in this family. For its high-throughput, high resolution and capacity of automation, SNP array has provided a first line method for the genetic testing for infants featuring developmental delay with unknown reason, mental retardation, autism, multiple malformation and FIS.

Objective: To identify candidate genes for the clinical diagnosis of floppy infant syndrome (FIS) using single nucleotide polymorphism (SNP) array in a specific FIS family. Methods: SNP array analysis of the whole chromosome copy number was performed in the proband (III₁). Multiple polymerase chain reaction (PCR) combined with denaturing high-performance liquid chromatography (DHPLC) was used to validate the array data. Results: A large 5.818182 Mb duplication (Xq13.1: 67987646-73805828), which encompasses 66 known genes, was found in III₁. The start and end points of the duplication were confirmed with an SNP array. Duplicated genes with potential roles in central and/or peripheral nervous system development (HDAC8, PHKA1, TAF1, DLG3, KIF4A, IGBP1, PJA1, and SLC16A2) were confirmed by multiple PCR-DHPLC in III₁. The patient’s mother and grandmother carry duplications in these eight genes, but only on one X chromosome, while the patient’s aunt does not carry any of the duplications. Conclusion: Based on the location of the eight candidate genes in Xq13.1, the large duplication found by SNP array does indeed exist and is predicted to be both novel and pathogenic. Moreover, we recommend SNP array as the first option for genetic diagnosis of both large-scale and rare/complicated diseases, such as FIS.

Rationale:Guillain-Barre Syndrome (GBS) as a paraneoplastic manifestation of small cell lung cancer has been published several times, while paraneoplastic GBS accompanied by pulmonary adenocarcinoma is rare.Patient concerns:An 80-year-old male was hospitalized with a 2-week history of fever and 10-day history of progressive ascending muscle weakness in the legs and arms. The patient felt weakness in legs at first when he was still able to move around, but the symptoms gradually progressed to the arms. At the time of office visit, he could no longer walk or hold up objects, and had absent deep-tendon reflexes as well as weakened left lung breath sounds.Diagnoses:Confirmed by the Cerebrospinal fluid (CSF) and electromyography examination, the patient was originally admitted into our hospital for GBS. However, radiology and histological examination revealed pulmonary adenocarcinoma. He was relatively old and confirmed to have pulmonary adenocarcinoma with simultaneously detected GBS, so was considered to be a paraneoplastic syndrome, rather than pure GBS.Interventions:The patient was treated with methylprednisolone at 80 mg Qd for 10 consecutive days, which resulted in improvement in arms, then tapering to lower doses for 3 months.Outcomes:The patient showed temporary relief until relapse 6 months later, when the patient gave up treatment.Lessons:To our knowledge, this is the first case of pulmonary adenocarcinoma that was diagnosed based on Guillain-Barre-like syndrome, which is very difficult to diagnose and treat. We suggest that elderly patients with GBS should not be considered as simple GBS and should be thoroughly examined to exclude systemic diseases, especially paraneoplastic neurological syndromes. In addition, the elderly should be screened regularly for tumor markers.