Case Report: Progressive Asymmetric Parkinsonism Secondary to CADASIL Without Dementia

Parkinsonism is a rare phenotype of cerebral autosomal dominant arteriopathy with subcortical infarction and leukoencephalopathy (CADASIL), all of which involve cognitive decline. Normal cognition has not been reported in previous disease studies. Here we report the case of a 60-year-old female patient with a 2-year history of progressive asymmetric parkinsonism. On examination, she showed severe parkinsonism featuring bradykinesia and axial and limb rigidity with preserved cognition. Magnetic resonance imaging (MRI) revealed white matter hyperintensity in the external capsule and periventricular region. Dopaminergic response was limited. A missense mutation c.1630C>T (p.R544C) on the NOTCH3 gene was identified on whole-exome sequencing, which confirmed the diagnosis of vascular parkinsonism secondary to CADASIL. A diagnosis of CADASIL should be considered in asymmetric parkinsonism without dementia. Characteristic MRI findings support the diagnosis.

Clinical observation of interstitial lung injury caused by the use of humidifier

Humidifier lung syndrome is a rare phenotype of hypersensitive pneumonitis (HP) caused by inhalation of fumes from contaminated climate appliances such as a humidifier and air conditioner. Since the described syndrome is rarely found in the Russian Federation, the practitioner should be wary of this pathology, carefully collect an anamnesis from the patient, and also carry out differential diagnostics with lung lesions of autoimmune, drug, infectious genesis. HP therapy includes exclusion of contact with the etiological factor and the appointment of systemic hormonal therapy.

Rare phenotype: Hand preaxial polydactyly associated with LRP6-related tooth agenesis in humans

Low-density lipoprotein receptor-related protein 6 (LRP6) is a pathogenic gene of selective tooth agenesis-7 (OMIM#616724). Although the malformation of the digits and fore- and hindlimbs has been reported in Lrp6-deficient mice, it has been rarely discovered in humans with LRP6 mutations. Here, we demonstrate an unreported autosomal dominant LRP6 heterozygous mutation (c.2840 T > C;p.Met947Thr) in a tooth agenesis family with hand polydactyly, and another unreported autosomal dominant LRP6 heterozygous mutation (c.1154 G > C;p.Arg385Pro) in a non-syndromic tooth agenesis family. Bioinformatic prediction demonstrated the deleterious effects of the mutations, and LRP6 structure changes suggested the corresponding functional impairments. Analysis on the pattern of LRP6-related tooth agenesis demonstrated the maxillary lateral incisor was the most affected. Our study report that LRP6 mutation might be associated with hand preaxial polydactyly in humans, which broaden the phenotypic spectrum of LRP6-related disorders, and provide valuable information on the characteristics of LRP6-related tooth agenesis.

A case of humidifier lung with a difficult differential diagnosis from COVID-19

ABSTRACT Acute respiratory illnesses that presented with diffuse ground-glass opacities (GGOs) on chest computed tomography (CT) scan suggest the diagnosis of coronavirus disease 2019 (COVID-19). However, many other diseases show similar CT findings, which often offer a difficult differential diagnosis. Here, we report a case of humidifier lung, a rare phenotype of hypersensitivity pneumonitis (HP), which mimicked COVID-19. A 71-year-old man was admitted because of dyspnea and diffuse GGOs found on chest CT scan. Although COVID-19 was initially suspected, his symptoms rapidly improved by the next day. A medical interview revealed that he had started using an ultrasonic humidifier 1 month ago. A high-resolution CT (HRCT) scan showed ill-defined centrilobular nodules and mosaic attenuation, which are typical of HP but atypical of COVID-19. The inhalation challenge test confirmed the diagnosis of humidifier lung. History-taking of humidifier use and a precise HRCT interpretation are helpful to differentiate it from COVID-19.

The Clinical and Genetic Characteristics of Chinese Male Pediatric Patients with Congenital Hypogonadotropic Hypogonadism

Purpose：Congenital hypogonadotropic hypogonadism (CHH) are invided into Kallmann Syndrome (KS) and normosmic HH(nHH). The clinical and genetic characteristics of CHH are more studied in adults, but less in pre-adults. Methods: Medical records of 126 patients with CHH at our hospital during 2008−2020 were evaluated. Results: Totally, seven patients (5.6%) had hypospadias. Among 49 patients with positive family history, delayed puberty, KS/nHH and olfactory abnormalities accounted for 44.9%, 16.3%, and 12.2%, respectively. Sixty-five patients completed the hCG prolongation test, and T levels of 24 patients were lower than 100 ng/dl. 25 CHH-related genes were found in 78 patients, digenic mutations in 23 patients, and trigenic mutations in 3 patients. The most common pathogenic genes were FGFR1 (21.1%), PROKR2 (17.9%), ANOS1 (12.6%) and CHD7 (12.6%). The oligogenicity rate of common autosomal dominant heredity genes accounted for 50.0% (FGFR1, 10/20) and 33.3% (CHD7, 4/12), of autosomal recessive heredity gene PROKR2 accounted for 47.1% (8/17). And W178S accounted for 58.8% of all mutations in PROKRR2.Conclusion: Micropenis and cryptorchidism are important cues for CHH in pre-adulthood; hypospadias is a rare phenotype of CHH. At least 22.9% of patients tested had testicular Leydig cell dysfunction (dual CHH). Oligogenic mutations were found in 27.4% of all patients with CHH. W178S in PROKRR2 maybe a founder mutation in Chinese CHH crowds.