Chest wall deformities and their possible associations with different genetic syndromes.

OBJECTIVE: Our primary objective was to identify discrete and syndromic cases of Pectus excavatum (PE) and Pectus carinatum (PC). We also intended to highlight the significance of further genetic exploration in clinically suspected syndromic cases of PC and PE. Pectus excavatum (PE) and Pectus carinatum (PC) are the most common morphological chest wall deformities. Although various hypotheses have been put forth, the pathogenesis of both entities is largely unknown. Clinicians often refer such cases for further genetic evaluation to exclude an associated underlying connective tissue disorder or a syndrome. Additionally, a detailed anamnesis with focused family history and thorough dysmorphological physical examination was done. PE and PC are considered isolated abnormalities if there is the absence of features of other syndromes, eliminating the need for further genetic evaluations. It is believed that the pattern of inheritance of these non-syndromic isolated PE and PC cases with positive family history could be multifactorial in nature. The recurrence risk of such isolated cases is thought to be low. Further diagnostic studies are indicated as PE and PC could be a part of a syndrome. Among the many syndromes, the most common monogenic syndromes associated with PE and PC are Marfan's and Noonan's. PATIENTS AND METHODS: After obtaining the consent, we compiled a database of the patients who presented with chest wall deformities during the period 2017-2019. We selected 70 cases with PC and PE deformities to identify the discrete and syndromic PC and PE cases. During the study, we perused the cytogenetic and/or molecular analyses, that had been conducted to confirm the clinically suspected syndromic cases. We also scrutinized for the presence of PC and PE cases that are associated with the rare syndrome (s). RESULTS: Various genetic abnormalities were identified in 28 (40%) of the 70 cases that had been diagnosed with chest wall abnormalities. Along with PE and PC, other thoracic wall abnormalities were also identified, such as the broad chest, bell-shaped thorax, and elongated or enlarged thorax. One case of a rare genetic disorder of Morquio syndrome associated with PC was also identified. Novel (previously unpublished) genomic variants are reported here. CONCLUSIONS: It is important to delve deeper when encountering cases of PE and PC by conducting a further genetic exploration of such cases to identify syndromic associations that cause other structural and functional disorders, diagnosis of which might be missed during the early developmental period. Early identification of such disorders may help us correcting the defects, slowing the progression of disease processes, and preparing better to deal with the potential outcome.

Lethal evolution of a newborn with consistent features of hydrolethalus syndrome--Romanian patient.

Hydrolethalus syndrome is a severe lethal disorder most commonly found in Finland. We present a lethal case of complex congenital malformation in a Romanian family who showed multiple signs described in hydrolethalus syndrome. Our case presented the specific characteristics: macrocephaly, midline cleft-lip, cleft palate, polydactyly of both hands and feet but without occipitoschisis, considered as the pathognomonic sign of the syndrome. Sequencing analysis of HYLS1 did not identify the point mutation present in the Finnish cases or other mutations in this gene.

Leptospirotic etiology in pulmonary and upper respiratory tract pathology.

A number of 3,200 febrile patients who presented upon admission to hospital primary pulmonary or upper respiratory tract impairment either as single forms of manifestation or associated to other syndromes were tested. The cases were screened by the rapid slide agglutination reaction with heat inactivated Patoc antigen and leptospirotic etiology was confirmed by the ultramicroscopic agglutination reaction with 18 live circulating pathogenic antigens. 64 leptospirosis cases with pulmonary impairment were confirmed and in 52 cases the upper respiratory tract was involved. Particular aspects of leptospirosis with pulmonary impairment: 71.8% of cases had a clinical diagnosis of interstitial pneumonia; 89% of cases presented important chest x-ray modifications; in an approximately equal number of cases the pulmonary involvement was the single manifestation or was associated with other syndromes; icterohaemorrhagiae, wolffi and pomona were the frequently encountered infecting serotypes. Particular aspects for leptospirosis involving the upper respiratory tract: 84.6% of cases had a clinical diagnosis of acute rhino-pharyngotracheitis; in 86.5% of cases the upper respiratory tract impairment was the single feature; the infecting serotypes were in decreasing order of frequency as follows: icterohaemorrhagiae, pomona, wolffi, canicola, grippotyphosa.

Study of the leptospirotic etiology in the digestive pathology, particularly in acute abdomen.

The paper approaches the possible leptospirotic etiology of non-icteric or late icteric digestive manifestations: digestive hemorrhage, particularly epigastric, acute cholecystitis (non-lithiasic), acute appendicitis, acute gastroenterocolitis, etc., which can be indicative of an acute or latent (from 14 days to several months) leptospirosis. A number of 300 patients with high fever, epidemiological data relevant for leptospirosis and diagnosis upon admission to hospital were investigated using the work method presented in the paper. The synoptical table presents in detail 30 serologically confirmed leptospirosis cases; this reveals the fact that any serotype can be determining and the severe evolution may occur when the etiological diagnosis and treatment are delayed. The 1.67% incidence for the cases clinically expressed by the studied pathology points to the need to consider this pathology as a possible expression form of leptospirosis against the specific epidemiological context.

A de novo 2.3 Mb deletion in 2q24.2q24.3 in a 20-month-old developmentally delayed girl.

We report a 20-month-old girl ascertained at the age of 11 months for developmental delay. She presented with hypotonia and delayed motor development. The patient had severe language impairment and showed behaviour consistent with autism spectrum disorder. She was microcephalic with mild dysmorphic features and had joint hyperlaxity. We detected a 2.3 Mb de novo deletion in 2q24.2q24.3 on her paternal chromosome. We compare the clinical features of our patient to six previously published patients with a deletion in 2q24.2q24.3, and one patient reported in the ECARUCA database. Although the clinical presentation of these patients is not highly consistent, likely due to the different deletion size and gene content, the following features seem to be recurrent: disturbance in the central nervous system, poor growth, hypotonia, and joint hyperlaxity. The region deleted in our patient contains 13 genes including PSMD14, TBR1, SLC4A10, DPP4, KCNH7, and FIGN. We briefly review the knowledge of these genes and their possible involvement in the aetiology of this developmental delay syndrome.

Ichthyosis congenita, harlequin fetus type: a case report.

Ichthyosis is a very heterogeneous family of skin disorders with harlequin ichthyosis being the most severe genetic form. It is a rare autosomal recessive condition, characterized by dry, severely thickened skin with large plates of hyperkeratotic scale, separated by deep fissures. Infants are very susceptible to metabolic abnormalities and infections. They usually do not survive for very long, but several long term survivals have been noted. The vast majority of affected individuals are homozygous for mutations in the ABCA12 gene, which cause a deficiency of the epidermal lipid transporter, resulting in hyperkeratosis and abnormal barrier function. We report a case of a newborn with harlequin ichthyosis, born to unrelated parents, who had a favorable evolution with topical treatment and intensive care.

A new prepatory method of thermically inactivated Leptospira Patoc antigen for rapid slide agglutination used as serosurvey test for human leptospiroses.

830 sera from leptospirosis-suspect patients and 133 sera from investigations were analysed by the new test--rapid slide agglutination with Patoc antigen, inactivated at 60 degrees C for 15 minutes, in parallel with two standard tests--CFT with merthiolated Patoc antigen and MAR with 17-23 live pathogenic antigens. The new serotest proved efficient for selecting the cases of disease or leptospira infection, acute or recent form, not older than 2 years, both by its sensitivity and specificity and also by its rapid and economical character. In the present paper, the technology of preparation and control of Patoc antigen, inactivated at 60 degrees C for 15 minutes, is described.

May human leptospirosis develop as a chronic infection?

In connection with some rather uncommon cases, the authors asked themselves whether leptospirosis may also develop as a chronic infection. To answer this question, we took into consideration four of the most representative investigated cases encountered during the last 22 years. In conclusion, it appears that in some circumstances, human leptospirosis could present itself as a chronic disease.