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Russell-Silver syndrome (SRS) is a rare condition characterized by poor growth before and after birth along with multiple physical and psychosocial characteristics such as short stature, characteristic facial features, body asymmetry, feeding difficulties, and learning disabilities. In this study, we report a family with 2 recurrent SRS pregnancies due to a derivative chromosome 15 that is the result of a maternally derived t(11;15) translocation, detected by non-invasive prenatal testing (NIPT). The 2 SRS fetuses were diagnosed by chromosomal microarray analysis, but a balanced, reciprocal translocation of the mother was disclosed by the combination of routine karyotyping and FISH. This study demonstrates that NIPT has the ability to identify submicroscopic copy number variations (CNVs) in fetuses, which in some cases may result from a parent being a balanced rearrangement carrier. Because of the differences in resolution and the various benefits and limitations of each genetic technique, great care must be taken when deciding on which test(s) to employ in family studies.

Introduction: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory central nervous system disorder that preferentially affects the optic nerve and the spinal cord. Although NMOSD is more commonly an idiopathic autoimmune condition associated with antibodies against aquaporin-4 (AQP4)-IgG, the disease may also occur as a paraneoplastic syndrome in rare instances. In these cases, the expression of AQP4 by the tumor is likely the trigger of the autoimmune response. Case Presentation: We describe the case of a 32-year-old woman who presented with progressive tetraparesis, cranial involvement, respiratory failure, and spinal cord MRI compatible with longitudinally extensive transverse myelitis, few days after being diagnosed with a T3N1M0 triple-negative right breast cancer. Due to the history of concurrent breast cancer and after ruling out metastatic spinal cord involvement, the possibility of a paraneoplastic origin was raised. AQP4-IgG were found in the serum and CSF by cell-based assay, confirming the diagnosis of NMOSD. The patient was treated with corticosteroids, plasma exchange, and rituximab. Concomitantly, breast cancer therapy was started with an adapted neoadjuvant chemotherapy scheme based on carboplatin and paclitaxel. An initial slight improvement slowed down; so, a right mastectomy with lymphadenectomy was performed. Expression of AQP4 was demonstrated in the tumor. The patient presented a significant neurological improvement after combined treatment regaining muscular balance and strength in upper and lower extremities. Conclusion: NMOSD may have a paraneoplastic origin associated with breast cancer and the importance of its early detection since the combination of tumoral and immunosuppressive therapy may improve the patient’s prognosis.

Introduction: Lupus erythematosus (LE) is a chronic autoimmune disease that frequently causes hair loss and scalp lesions. Hair loss can be scarring and nonscarring, diffuse, or patchy. The nonscarring patchy alopecia is usually related to systemic LE (SLE) and may simulate alopecia areata (AA), reason why it is named areata-like lupus. Our case was diagnosed with areata-like lupus but did not meet criteria for SLE. Case Report: A 63-year-old woman presented with irregular nonscarring patchy alopecia in the temporal and frontoparietal scalp. Trichoscopy showed exclamation mark hairs, vellus hairs, and sparse yellow dots. Histology revealed epidermal vacuolar interface dermatitis, lymphohistiocytic infiltrate around the bulbs of anagen follicles, and eccrine glands. Direct immunofluorescence showed deposits of C3, IgA, and IgG in the basement membrane zone. Discussion: Patients with cutaneous LE can also manifest as nonscarring patchy alopecia that is clinically similar to AA, despite the absence of systemic manifestations. Areata-like lupus is secondary to the lupus autoimmune infiltrate that affects the skin including the hair follicles. Trichoscopy, histology, and direct immunofluorescence are important to differentiate this form of alopecia from AA, which is believed to have a higher incidence in lupus patients.

Introduction: Vein of Galen malformation (VGM) results from an aneurysmal aberration with an arteriovenous shunting of blood and is the most frequent arteriovenous malformation in infants and fetuses. The congenital malformation develops during weeks 6–11 of fetal development. Infants often die from high-output congestive heart failure. VGM is mostly considered as a sporadic condition with minimal recurrence risk in subsequent pregnancies. Mendelian forms of VGM have rarely been described as infrequent phenotypic presentations of 2 disorders: capillary malformation-arteriovenous malformation syndrome (RASA1, EPHB4) and hereditary hemorrhagic telangiectasia (ENG, ACVRL1, and SMAD4), both showing autosomal dominant inheritance. Case Presentation: Here, we report on a consanguineous couple with recurrent VGM in 2 pregnancies. Both partners were found to be affected by hereditary hemorrhagic telangiectasia due to a known pathogenic heterozygous c.790G>A (p.Asp264Asn) variant in ENG. Fetal DNA was unavailable, however in view of the mild phenotype in the couple, along with the severe prenatal presentation in 2 pregnancies, the fetus was presumed to be homozygous for the ENG variant. A subsequent pregnancy revealed a fetus heterozygous for the variant, which had an uneventful perinatal course. Conclusion: This report highlights a severe perinatal lethal phenotype due to biallelic variants in a gene hitherto known to cause an autosomal dominant disorder.

Introduction: Mendelian disorders of the epigenetic machinery are a growing group of disorders exhibiting several overlapping clinical features that are probably due to common abnormalities at the epigenomic level, which lead to downstream convergence at the transcriptomic level. Case presentation: Here, we report a new case of short stature, brachydactyly, intellectual developmental disability, and seizures (SBIDDS) syndrome with a severe ocular phenotype and hypogonadism. Conclusion: Similarities and connections with other mendelian disorders of the epigenetic machinery are highlighted, confirming SBIDDS′ enrolment as a new spoke of the epigenetic machinery wheel.

Introduction: Hypotonia-cystinuria syndrome is a contiguous gene deletion syndrome that is characterized by hypotonia, developmental delay, and cystinuria type A. We present a male patient who was admitted to our center with clinical findings of hypotonia-cystinuria syndrome and diagnosed with megaconial congenital muscular dystrophy and cystinuria. Case Presentation: A 16-month-old male patient was admitted with complaints of restlessness and body laxity. It was stated that the patient had hypotonia and growth retardation at the age of 2 months. Physical examination revealed mild hypotonia, growth retardation, and development delay, while laboratory examinations identified elevated serum creatine kinase and elevated dibasic amino acid in urine analysis. Because of the findings of hypotonia, growth retardation, developmental delay, and cystinuria, hypotonia-cystinuria syndrome was considered as a differential diagnosis. However, by chromosomal microarray no contiguous deletion in region 2p21 was found, while a novel homozygous c.225-2A>T pathogenic variant in the CHKB gene and a c.1266_1267delGT heterozygous variant in the SLC7A9 gene inherited from the mother were identified with whole-exome sequencing. The co-occurrence of megaconial congenital muscular dystrophy and cystinuria, mimicking hypotonia-cystinuria syndrome, was confirmed. Conclusion: This case suggests that in countries with a high frequency of consanguineous marriage, even if the molecular genetic analysis results are not compatible with the clinical findings, it should be kept in mind that different genetic diseases may coexist.

Introduction: Spitz nevus is an uncommon, benign melanocytic proliferation that primarily appears on face, trunk or lower extremities of children. This lesion may share clinical and microscopical characteristics with melanoma, making it a diagnostic and management challenge. Case Report: A 13-year old male presented with an asymptomatic chronic dermatosis located on the third left-hand nail. Cutaneous examination revealed a homogeneous dark brown melanonychia which extended up to the cuticle. Upon dermoscopy, longitudinal bands measuring less than 3 mm wide of heterogeneous colors ranging from light to dark brown, and positive Hutchinson’s sign were observed. Discussion/Conclusion: We report the second case of a Spitz nevus ungually localized which strongly resembled an ungual melanoma with a positive Hutchinson’s sign upon dermoscopy. Describing the infrequent presentation and location of the Spitz nevus poses an opportunity to establish diagnostic and management criteria in the near future.

Tyrosinemia type III is an extremely rare autosomal recessive disease, with only 19 patients yet reported. It is caused by a deficiency of the 4-hydroxyphenylpyruvate dioxygenase enzyme, resulting from biallelic mutations in the HPD gene. Although the clinical spectrum of the disease is not fully known, most patients present with neurodevelopmental symptoms. We report on a 20-month-old patient who was investigated due to developmental delay and dysmorphic features. The girl had a novel splice-site mutation in the HPD gene and ventriculomegaly in cranial imaging, which was not previously associated with tyrosinemia type III. Our patient had mild subjective improvement in social skills and language development after dietary therapy was started and her tyrosine levels decreased. We also summarize clinical, biochemical, and genetic findings of previously published patients with biallelic HPD mutations.

Introduction: Recent studies have demonstrated a correlation between pemphigus and hidradenitis suppurativa (HS). Case Presentation: Here, we report the case of a 58-year-old man affected by HS for about 30 years who was found to have lesions attributable to pemphigus during a checkup. Discussion/Conclusion: There are few data in the literature on the use of systemic corticosteroids for the two diseases, and our article wants to be a food for thought on the management and treatment of these diseases.

Pelger-Huet anomaly (PHA) is a benign hematological anomaly that is characterized by impaired lobulation of neutrophils with a coarse nuclear chromatin. Skeletal abnormalities may accompany this anomaly. Autosomal recessive deafness-4 (DFNB4) with enlarged vestibular aqueduct (EVA) comprises a phenotypic spectrum of sensorineural hearing loss (SNHL). We report a case with SNHL, multiple skeletal anomalies including osteochondroma, developmental delay, and PHA. Molecular studies revealed a heterozygous pathogenic variant in the LBR gene and a homozygous likely pathogenic variant in the SLC26A4 gene. Due to these 2 variants, he was diagnosed with PHA and DFNB4 with EVA. If goiter develops, DFNB4 with EVA is named Pendred syndrome (PDS), so the patient will be followed up for this condition, and in the current literature, there is no case with PDS and PHA co-existence either. PHA may be accompanied by multiple skeletal abnormalities. In our case, there is also concomitance with osteochondroma. Although these are independent and distinct diagnoses, we present this case due to the concomitance of these situations.

Introduction: Classic galactosemia is a disorder of the galactose metabolism and is inherited as an autosomal recessive disease. It is caused by a complete or severe deficiency of galactose-1-phosphate uridyltransferase (GALT), and in rare cases, atypical galactosemia can manifest at older ages. Wilson disease (WD) is a disorder of the copper metabolism that, like galactosemia, is inherited as an autosomal recessive disease. Hepatic, neurological, or psychiatric symptoms can be seen, independently or in combination, and symptoms vary from family to family. We present here a patient diagnosed with both WD and galactosemia. Case Presentation: A 6-year-old girl was referred to our center with elevated transaminase levels and hepatosplenomegaly. The child, birthweight of 2,200 g, was born to first-degree consanguineous parents after a full-term uneventful pregnancy and was hospitalized in the neonatal period due to indirect hyperbilirubinemia, gastrointestinal bleeding, diarrhea lasting 2 weeks, and elevated liver enzymes. Hepatosplenomegaly was evident at the time of admission, a cataract was detected, and a neuropsychiatric evaluation revealed borderline mental capacity, as well as cognitive and speech retardation. Metabolic investigations revealed no specific findings other than trace positivity of reducing substances in the urine. A liver biopsy revealed copper accumulation in hepatocytes and low ceruloplasmin levels. Although WD was suspected in the patient, this diagnosis did not explain the intellectual disability, behavioral disorder, or cataract findings. A genetic analysis revealed homozygous mutations in the ATP7B and GALT genes. The galactose-1-phosphate uridyltransferase enzyme level was found to be low, and the patient was diagnosed with coexisting WD and galactosemia. Conclusion: Coexistences of rare genetically transmitted diseases can be seen in countries where consanguineous marriages are common (Saudi Arabia, Iran, Pakistan, etc.), as in our country, Turkey.

Introduction: Although adalimumab is the only approved biologic for the treatment of hidradenitis suppurativa (HS), the treatment response may not be satisfactory in all patients. Recently, many other biological agents, including interleukin 17 inhibitors such as ixekizumab, have shown promise. Case Presentations: Five severe HS (Hurley stage III) patients resistant to conventional treatments and adalimumab for at least 3 months were recruited. Patients were prescribed ixekizumab with a scheme approved for psoriasis (160 mg once, followed by 80 mg at weeks 2, 4, 6, 8, 10, and 12.) The primary outcome measure was achieving the Hidradenitis Suppurativa Clinical Response (HiSCR) score following 12 weeks. Secondary outcome measures included the patient-reported Dermatology Life Quality Index (DLQI) and visual analog scale (VAS). Four of 5 patients (80%) achieved HiSCR. While improvement was observed in the VAS and DLQI scores of 4 patients, the decline was limited in 1 patient. No adverse event was recorded related to ixekizumab. Conclusion: The result of our observation suggests that ixekizumab may be effective for HS, especially in challenging cases.

Introduction: Lipedematous scalp (LS) is a rare condition characterized by thickened adipose tissue in the subcutaneous layer of the scalp resulting in a soft, spongy, or thick consistency of the scalp. When associated with hair loss, this condition is called lipedematous alopecia (LA). Various imaging modalities have been used to diagnose LS and LA along with histopathology. Case Presentation: We present 2 cases of LS: a 56-year-old female with a 1-year history of hair thinning, pain, and tenderness at the vertex scalp and a 60-year-old female with a 5-year history of lichen planopilaris presenting with a 1-year history of itching and soreness on the crown of her head. Ultrasound (US) was used for diagnosis, treatment response surveillance, routine clinical examination, and symptom assessment. Follow-up US revealed no improvement in scalp thickness in either case despite symptom improvement and visual improvement in hair growth. Discussion/Conclusion: US has been reported as a helpful tool in the diagnosis of LS; however, treatment response was better approximated by hair growth and symptom alleviation. We found that once the diagnosis with made with US, clinical monitoring is adequate as symptom improvement and hair growth may not correlate with a change in scalp thickness.

Background: The B-Raf proto-oncogene (BRAFV600E) gene mutation has been identified in a variety of malignancies, but no evidence of the efficacy of vemurafenib treatment in BRAFV600E mutant breast cancer (BC) has been reported. Case Presentation: We reported a 60-year-old woman with confirmed triple-negative BC with BRAFV600E mutation. Progression-free survival (PFS) for first-line chemotherapy was 7 months. The patient received vemurafenib and albumin-bound paclitaxel as second-line therapy, exhibiting regression of some pulmonary metastatic lesions with concomitant progression of other lesions, and achieved 4.4 months of PFS. Genetic testing of the progressed pulmonary lesion revealed the BRAFV600E mutation, and acquired new mutations and AR amplification. The patient ultimately died of multiple organ failure and achieved 12 months of overall survival. Conclusions: The BRAFV600E mutation may be a potential prognostic factor and therapeutic target for BC.

Introduction: A wide spectrum of cardiovascular (CV) toxicity is associated with anticancer treatment, and nearly all chemotherapeutic agents can elicit CV toxicity. Inhibitors of cyclin-dependent kinases 4/6 (CDK4/6Is) have become standard of care in the treatment of hormone receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer (MBC). CV side effects are uncommon with CDK4/6Is and only include QT prolongation, with a low incidence rate. Case Presentation: This paper describes 2 cases of new-onset second-degree type 2 atrioventricular (AV) blocks requiring permanent cardiac pacing involving 2 women with MBC receiving ribociclib or abemaciclib. Both our patients had no known history or risk factors of cardiac disease and a normal 12-lead resting electrocardiogram (ECG) when diagnosed with breast adenocarcinoma. Both patients have been subjected to surveillance for cardiotoxicity with serial ECG and echocardiography. No left ventricular dysfunction or arrhythmia was found during the follow-up, and cardiac biomarkers were normal. Conclusion: To our knowledge, these are the first cases reported in the literature of new-onset advanced AV blocks in patients under treatment with CDK4/6Is, suggesting the clinical relevance of a more frequent ECG monitoring, besides the QT interval, in these patients.

Introduction: Feingold syndrome type 2 (FGLDS2) is an ultra-rare genetic disorder characterized by short stature, microcephaly, digital abnormalities, and intellectual disability. Until now, 22 patients have been reported in the literature. FGLDS2 is caused by a germline heterozygous deletion of 13q resulting in haploinsufficiency of the MIR17HG gene. Case report: In the present study, we evaluated clinical, radiological, and genetic analyses of a 10-year-old Turkish-origin girl with short stature, brachydactyly, intellectual disability, hematuria, and proteinuria. Conclusion/Discussion: In the array-CGH analysis, a 15.7-Mb deletion, arr[hg19] 13q22q31.3(78,241,132_93,967,288)×1, was detected, and this alteration was evaluated to be pathogenic. The deletion of this region covering the MIR17HG gene is a potential cause of FGLDS2. Also, at her clinical exome sequencing study, a heterozygous c.2023G>A p.(Gly675Ser) variation was detected in the COL4A5 gene (NM_000495.4) that was likely pathogenic in up-to-date databases. As a result, we report on a patient who has FGLDS2 and Alport syndrome. This is the first report of a Turkish-origin FGLDS2 patient. Reporting new cases expands the range of phenotypes, plays a crucial role in understanding the FGLDS2 pathogenesis, and is important in terms of screening at-risk family members for giving appropriate genetic counseling and preimplantation genetic diagnosis opportunities.

Mevalonate kinase deficiency (MKD) is a periodic fever syndrome. Nonsteroidal anti-inflammatory drugs, corticosteroids, and anakinra are the most common treatments. However, colchicine is considered insufficient in disease control. In this case report, we present an 8-month-old infant with an atypical presentation of MKD. She had recurrent fever episodes, diarrhea, and lethargy. Elevated mevalonic acid was not detected in the urine. However, the genetic investigation showed a novel pathogenic heterozygous c.925G>C (p.Gly309Arg) variant and a heterozygous c.1129G>A (p.Val377Ile) mutation in the MVK gene. The patient was treated with colchicine for 8 months. During treatment, no further fever episode had been observed. It should be kept in mind that mevalonic acid excretion may not be present in the urine with mild MKD. Colchicine may be a reasonable option in mild MKD patients for a longer duration of treatment due to favorable adverse event profiles.

Okur-Chung neurodevelopmental syndrome is a rare autosomal dominant disorder caused by pathogenic variants in CSNK2A1, which encodes the alpha 1 catalytic subunit of ­casein kinase II. This syndrome is characterized by intellectual disability, developmental delay, and multisystemic ­abnormalities including those of the brain, extremities, and skin as well as cardiovascular, gastrointestinal, and immune systems. In this study, we describe a 5-year-old boy with a de novo novel nonsense variant in CSNK2A1, NM_001895.3:c.319C>T (p.Arg107*). He showed bilateral persistent hyperplastic primary vitreous with microphthalmia, lens dysplasia, and coloboma. Ocular manifestations are very rare in this syndrome, and this study expands the spectrum of the clinical presentations of this syndrome.

Introduction: Acrodermatitis continua of Hallopeau (ACH) is a rare, chronic, and recurrent form of pustular psoriasis (PP) localized to one or more digits. Due to the rarity of ACH, no clear treatment guidelines are currently available, making the therapeutic approach more complex. Case Presentation: We report the first case of a young woman with ACH who was successfully treated with certolizumab pegol (CZP). Discussion/Conclusion: PP and ACH are difficult to treat, and biologics may be an option more manageable than cyclosporine. CZP is the safest biologic therapy during pregnancy, so there is low risk in prescribing it in women with childbearing potential. However, continuing biological therapy during pregnancy always involves an assessment of the clinical benefits, which must outweigh the risks.

Eccrine porocarcinomas (EPCs) are rare tumours, albeit the most common malignant adnexal tumours of the skin. They can present with very heterogeneous clinical and dermoscopic features, rendering diagnosis limited to histopathological examination alone. We share 2 cases of EPCs, one of which arose in a patient with a prior diagnosis of cutaneous squamous cell carcinoma (SCC) and another whose EPC was likely a malignant transformation of an existing poroma. An occurrence of porocarcinoma after the diagnosis of SCC may suggest the possibility of unknown risk factors for both. Positivity to androgen, oestrogen, and epidermal growth factor receptors was seen in a proportion of porocarcinomas, and this may prompt further research on combination therapy between conventional treatment modalities with hormone receptor antagonists. Malignant change of a poroma may be a more common phenomenon than we would expect based on the current literature.

White piedra is a superficial fungal infection of hair caused by Trichosporon species. It presents clinically as white nodules encasing the hair shafts and may lead to increased fragility. It can usually be differentiated easily from clinically similar conditions based on clinical and microbiologic features. We report a case of white piedra of scalp hair in a 32-year-old female caused by T. ovoides, diagnosed using clinical, trichoscopic, microbiologic and molecular methods. In this case, trichoscopy acted as an interface between clinical and microbiologic examination, obviating the need for hair shaft microscopy. The genus Trichosporon contains 6 species of clinical significance viz., T. asahii, T. asteroides, T. cutaneum, T. inkin, T. mucoides, and T. ovoides, which cannot be differentiated based on their morphologic characteristics. A genotypic identification using molecular methods helped determine the causative species. It was treated successfully with oral itraconazole and topical ketoconazole.

Alopecia areata (AA), an autoimmune disease with a relapsing-remitting course, represents the second cause of non­scarring alopecia worldwide and is associated with several comorbidities, notably atopic dermatitis (AD). In particular, AD is related to its more severe forms alopecia totalis (AT) and alopecia universalis (AU) [Nat Rev Dis Primers. 2017;3:17011]. Considering that AA has been classified as T helper 1-driven disease, whereas AD is the prototypical T helper 2 (Th2)-driven skin disorder, recent studies suggest that these forms may underlie a different chemokine expression resulting in a Th2 skewing as a key pathomechanism that could explain this association [JAMA Dermatol. 2015 May;151(5):522–8]. Several reports showed that dupilumab, a fully human monoclonal antibody targeting the interleukin 4α receptor and thus downregulating Th2 response, led to an improvement of AA associated with AD; most of these patients were females with AT or AU, early-onset AD, and atopic comorbidities [Exp Dermatol. 2020 Aug;29(8):726–32]. We report here a case to further support this hypothesis.

Canities subita has been considered by some authors an acute episode of diffuse alopecia areata in which the sudden whitening is caused by the preferential loss of pigmented hair in this immune-mediated disorder. Clinically, the “salt and pepper” pattern of hair color is the most frequent manifestation of canities subita. However, the exact physiopathology of canities subita is not completely understood. A 69-year-old Caucasian man was referred for the sudden and asymptomatic whitening of the hair on the scalp and eyebrows, without an associated hair loss. The trigger was the death of his brother. Hair whitening appeared 24 h after the event. He reported a history of alopecia areata in plaques on the scalp, with spontaneous complete resolution in 2006. The physical examination showed full whitening hair on the scalp and eyebrows. Eyelashes were not affected. The pull test was negative, and the patient denied a significant hair loss in the last days. The histopathological study showed several follicle-sebaceous structures in the anagen, and one of them (inset) with a transforming hair bulb. The anterior bulb was surrounded by a lymphocytic inflammatory infiltrate in an advanced stage of transformation to the catagen and incipient scar changes. Immunohistochemistry staining showed a positive anti-PD-L1 antibody expressed in the inflammatory infiltrate. Based on the clinical and histological findings, a diagnosis of canities subita was made. The histopathological study showed a positive staining for anti-PD-L1 antibodies, supporting the role of the immune system in the development of this phenomenon. The interaction between melanogenesis and the lymphocytes warrants further research.

Background: Much remains unknown about the transmission of the SARS-CoV-2 virus. Pregnant women are considered part of the risk population, and vertical transmission of other coronaviruses has been suggested; however, this type of transmission in SARS-CoV-2 is believed to be unlikely. Case Report: A newborn delivered in term via cesarean section to an asymptomatic but COVID-19-positive 35-year-old woman started with respiratory distress in the first 30 min of life. A chest radiograph revealed pneumothorax and ground glass opacities. Ventilatory support with continuous positive airway pressure was needed. Given the respiratory failure and the positive test from the mother, the patient was sampled for SARS-CoV-2 (RT-PCR) at minute 30 of life, with a positive result reported at 36 h of life. No complications had been present during pregnancy, and cardiac screening and blood cultures revealed no other etiologies. Conclusion: Vertical transmission was highly likely in this case. Clinicians should be alert and report similar cases.

The radiological findings of COVID-19 are well-described, including its evolution. In an earlier report of admission chest radiographs of patients with COVID-19, we anecdotally noted relative sparing of the left upper zone (LUZ). We subsequently aimed to describe the main chest radiograph findings in another cohort, focusing on zonal predominance. The admission chest radiographs of 111 patients with CO­VID-19 pneumonia requiring intensive care admission were reviewed by 2 thoracic radiologists and categorized according to the predominant pattern into either ground-glass opacities (GGOs), alveolar infiltrates and/or consolidation, or reticular and/or nodular infiltrates or an equal combination of both, and the extent of disease involvement of each of the zones using a modified Radiologic Assessment of Lung Edema (RALE) score. Parenchymal changes were detected in all. In total, 106 radiographs showed GGOs, alveolar infiltrates, and/or consolidation, and 5 had a combination of reticular/nodular infiltrates as well as GGOs, alveolar infiltrates, and/or consolidation. The LUZ had a significant lower grading score than the right upper zone: 1 versus 2 (p < 0.001). Likewise, the upper zones had a significant lower score than the mid and lower zones (p < 0.001). Our findings confirmed the relative sparing of the LUZ in severe COVID-19 pneumonia.

Introduction: 3M syndrome is an autosomal recessive disorder characterized by characteristic facial features, severe pre- and postnatal growth restriction (CUL7), obscurin-like 1 (OBSL1), and coiled coil domain containing protein 8 (CCDC8). Case presentation: Here, we report a patient who was referred to our clinic due to short stature and developmental delay. Physical examination revealed prenatal onset short stature, low birth weight, and normal head circumference. She displayed several dysmorphic facial features in addition to developmental delay and bilateral sensorineural hearing loss. The physical findings were suggestive of 3M syndrome. Genetic assessment revealed a novel homozygous frameshift c.418_419delAC (p.Thr140Cysfs*11) variant in the CUL7 gene and a previously reported pathogenic nonsense homozygous c.942C>A (p.Cys314Ter) variant in the ILDR1 gene. The parents were heterozygous for the same variant. Discussion: 3M syndrome should be considered in the differential diagnosis of patients with short stature and typical facial features even if in the presence of other inconsistent features such as developmental delay. In addition, it is important to take into account the co-occurrence of rare autosomal recessive genetic disorders especially in countries with a high consanguineous marriage rate.

Introduction: Cri-du-chat syndrome is generally diagnosed when patients present a high-pitched cry at birth, microcephaly, ocular hypertelorism, and prominent nasal bridge. The karyotype is useful to confirm deletions in the short arm of chromosome 5 (5p–) greater than 10 Mb. In cases of smaller deletions, it is necessary to resort to other molecular techniques such as fluorescence in situ hybridization, multiplex ligation-dependent probe amplification (MLPA) or genomic array. Case Presentation: We report a family with an atypical deletion in 5p (mother and 2 children) and variable phenotypes compared with the literature. We applied a P064 MLPA kit to evaluate 5p– in the mother and the 2 children, and we used the Infinium CytoSNP-850K BeadChip genomic array to evaluate the siblings, an 11-year-old boy and a 13-year-old girl, to better define the 5p breakpoints. Both children presented a high-pitched cry at birth, but they did not present any of the typical physical features of 5p– syndrome. The MLPA technique with 5 probes for the 5p region revealed that the patients and their mother presented an atypical deletion with only 4 probes deleted (TERT_ex2, TERT_ex13, CLPTM1L, and IRX4). The genomic array performed in the siblings’ samples revealed a 6.2-Mb terminal deletion in 5p15.33p15.32, which was likely inherited from their mother, who presented similar molecular features, seen in MLPA. Discussion: The sparing of the CTNND2 gene, which is associated with cerebral development, in both siblings may explain why these 2 patients had features such as better communication skills which most patients with larger 5p deletions usually do not present. In addition, both patients had smaller deletions than those found in patients with a typical 5p– phenotype. This report demonstrates the utility of genomic arrays as a diagnostic tool to better characterize atypical deletions in known syndromes such as 5p– syndrome, which will allow a better understanding of the genotype-phenotype correlations.

INTRODUCTION: Whole-exome sequencing (WES) is becoming widely available in prenatal diagnosis. However, as with most scientific methods, WES also has its limitations. The aim of the study was to report a fetal case of RNU4ATAC-opathy which was missed by prenatal WES. CASE PRESENTATION: A 28-year-old healthy primigravida was revealed by ultrasound at 20 + 3 weeks of gestation to have a fetus with ventriculomegaly (left 15.1 mm/right 11.9 mm), hypoplastic vermis, and mild growth retardation. Chromosomal microarray analysis and trio WES failed to detect a pathogenic copy number variation and sequence variant. A repeat ultrasound at 23 + 3 weeks showed worsened growth delay and hydrocephalus (left 20.3 mm/right 11.0 mm) with vermis hypoplasia and agenesis of corpus callosum. Further study with whole-genome sequencing (WGS) detected 2 missense mutations of the noncoding RNU4ATAC (NR_023343.1) gene, n.51G>A (rs188343279) and n.16G>A (rs750325275), in the fetus, which were inherited from the father and mother, respectively. DISCUSSION: Our study highlights the limitation of WES. WGS might be a clinical option for patients who have a structurally abnormal fetus tested negative by WES.

INTRODUCTION: Calcium/calmodulin-dependent serine protein kinase (CASK) gene mutations cause microcephaly with pontine and cerebellar hypoplasia (MICPCH) and X-linked intellectual disability. Congenital heart disease (CHD) is a rare complication reported in only 4 male patients with full loss-of-function mutations. Here, we report the first male patient with mosaicism of a truncating variant of CASK complicated by CHD. CASE PRESENTATION: The patient is a 6-year-old male with MICPCH, ventricular septal defect, and developmental delay. He achieved rolling over but can not speak meaningful words. We identified a somatic mosaic variant of CASK: c.[725=/G>A], p.(W242*) and high mosaic ratios of 90% and 84% for mutant alleles in peripheral blood lymphocytes and skin fibroblasts, respectively. His developmental delay was severe but milder than that of previously reported CHD patients. DISCUSSION: Truncating CASK variants may be associated with CHD, even in a mosaic state, and even a low normal allele ratio could lengthen survivorship.

We report the disparate clinical progression of a couple infected by SARS-CoV-2 based on their immune checkpoint (IC) levels and immune cell distribution in blood from admission to exitus in patient 1 and from admission to discharge and recovery in patient 2. A detailed clinical follow-up accompanied by a longitudinal analysis of immune phenotypes and IC levels is shown. The continuous increase in the soluble IC ligand galectin-9 (Gal-9) and the increment in T-cell immunoglobulin and mucin domain-containing 3 (TIM-3) protein in T cells in patient 1 suggests an activation of the Gal-9/TIM-3 axis and, subsequently, a potential cell exhaustion in this patient that did not occur in patient 2. Our data indicate that the Gal-9/TIM-3 axis could be a potential target in this clinical setting, along with a patent effector memory T-cell reduction.

Tinea capitis is a common fungal infection in children but is less frequently encountered in adults. Tinea capitis presenting as diffuse hair loss is a rare presentation. When patient presents with a diffuse hair loss, tinea capitis is not commonly thought of as differential diagnosis. Low clinical suspicion can lead to inappropriate empiric treatments that delay diagnosis. Trichoscopy in tinea capitis obviates the need for lengthy and invasive procedure or even KOH examinations in the absence of a side lab for diagnosing this common scalp disorder and also avoids misdiagnosis. Trichoscopy not only differentiates tinea capitis from female patterned hair loss but also aids in differentiating ectothrix from endothrix. Here, we present case reports of tinea capitis masquerading as female pattern hair loss with trichoscopy aiding in diagnosis of endothrix infection.

Peripapillary and circumpapillary retinal intraocular metastases are rare and present a treatment challenge for ophthalmologists because of the high risk of iatrogenic injury to the optic nerve. There are no clear guidelines on the management of these lesions, and many clinicians will initially observe for improvement of the metastases with systemic chemotherapy before considering local therapy with external beam radiation. Radiation to the optic disc carries a significant risk of injuring the optic nerve, leading to worsening of vision. Alternative treatment approaches are needed. We present a patient with large-cell neuroendocrine carcinoma with metastasis to the peripapillary retina who was treated with intravitreal topotecan and with intravitreal aflibercept. Serial fundus photos, ultrasound, and optical coherence tomography demonstrated a reduction in size of the lesion and a decrease in subretinal fluid with intravitreal topotecan and aflibercept. In addition, visual acuity was stabilized during treatment. Intravitreal chemotherapy for intraocular metastases in vision-sensitive areas such as the peripapillary retina may be a viable alternative for patients who seek to preserve their vision and maintain their quality of life.

Introduction: Extraneural/-cranial metastases (ENM) of primary central nervous system (CNS) tumors are rare and may be diagnostically challenging. We describe the cytomorphological and pertinent clinical features of ENM in a case series assessed by fine-needle aspiration (FNA). A search of the laboratory information systems of 2 tertiary care centers in Toronto (2000–2015) was performed. Cases with direct extracranial/-spinal extension of CNS neoplasms were excluded. Microscopic slides of FNA and surgical specimens were reviewed. Demographic and clinicopathological data were retrieved. Case Presentation: Six cases were identified with the original diagnoses of glioblastoma, glioblastoma with primitive neuroectodermal tumor-like components, anaplastic ependymoma, myxopapillary ependymoma, atypical meningioma, and hemangiopericytoma. Median patient age at first diagnosis was 44 years (range 22–56). The time interval between initial diagnosis and first metastatic disease manifestation was 3 months to 19 years. All FNA diagnoses were rendered correctly. In 4 cases, immunohistochemistry was used to support the diagnosis. All cases had prior surgical intervention at the primary tumor site. In 4 cases, the ENM location was the ipsilateral parotid or buccal area. Two primary tumors in midline location developed ENM in the scapular area. Discussion/Conclusion: ENM are a rare manifestation of a range of different primary CNS tumors and may involve the ipsilateral head and neck mimicking clinically a salivary gland neoplasm. FNA can rapidly discriminate ENM from other, potentially more indolent conditions. Awareness of the clinical history is paramount to avoid diagnostic confusion.

Introduction: Hidradenitis suppurativa (HS) is a potentially disabling chronic inflammatory disease. The intermammary location, not clearly specified in the usual phenotypic classifications, entails significant functional and cosmetic compromise. Case Presentation: Eleven cases of predominantly intermammary disease with multiple fistulization and disfiguring scarring were observed at our Department between January 2016 and March 2020. They were young (mean age = 22 years) obese or overweight women, in which the medical-surgical approach has led to variable results. Discussion/Conclusion: Intermammary HS possibly represents a unique phenotypic presentation, likely to be fistulizing and severe. We believe that anatomo-functional considerations, which can be paralleled to pilonidal sinus disease, contribute to its pathophysiology and striking appearance, and further emphasize the importance of multidisciplinary endeavor to reduce the morbidity associated with this seemingly overlooked location.

Intellectual disability (ID) is characterized by limited or insufficient development of mental abilities, including intellectual functioning impairments, such as learning and understanding cause-effect relationships. Some cases have ID as the only finding and are called isolated cases. Conversely, cases accompanied by facial dysmorphism, microcephaly, autism spectrum disorder, epilepsy, obesity, and congenital anomalies are called syndromic developmental delay (DD)/ID. Isolated and syndromic DD/ID cases show extreme genetic heterogeneity. Genetic etiology can be detected in approximately 40% of the cases, whereas chromosomal abnormalities are observed in 25%. Obesity is a multifactorial disease in which both genetic and environmental factors play important roles. The role of heredity in obesity has been reported to be between 40 and 70%. Array-based comparative genomic hybridization (array-CGH) can detect CNVs in the whole genome at a higher resolution than conventional cytogenetic methods. Array-CGH is currently recommended as the first-tier genetic test for ID cases worldwide. In the present study, we aimed to evaluate clinical, radiological, and genetic analyses of a 12-year and 4-month-old girl with microcephaly, ID, and obesity. In the array-CGH analysis, a 3.1-Mb deletion, arr[GRGh37] 10q23.31g23.33 (92745793_95937944)×1 was detected, and this alteration was evaluated to be pathogenic. We consider that haploinsufficiency of the candidate genes (GPR120, KIF11, EXOC6, CYP26A1, CYP26C1, and LGI1) in the deletion region may explain microcephaly, ID, obesity, seizures, and ophthalmological findings in our patient. The investigation of 10q23.31q23.33 microdeletion in cases with syndromic obesity may contribute to molecular genetic diagnosis.

Primary cardiac tumors are extremely rare. Obtaining a tissue diagnosis is difficult and commonly requires open-heart surgery with associated morbidity. Esophageal endoscopic ultrasound (EUS) and EUS with the EBUS scope (EUS-B) provide real-time sampling of centrally located lung tumors and mediastinal lymph nodes. They also provide an excellent view of the left atrium, since it is located adjacent to the esophagus. To date, left atrium tumor diagnostics by endosonography is poorly explored. We describe 2 exceptional diagnostic cases of left atrium tumors in which cardiac surgery was hazardous due to the clinical condition or previous surgical interventions. During EUS-B-guided fine-needle aspiration (FNA), the left atrial masses were successfully and safely sampled, revealing a Burkitt lymphoma and a synovial sarcoma. FNA including cell block analysis enabled specific tumor diagnosis and molecular subtyping. Our findings suggest that in selected cases, linear endosonography qualifies as a minimally invasive technique for intracardiac tumor diagnostics.

Perianal hyperhidrosis (HH) is a rare form of primary focal HH and may become a major problem for the patient with a significant psychosocial burden and negative impact on the quality of life. Botulinum toxin injections are widely used as a second-line treatment option for axillary, palmar, and plantar HH with a good safety profile. Herein, we pre­sent a case of primary perianal HH successfully treated with Botulinum toxin A at a dose higher than that previously reported in literature, with a longer response, a higher degree of satisfaction, and no adverse effects. Moreover, we review the main aspects of the perianal anatomy that are essential to carry out the technique correctly and make dermatologists achieve expertise with the procedure.

Individuals with 3p deletion show a great clinical variability. Apparently, a 1.5-Mb terminal deletion, including the CRBN and CNTN4 genes, is sufficient to cause this syndrome. Partial trisomy 13q is a rare chromosomal abnormality with a variable phenotypic expression, but in most cases, patients have a phenotype resembling complete trisomy 13. The aim of the present study is to describe a 9-month-old Mexican male patient with 3p deletion/13q duplication and a novel clinical finding. He presented with facial dysmorphism and multiple congenital alterations. Echocardiogram revealed cardiac insufficiency with hypertrophic cardiomyopathy and pulmonary hypertension, not previously reported. Karyotype from the patient and his father were 46,XY,add(3)(p26) and 46,XY,t(3;13), respectively. Microarray assay of the proband exhibited an approximately 2.6-Mb loss at terminal 3p26.3 and a 27.7-Mb gain of the long arm in terminal chromosome 13 at q31.1q34. A chromosomal imbalance with a partial trisomy 13q31.1q34 and monosomy 3p26.3 of paternal origin were detected. Microarray assay of both parents were normal. The proband has a cardiomyopathy not previously reported. These data enrich the spectrum of clinical manifestations in 3p deletion/3q duplication chromosomopathy.

Osteoma cutis (OC) or cutaneous ossification refers to uncommon bone formation in the skin. Primary OC develops without any predisposing factor or pre-existing lesion, whereas secondary OC sets out as a dystrophic ossification following traumatic, cicatricial, and neoplastic factors or other cutaneous inflammations. Herein, we report a rare case of long-standing progressive primary OC of the scalp resected in 3 sessions with no recurrence after 1 year.

Current evidence from the COVID-19 pandemic suggests that neonatal SARS-coronavirus-2 infections usually have a mild course. Data on how maternal infection during pregnancy affects fetal development are scarce. We present the unique case of a moderate preterm infant with intracranial bleeding and periventricular leukomalacia as a potential consequence of post-COVID-19 hyperinflammation during pregnancy.

Introduction: Monodactylous longitudinal melanonychia (LM) may represent both benign and malignant dermatologic disorders. However, squamous cell carcinoma in situ (SCCis) is not commonly considered in this setting. Case Presentation: In this report, we present 2 cases of SCCis of the nail matrix in patients with skin of color who presented with monodactylous LM involving the lateral aspect of the nail. Conclusion: These cases suggest that SCCis should be included in the differential diagnosis for monodactylous LM, especially when involving the lateral nail plate in darker skin.

Background: The lesions of porokeratosis (PK) lead to skin atrophy and scarring as long as they spread centrifugally. PK affecting the nail unit is seldom described. Objective: The aim was to revise the previously reported cases of ungual PK and to present 3 new cases. Methods: A PubMed search was performed with the keywords “nail” and “porokeratosis.” Previously reported cases as well as 3 new cases are depicted in tables. Results: Only 11 cases of ungual PK were found; 3 new cases have been added. All patients presented with typical lesions of PK (Mibelli, isolated, segmental, or ostial eccrine types) that happened to affect nails due to nail matrix or nail bed compromise, resulting in mild to severe nail scarring, including irreversible anonychia. The present 3 case series contrast with the previous single case reports. Conclusions: PK affecting the nails is exceedingly rare. Changes in nails affected by PK are irreversible, since, as on the skin, this is a chronic scarring process.

Alopecia neoplastica (AN) is caused by neoplastic cells damaging hair follicles, resulting in patchy hair loss like cicatricial alopecia and alopecia areata. AN has predominantly described cutaneous metastasis to the scalp from primary visceral malignant tumors. Less frequently, AN results from a primary scalp neoplasm. Compared to “secondary AN,” there is a paucity of literature on “primary AN.” Herein, we present a comprehensive literature review of primary AN and introduce a unique case of amelanotic melanoma causing primary AN. Including our presented case, 11 cases of primary AN have been reported with causative scalp neoplasms including angiosarcoma, hemangioendothelioma, syringomatous carcinoma, ectopic extramammary Paget’s disease, and primary desmoplastic melanoma. 27.3% (3 of 11) of cases were misdiagnosed and treated for a primary alopecia, and 36.4% (4 of 11) of lesions were present for multiple years or an unknown amount of time, likely due to difficulty in recognizing scalp lesion or misdiagnosis. All patients required surgical excision with 36.4% (4 of 11) requiring chemotherapy, radiation, or photodynamic therapy. Two patients with scalp angiosarcoma died from their aggressive disease. Due to the risks of malignant primary AN if allowed to progress, primary AN should be considered in patients presenting with scarring alopecia.

Introduction: Reticulated hyperpigmentation is a relatively uncommon dermatologic pattern. It is used to describe brown-colored skin lesions that manifest in a lacy or net-like distribution. When a clinician encounters a patient with reticulated hyperpigmentation, its location is often the most helpful feature in establishing a differential diagnosis. As this pattern is rarely observed on the scalp, this site is currently not included in the diagnostic approach. Case Presentation: In this report, we present a case of lichen planopilaris (LPP) in a black man who presented with reticulated hyperpigmentation over the scalp. Conclusion: We suggest that it may be warranted to add LPP to the differential diagnosis of reticulated hyperpigmentation, especially when arising on the scalp of darker skinned individuals.

Kaufman oculocerebrofacial syndrome is a rare autosomal recessive disorder which represents a phenotype mainly involving craniofacial and neurodevelopmental manifestations due to UBE3B gene mutations. The vast majority of the affected individuals exhibit microcephaly, eye abnormalities, and typical facial gestalt including blepharophimosis, ptosis, telecanthus, upslanting palpebral fissures, dysplastic ears, and micrognathia. We encountered 2 siblings in whom severe psychomotor delay, distinctive facial features, hearing loss, and respiratory distress were observed. Some clinical manifestations of the patients, including epibulbar dermoid, microtia, and multiple preauricular tags, were reminiscent of the oculoauriculovertebral spectrum. However, 2 affected siblings exhibited a similar clinical picture consisting of microcephaly, severe developmental and cognitive disabilities, failure to thrive, and dysmorphic features, which were not fully consistent with oculoauriculovertebral spectrum. Also, hypoplastic nails, considered as a core manifestation of Coffin-Siris syndrome, were present in our patients. Therefore, whole-exome sequencing was carried out in order to identify the underlying genetic alterations, contributing to the complex phenotype shared by the 2 siblings. A homozygous pathogenic mutation was found in both affected siblings in the UBE3B gene which caused Kaufman oculocerebrofacial syndrome. Kaufman oculocerebrofacial syndrome should be considered among the autosomal recessive causes of blepharophimosis-mental retardation syndromes, particularly in populations with a high rate of consanguineous marriages, even if there are dysmorphic facial features that are not typically associated with the phenotype.

Background: The aim of this study was to report 2 cases of pulmonary air embolism developing several hours after choroidal melanoma endoresection without the use of air infusion during the surgery, with fatality in 1 patient. Methods: The method of this study was case report. Participants: Two patients with large choroidal melanomas who collapsed several hours after endoresection without air infusion as a result of pulmonary air embolism. Results: A 72-year-old man collapsed 4 h and 30 min after endoresection without air infusion. Computerized tomography angiography confirmed air embolism. The patient died after 86 min of cardiopulmonary resuscitation. A 41-year-old woman collapsed 5 h and 30 min after endoresection, performed without air infusion and with close monitoring, which included right internal jugular vein catheterization intraoperatively. Transthoracic and transesophageal echography, performed preoperatively, intraoperatively, and postoperatively, revealed air embolism only after collapse occurred. Imaging showed the embolism to be biventricular because of patent foramen ovale. The patient was treated promptly with extracorporeal membrane oxygenation and mechanical ventilation, which resulted in a full recovery. Conclusions: Air embolism can develop after endoresection for choroidal melanoma, despite avoiding air infusion. Further studies are needed to understand how this occurs. Special measures are indicated to detect this complication and to treat it promptly and effectively.

Frontal fibrosing alopecia (FFA) is an acquired primary lymphocytic cicatricial alopecia characterized by frontotemporal hairline recession, leading to scarring alopecia with a band-like distribution. Prevalence is increasing worldwide, being the most frequent cause of primary scarring alopecia. The natural history of this condition is variable; however, slow progression with spontaneous remission is the most frequent reported outcome. The etiopathogenesis of FFA remains to be elucidated; numerous hypotheses concerning hormonal effects, environmental factors, and genetic predisposition have been proposed. Special interest on genetic basis has emerged since the first familial case was reported. Only a few more familial cases have been published. We report 6 additional cases of female patients with familial FFA (F-FFA) from 3 different families. Sixty-six percent had a family history of autoimmune disease in first-degree relatives; these same patients had a personal history of autoimmune disease. The families described in this cohort study plus the personal and family history of autoimmune disease, as well as the recently described involved genomic loci; reinforced the hypothesis of this disease being genetic. It is important to consider studying this entity since there are scarce data regarding familial cases and this might give us a better insight toward understanding its pathogenesis.

We report a case of an uncommon presentation of Epstein-Barr virus (EBV)-associated plasma cell neoplasm in a patient with a history of prostate cancer and hairy cell leukemia (HCL) in remission after chemotherapy. The diagnosis of an EBV-associated plasma cell neoplasm was challenging as initially the findings were also compatible with a recurrence of HCL. We highlight the value of diagnostic vitrectomy to achieve the diagnosis. Our particular case demonstrates the importance of diagnostic pars plana vitrectomy and aqueous analyses in patients with uveitis of an unknown cause to confirm the diagnosis.

Granular parakeratosis (GP) is a distinctive acquired keratotic dermatosis that is usually presented with brownish-red hyperkeratotic papules and plaques in the intertriginous areas. Follicular involvement in GP could be either extending lesions from interfollicular epithelium or originating primarily from the follicular epithelium. The latter was named follicular GP and is considered an extremely rare condition. To our knowledge, there has been one reported case so far in the literature. We herein report the second case of follicular GP in a 52-year-old Thai man presenting with multiple tiny filiform hyperkeratotic papules on his face 2 weeks after using anti-melasma cream. We also propose a classification of GP based on its distinct clinical manifestations and histopathological findings.

Introduction: Scalp rosacea is scarcely reported in the literature, but it is probably not uncommon. Trichoscopic findings have not been specifically established for this entity. Case Presentation: We report 4 cases of chronic scalp rosacea with trichoscopic evidence of peripilar scaling that resolved without scarring after treatment. Discussion/Conclusion: Chronic and persistent inflammation around the isthmus produced in scalp rosacea may form peripilar scaling resembling that found in lichen planopilaris.