Pulmonary acinar hypoplasia (PAH) and lacrimo-auriculo-dento-digital (LADD) syndrome have both been associated with loss-of-function variants in, or deletions of FGF10 . Here we report a multi-generational family with seven members manifesting varying features of LADD syndrome, with one individual dying in early infancy of PAH. Whole genome sequencing in one family member identified a 12,158 bp deletion on chromosome 5p12 that removes two of the three exons of FGF10 . Allele-specific PCR demonstrated that all affected family members, including the individual with PAH, carried the 12 kb deletion. We conclude the deletion is pathogenic and expands the mutational spectrum of FGF10 variants in LADD syndrome. The common mechanism underlying the variable clinical features of LADD syndrome is defective terminal branching of salivary and lacrimal glands and pulmonary acini, regulated by the TBX4-FGF10-FGFR2 pathway. The variable phenotypic expressivity of FGF10 haploinsufficiency from relatively benign to lethal is likely due to variation at other genetic loci.

Germline pathogenic variants in AMER1 cause osteopathia striata with cranial sclerosis (OSCS: OMIM 300373), an X-linked sclerosing bone disorder. Female heterozygotes exhibit metaphyseal striations in long bones, macrocephaly, cleft palate, and, occasionally, learning disability. Male hemizygotes typically manifest the condition as fetal or neonatal death. Somatically acquired variants in AMER1 are found in neoplastic tissue in 15-30% of patients with Wilms tumor; however, to date, only one individual with OSCS has been reported with a Wilms tumor. Here we present four cases of Wilms tumor in unrelated individuals with OSCS, including the single previously published case. We also report the first case of bilateral Wilms tumor in a patient with OSCS. Tumor tissue analysis showed no clear pattern of histological subtypes. In Beckwith-Wiedemann syndrome, which has a known predisposition to Wilms tumor development, clinical protocols have been developed for tumor surveillance. In the absence of further evidence, we propose a similar protocol for patients with OSCS to be instituted as an initial precautionary approach to tumor surveillance. Further evidence is needed to refine this protocol and to evaluate the possibility of development of other neoplasms later in life, in patients with OSCS.

Osteopathia striata with cranial sclerosis (OSCS) is an X-linked dominant condition characterised by metaphyseal striations, macrocephaly, cleft palate, and developmental delay in affected females. Males have a more severe phenotype with multi-organ malformations, and rarely survive. To date, only frameshift and nonsense variants in exon 2, the single coding exon of AMER1, or whole gene deletions have been reported to cause OSCS. In this study, we describe two families with phenotypic features typical of OSCS. Exome sequencing and multiplex ligation-dependent probe amplification (MLPA) did not identify pathogenic variants in AMER1. Therefore, genome sequencing was employed which identified two deletions containing the non-coding exon 1 of AMER1 in the families. These families highlight the importance of considering variants or deletions of upstream non-coding exons in conditions such as OSCS, noting that often such exons are not captured on probe or enrichment-based platforms because of their high G/C content.

Rationale:Necrotizing fasciitis (NF), characterized by widespread fascial necrosis, is a rare disease in clinic. Fournier gangrene (FG) is a special type of NF involved of perineum and scrotum. To our knowledge, no article has reported on bilateral femoral posterior neurocutaneous perforater flap treating for FG.Patient concerns:A 61-year-old Chinese male complained of perineal skin necrosis for 19 days. The patient received treatment in other hospital due to chronic bronchitis on April 15th and body temperature ranged from 38 to 39 °C. Then he received antiinfection therapy. Perianal cutaneous occurred mild necrosis on May 08th. And the necrosis generally deteriorated. He came to our hospital for treating necrosis in area of perineum and scrotum on May 28th.Diagnoses:He was diagnosed with FG and chronic bronchitis.Interventions:The patient underwent debridement on June 2nd and received bilateral femoral posterior neurocutaneous perforater flap on June 29th. Besides, the patient was treated with whole-body nutrition support and antibiotic treatment.Outcomes:One week after the 2nd operation, the flap showed normal color. The result shows good outcome and no recurrence of the clinical symptoms occur till now.Lessons:FG is rare. Bilateral femoral posterior neurocutaneous perforater flap is an effective procedure to treat FG. The outcome of combined therapy is satisfactory.

Introduction:Whitlow is a common disease in clinic, characterized by pain and swelling of finger. However, few articles had reported on extensive infection in the forearm caused by whitlow infected by mycobacterium tuberculosis (MTB).Patient concerns:A 70-year-old Chinese female complained of fester in back of left hand for 5 days. She had a history of recurrent whitlow for 14 months and pulmonary tuberculosis (TB). She received treatment in another hospital due to whitlow on July 2016. Then she was treated with incision and drainage. However, whitlow presented again several times before coming to our hospital. She came to our hospital on September 7, 2017 and x-ray of forearm showed that radius, ulna, and carpal were eroded.Diagnoses:She was diagnosed with left extensive infection in the forearm caused by whitlow infection by MTB.Interventions:Considering her serious and extensive condition, we performed left forearm amputation on September 12, 2017. We collected some soft tissue cut down during surgery and conducted pathological examination. Finally, pathological result showed MTB infection. Then that patient was treated with antituberculosis therapy.Outcomes:Up to now, illness condition has not progressed. A recent x-ray of forearm showed no osteolysis in humerus.Conclusions:Extensive infection in the forearm after recurrent whitlow infection by MTB is rare. So when we face recurrent whitlow, a rapid diagnosis and treatment are required to prevent complications. This case reminds us that recurrent whitlow is dangerous. Attention must be paid to recurrent whitlow. If necessary, amputation should be considered.