Unusual phenotypes in patients with a pathogenic germline variant in DICER1

Pathogenic germline DICER1 variants are associated with pleuropulmonary blastoma, multinodular goiter, embryonal rhabdomyosarcoma and other tumour types, while mosaic missense DICER1 variants in the RNase IIIb domain are linked to cause GLOW (global developmental delay, lung cysts, overgrowth, and Wilms’ tumor) syndrome. Here, we report four families with germline DICER1 pathogenic variants in which one member in each family had a more complex phenotype, including skeletal findings, facial dysmorphism and developmental abnormalities. The developmental features occur with a variable expressivity and incomplete penetrance as also described for the neoplastic and dysplastic lesions associated with DICER1 variants. Whole exome sequencing (WES) was performed on all four cases and revealed no further pathogenic or likely pathogenic dominant, homozygous or compound heterozygous variants in three of them. Notably, a frameshift variant in ARID1B was detected in one patient explaining part of her phenotype. This series of patients shows that pathogenic DICER1 variants may be associated with a broader phenotypic spectrum than initially assumed, including predisposition to different tumours, skeletal findings, dysmorphism and developmental abnormalities, but genetic work up in syndromic patients should be comprehensive in order not to miss additional underlying /modifying causes.

The Accompaniment Skeletal Findings in Traumatic Pelvic Injuries in Public Tertiary Hospitals in Southwestern Nigeria

Aim: This study evaluated the attendant skeletal fracture accompaniments in traumatic pelvic fractures using plain radiography. Study Design: A prospective cross sectional study. Place and Duration of Study: The Accident and Emergency Departments of three hospitals namely; Lagos University Teaching Hospital, National Orthopedic Hospital, Igbobi, and Lagos State Health Service Commission’s Accident and Emergency Services Hospitals (LASEMS) between January 1st and December 31st 2009.). Methodology: One hundred (100) patients of all ages diagnosed by plain radiography with pelvic traumatic injury were recruited from the hospitals stated above. There were 51males and 49 females. The sociodemographic and clinical data of the patients as well as the radiographic skeletal findings and types of trauma were entered into a Microsoft excel database for cleanup and statistical analysis. Statistical analysis was done using Epi Info Version 6 Statistical Software on an IBM-compatible computer., Results: Forty two (42) patients in sex distribution of sixteen (16) males and twenty six (26) females presented with sixty seven (67) different categories of accompaniment skeletal fractures. Injuries to the femur, limb shortening and head injuries were found in decreasing order.

Radiographic findings of Desbuquois dysplasia

Desbuquois dysplasia is an autosomal recessive chondrodysplasia characterized by severe micromelic dwarfism, joint laxity, progressive scoliosis, and advanced carpotarsal ossification. Two different types of Desbuquois dysplasia have been identified according to the presence (Type 1) or absence (Type 2) of characteristic hand abnormalities including bifid distal thumb phalanx, an extra ossification center distal to the second metacarpal, and interphalangeal joint dislocations. Further, Kim et al have described a milder variant of Desbuquois dysplasia characterized by short stature and hands with short metacarpals, elongated proximal and distal phalanges, and extremely advanced carpal ossification. Here, we present a 19-year-old male patient with Kim variant of Desbuquois dysplasia. He displays almost all of the characteristic skeletal findings of Desbuquois dysplasia along with the characteristic hand features described by Kim et al. This patient is unique in that he also presents sagittal femoral bowing, a radiographic finding that accompanies various skeletal dysplasias but has never been reported in a patient with Desbuquois dysplasia to date.

IDENTIFIKASI AWAL DAN REKONSTRUKSI ASPEK BIOLOGIS TEMUAN RANGKA MANUSIA LJ-1 SITUS LEANG JARIE, MAROS, SULAWESI SELATAN

The purpose of this study is to provide an explanation of the physical aspect reconstruction effort one of the human skeletal findings that once bathed the Maros karst area. The results of excavations in 2018 and 2019 found a human skeleton at the Leang Jarie Site (LJ-1) associated with the Toalian techonology stone tools and Austronesian earthenware, with age 2700 BP. Morphometric analysis of the LJ-1 framework on the skeletal part that remains and can be recognized, known that the sex is a male aged 35-40 years with a height of 166 cm, originating from the Austronetian nation. This framework is considered as important data and evidence of human presence as ancestors of the inhabitants of the Maros cultural region, which provides evidence of the relationship between the Austromelanes race (the Toalian people) and the Mongoloid race (Austronesian people). the technology found in one context with this framework is bone artifacts in the form of Bone point, Maros point, mollusca shell kitchen waste and some pottery fragments. The results of this study can provide a new perspective on racial interactions (Austromelanesoid with Austronesian) in the past. Tujuan penelitian ini adalah untuk memberi penjelasan tentang usaha rekonstruksi aspek fisik salah satu temuan rangka manusia yang pernah mendiami kawasan karst Maros. Hasil ekskavasi tahun 2018 dan 2019 menemukan rangka manusia di Situs Leang Jarie (LJ-1) berasosiasi dengan alat batu teknologi Toalian dan gerabah Austronesia, dengan umur 2700 BP. Analisis morfometri terhadap rangka LJ-1 pada bagian rangka yang masih tersisa dan dapat dikenali, diketahu bahwa berjenis kelamin adalah laki-laki, berusia 35-40 tahun dengan tinggi badan 166 cm, berasal dari bangsa Austronesia. Rangka ini dianggap sebagai data dan bukti penting kehadiran manusia sebagai leluhur penghuni wilayah budaya Maros, yang memberikan bukti terjadinya relasi antara ras Austromelanesoid (bangsa Toalian) dengan ras Mongoloid (bangsa Austronesia. Adapun teknologi yang ditemukan dalam satu konteks dengan rangka ini adalah artefak tulang berupa lancipan (bone point), artefak batu (maros point), sampah dapur cangkang moluska dan beberapa fragmen tembikar. Hasl penelitian ini dapat memberikan perspektif barun tentang intereaksi antara ras (Austromelanesoid dengan Austronesia) yang melahirkan suatu bentuk akulturasi buadaya yang terjadi pada masa lampau.

SITUS LAMBANAPU: DIASPORA AUSTRONESIA DI SUMBA TIMUR

Abstract, Lambanapu Site: Diaspora Austronesia In East Sumba. The research at Lambanapu Site aims to determine the position of Lambanapu in the distribution and development of Austronesian ancestors and their culture in Sumba. The method used is survey, excavation, analysis, and interpretation. The results of the research are skeletal findings and urn burial also artifacts which are pottery, beads, metal jewelry, and stone tools. From the dating result it is known that Lambanapu Site was inhabited at least 2.000 years ago and from paleantropology analysis, it is estimated that the individuals found from primary and secondary burial in Lambanapu are a mixture of Mongoloid and Australomelanesoid. Genetic mixing is very possible, given the history of the archipelago's occupation which was filled by several waves of great migration in the past. The Lambanapu site has provided an overview of Sumba's ancestral life in the context of the archipelago. The Lamabanapu research results show us, how Lambanapu and Sumba in general rich with historical and cultural values of the past that are very useful for today's life. The wealth of historical and cultural values is not only for local interests, but also to fill the rich history and culture of the archipelago, and even contribute to global history. Keywords: Lambanapu, prehistoric, Austronesian Abstrak, Penelitian di Situs Lambanapu bertujuan untuk mengetahui posisi Lambanapu dalam persebaran dan perkembangan leluhur Austronesia dan budayanya di Sumba. Metode yang dilakukan adalah survei, ekskavasi, analisis, dan interpretasi. Hasil penelitian berupa temuan rangka dan kubur tempayan serta artefak berupa gerabah, manik-manik, perhiasan logam, dan alat batu. Dari hasil pertanggalan diketahui bahwa setidaknya Situs Lambanapu telah dihuni 2.000 tahun yang lalu. Hasil analisis paleoantropologi diperkirakan individu yang ditemukan di Lambanapu, baik kubur primer maupun sekunder, merupakan percampuran antara Mongoloid dan Australomelanesoid. Percampuran genetika memang sangat memungkinkan terjadi mengingat sejarah hunian Nusantara yang terisi oleh beberapa gelombang migrasi besar pada masa lampau. Situs Lambanapu telah memberikan gambaran kehidupan leluhur Sumba dalam konteks Nusantara. Hasil penelitian memperlihatkan betapa Lambanapu dan Sumba pada umumnya memiliki kekayaan nilai sejarah dan budaya masa lampau yang sangat bermanfaat bagi kehidupan masa kini. Kekayaan nilai sejarah dan budayanya tidak hanya untuk kepentingan lokal, tetapi juga untuk mengisi kekayaan sejarah dan budaya Nusantara, bahkan kontribusi bagi sejarah global. Kata kunci : Lambanapu, prasejarah, Austronesia

A clinical review and introduction of the diagnostic algorithm for thalidomide embryopathy (DATE)

Thalidomide embryopathy results from the ingestion of thalidomide in the first trimester during pregnancy, causing multiple forms of congenital abnormalities of variable severity that involve all systems. The skeletal findings most frequently affect the limbs, particularly the upper limbs and hands. Increasingly, several genetic disorders with similar birth defects have been identified. New cases of malformations owing to possible exposure to thalidomide continue to present through both historical and current usage. However, inadequate proof of ingestion, marked phenotypic variation and the possibility of an alternative genetic condition, hinder the diagnosis of thalidomide embryopathy. We introduce a ‘diagnostic algorithm for thalidomide embryopathy’ (DATE) diagnostic software that can potentially provide a numerical score for the likelihood of birth defects in an individual as being caused by exposure to thalidomide and to provide a differential diagnosis based on the pattern of malformation.