The skeletal anatomy of mandibulofacial dysostosis (Treacher Collins syndrome)

Three-dimensional osseous surface re-formation imaging from CT scans was used to examine the facial skeletons of 14 living patients with mandibulofacial dysostosis. Partial to complete aplasia of the zygomatic process of the temporal bone, mild hypoplasia to aplasia of the frontal process of the zygoma, antimongoloid slant of the transverse orbital axis, and hypoplasia of the medial pterygoid plates and muscles are common to all patients examined. Deformities of the zygoma, zygomatic process of the frontal bone, mandible, and lateral pterygoid plates and muscles vary from minimal to severe, including aplasia. The body of the zygoma is the least affected part of the bone. Right-left asymmetry characterizes these deformities in all patients. The most consistent skeletal aplasia (cleft) in mandibulofacial dysostosis involves the zygomatic process of the temporal bone rather than the zygoma itself.     

Aplasia of tibia with split-hand/split-foot deformity. Report of six families with 35 cases and consideration about variability and penetrance

Summary Six families with a total of 34 affected persons with the syndrome of tibial aplasia and ectrodactyly are reported. The spectrum of malformations is compared to that of 99 familial cases from the literature. The full-blown syndrome consists of bilateral aplasia of tibiae and split-hand/split-foot deformity. Additional malformations may be distal hypoplasia or bifurcation of femora, hypo- or aplasia of ulnae, and minor anomalies such as aplasia of patellae, hypoplastic big toes, postaxial and intermediate polydactyly in connection with split-hand deformity, and cup-shaped ears. The mildest visible manifestation may be hypoplastic big toes, the severest is tetramonodactyly or transverse hemimelia. This disorder is autosomal dominantly inherited. The penetrance is markedly reduced.     

Unilateral longitudinal radial ray deficiency of the hand and metacarpal 4-5 synostosis

We report 3 non related patients with severe hypoplasia/aplasia of the thumb with an ipsilateral synostosis of the fourth and fifth metacarpals. A review of few reports on this unusual association is presented and the possible pathogenetic mechanism is discussed.     

Pathology of amniogenesis in the early prenatal period of human development

Morphological and, in a number of cases, cytogenetical investigation has been performed in 420 intact embryonal sacs and in embryos 7-8-week-old, obtained at spontaneous abortions (272) and at tubal pregnancy (148). Among these cases 202 (48.1%) intact empty embryonal sacs, 75 (17.9%) embryos with panorganodysplasia, 25 (6%) embryos with isolated developmental defects and 118 (28%) phenotypically normal embryos have been revealed. Pathology of amniogenesis such as aplasia or hypoplasia of the amniotic cavity is noted in 136 (32.4%) cases. Among 75 embryos with panorganodysplasia anomalies such as hypoplasia of the amniotic cavity in combination with a partial extra-amniotic++ position of the embryos in exocelom (10.7%), aplasia (5.3%) or hypoplasia (17.3%) amniotic peduncle is present in 43 (57.3%) observations. Out of 40 such cases at spontaneous abortions, cytogenetically investigated, in 27 (67.5%) chromosomal disorders (tetraploidy, triploidy, autosomal trisomy and monosomy) are revealed. Aplasia and hypoplasia of the amniotic cavity are considered as pathology of histogenesis at the tissue stage of the early human ontogenesis, that most evidently occurs as a result of asplasia, destruction or anomaly of embryoblast during the first phase of gastrulation on the 7th-11th day of the intrauterine development.     

Ectrodactyly/split hand feet malformation

Split-hand/split-foot malformation is a rare limb malformation with median clefts of the hands and feet and aplasia/hypoplasia of the phalanges, metacarpals and metatarsals. When present as an isolated anomaly, it is usually inherited as an autosomal dominant form. We report a case of autosomal recessive inheritance and discuss the antenatal diagnosis, genetic counseling and treatment for the malformation.     

Fibrodysplasia ossificans progressiva

Fibrodysplasia ossificans progressiva is a rare autosomal dominant genetic disorder and the most disabling condition of heterotopic ossification in humans. Congenital malformation of the great toes in terms of hypoplasia or aplasia and fibular deviation is noted in almost all patients, and a hypoplasia of the thumbs in about half of the patients. Mutations in the ACVR1 gene were identified as a genetic cause of FOP. We summarize the clinical and molecular data of 25 patients from our cohort as well as of 47 patients with known mutations, and the clinical information described in the literature so far. We discuss these summarized data in terms of genotype-phenotype correlation.     

Pathomorphological changes in an early spontaneous abortus with triploidy (69,XXX)

Summary Triploid (69,XXX) spontaneous abortus with a gestational age of 14–15 weeks (anatomical age of the embryo was 6 weeks) was analyzed macro- and microscopically. There were hydatidiform swelling and cystic degeneration of the villi, without proliferation of the trophoblast of cells, aplasia of one umbilical artery. The embryo had the following anomalies: cranial and caudal hypoplasia; aplasia of the facial structures (aprosopia), ocular vesicles, nasal stalk, extremity buds, somites, upper jaw, hyoid and pharyngeal arches, esophagus; trachea, Rathke's pouch and oropharyngeal cavity; encephalocele, focal anomalous rudiments of cartilage in the chordamesoderm, atresia of the stomodeal foramen and persistance of the lenticular placode.     

Clinical and pathological studies on the Mauritian Pink Pigeon Columba mayeri

Six Pink Pigeons Columba = Nesoenas mayeri from the captive breeding project on Mauritius which showed a range of physical abnormalities were examined clinically and post mortem. Significant findings included a pedal deformity in several birds and cerebellar hypoplasia/aplasia in another. Parasites were not detected and none of the birds showed serum antibodies to Newcastle disease virus, Paramyxovirus or Chlamydia psittaci. The results are of relevance to the captive breeding and management of this endangered species.     

Digeorge anomaly associated with partial deletion of chromosome 22. Report of a case with X/22 translocation and review of the literature

Partial monosomy of 22q, resulting from a de novo unbalanced translocation t(X;22)(q28;q11) was detected in a newborn female with manifestations of the DiGeorge anomaly including multiple anomalies, type I truncus arteriosus, T-cell abnormalities, thymic aplasia and parathyroid hypoplasia noted on postmortem examination. Although DiGeorge anomaly is causally heterogeneous, our patient, together with 18 previously known cases, confirm that partial monosomy of the proximal long arm of chromosome 22 is the single most common cause of this polytopic developmental field defect.     

Brief communication: The size of the human frontal sinuses in adults presenting complete persistence of the metopic suture

The notion of absence of the frontal sinuses in human individuals presenting a persistence of the metopic suture is considered as classical in many treatises of reference; however, precise studies are very rare and even controversial. The purpose of this study was thus to provide original data to confirm or refute this classical affirmation with the perspective of some original insights into biological significance of the frontal sinuses and the factors influencing their exceptional polymorphism. The material consisted of 143 dry skulls of adult individuals (European Homo sapiens), distributed in two groups: 80 skulls presenting a complete frontal closure with total disappearance of the metopic suture, and 63 skulls presenting a complete persistence of the metopic suture. Each skull was radiographed in oblique projection using the occipitomental view. A simple morphological quantification of the sinus size was defined with four categories: (1) aplasia, (2) hypoplasia, (3) medium size, (4) hyperplasia. Statistically significant difference in frontal sinusal size was found between both groups of skulls. Absent and small sinuses were considerably more frequent in skulls with persistence of the metopic suture (57.9 vs. 11.9%): small frontal sinuses (hypoplasia) were much more frequent (50.8 vs. 9.4%), although the frequency of absence of frontal sinuses (aplasia) was only slightly higher (7.1 vs. 2.5%). Am J Phys Anthropol 154:621–627, 2014. © 2014 Wiley Periodicals, Inc.     

Anterior thoracic hypoplasia: a separate entity from Poland syndrome

SUMMARY: Women presenting with anterior thoracic depression, breast hypoplasia, and subsequent asymmetry are often diagnosed with Poland syndrome regardless of pectoralis involvement, or are placed in the generic category of breast asymmetry or skeletal dysplasias. Recently, though, the term "sunken chest" has been used to describe forms of chest wall depression that previously may have fallen under generic skeletal dysplasias. The authors believe that, combined with hypoplasia of the ipsilateral breast, superior location of the nipple-areola complex compared with the contralateral side, and normal pectoralis muscles, this represents a previously undefined and real condition called anterior thoracic hypoplasia. During the past 4 years, the authors have treated eight women who have presented with a diagnosis of Poland syndrome or pectus excavatum, all of whom share the same characteristics-unilateral sunken anterior chest wall, hypoplasia of the breast, superiorly placed nipple-areola complex, normal pectoralis muscle, and normal sternal position. All of the patients underwent correction of breast asymmetry and unilateral anterior thoracic hypoplasia with augmentation mammaplasty, a method that when tailored for each side yields good aesthetic results. The average age of the patients was 31 years and the average chest size was 34. Cup size, as measured by the patient's standard bra, was a B on the nonaffected side in all patients and an A on the affected side in all patients except one. Of the eight patients, seven had the right anterior chest and breast involved, whereas one patient had involvement on the left. For all of the patients, the nipple and areola of the hypoplastic side were smaller and in a more superior position compared with the contralateral side on visual inspection. In the eight patients, a total of 19 augmentations (15 primary augmentations and four revisions) and one mastopexy were performed. Ten inframammary-fold approaches and nine periareolar approaches were used, and all of the implants were placed in a partial submuscular position, except for two implants placed in a subglandular position that were converted to partial submuscular positions in a secondary setting. In all the women, the sternal head of the pectoralis muscle was present and the pectoralis muscle appeared to be equal in size compared to the contralateral side. Nine different types of implants were used. Average implant fill volume measured 412 cc on the hypoplastic side and 257 cc on the contralateral side. In follow-up, all of the patients were satisfied with their operation and rated their aesthetic outcome as very good to excellent. The authors believe that anterior thoracic hypoplasia is a real, previously misdiagnosed and undescribed condition, and that both chest wall and breast deformities can be corrected safely and with excellent results using proper augmentation planning and implant selection.     

Pathogenesis of radiation-induced abnormalities of the bones and joints of white rat embryos

After X-radiation of pregnant rats on the 10th day of pregnancy, in 50% of the fetuses studied subtotal aplasia of the tibial bone anlage and decreasing number of the metatarsus and finger phalanges anlages are observed. Radiation on the 11th day of embryogenesis does not result in anomaly formation of the thoracic and pelvic extremities. After radiation on the 12th day of embryogenesis, the most specific anomaly of the pelvic extremity is phocomelia. The thoracic extremity skeleton lesions are revealed as an ulnar type of distal ectromelia, or axial ectromelia. After radiation on the 13th--14th day, hypoplasia of the bone anlages, that make zeugopodium, autopodium, is observed. After radiation on the 13th day, a partial or total aplasia of the fibular bone anlage can take place. In all the fetuses a sharp decrease in number of the hand and foot bone anlages is observed; it is connected with a total aplasia of some of them and with fusion of the others. A specific feature for radiation lesions of the extremity skeleton is that the oppositely situated anlages of the bones do not separate from each other. This results from certain disturbances in the joint interzone formation at early stages of embryogenesis and from underdevelopment of the joint cleft. Qualitatively different radiation anomalies of the extremity skeleton development are formed as consequence of disturbances in morphogenetic processes of determination: migration, proliferation, morphogenetic cell death and differentiation.     

Ontogeny of the leg muscle tissue in the crooked neck dwarf mutant (cn/cn) chick embryo

The crooked neck dwarfism (cn/cn) is characterized, among other anomalies, by a muscular hypoplasia, particularly conspicuous in the tibiotarsal segment. Histological observations were performed between day 6 and day 12.5 of incubation. They show, in the tibiotarsal segment, that the hereditary muscular hypoplasia is not caused by a defect of the normal muscular splitting pattern. Indeed, in the mutant, the splitting of muscle masses proceeds normally up to the last partition (day 7-7.5), but is followed by the secondary fusion of individuated muscles into an unpatterned muscle tissue. Thus the mutant phenotype is the result of an inability of the muscle pattern to become stabilized into definitive structures.     

Cloning and characterization of a novel human ubiquitin-specific protease, a homologue of murine UBP43 (Usp18)

The ubiquitin-specific proteases (UBP) are a family of enzymes that cleave ubiquitin from ubiquitinated protein substrates. We have recently cloned UBP43, a novel member of this family from AML1-ETO knock-in mice. To analyze the role of UBP43 in hematopoiesis and leukemogenesis, we have cloned a full-length human UBP43 cDNA by screening a human monocytic cDNA library as well as by 5'- and 3'-rapid amplification of cDNA ends analyses. This cDNA encodes a polypeptide of 372 amino acids with all of the structural motifs of a deubiquitinating enzyme. The human UBP43 mRNA is strongly expressed in human liver and thymus. Transfection analysis has demonstrated that UBP43 is a nuclear protein. Interestingly, the gene encoding human UBP43 maps to chromosome 22q11.2. This region, known as DiGeorge syndrome critical region, contains a minimal area of 2 Mb and is consistently deleted in DiGeorge syndrome and related disorders. The syndrome is marked by thymic aplasia or hypoplasia, parathyroid hypoplasia, or congenital cardiac abnormalities. Taken together, our results broaden the understanding of a new human ubiquitin-specific protease, UBP43, and suggest that this gene may also be related to DiGeorge syndrome.     

Abnormalities of the nuclear envelope in porcine muscle affected with congenital myofibrillar hypoplasia.

The nuclear ultrastructure of muscle fibres in congenital myofibrillar hypoplasia of piglets was studied in order to provide more information on the pathological changes present. In the initial stages of the disease, muscle fibres with a small reduction of myofibrils often had an increased number of nuclear pores. In the more advanced stages of the disease, the following nuclear abnormalities were observed in muscle fibres showing an extensive disintegration of myofibrils: 1) large dilations of the perinuclear cisternae, 2) small nuclear protrusions projecting into these dilations and 3) appositions of stray membranes of the disrupted endoplasmic reticulum to the nuclear envelope. The increase in the number of nuclear pores may be significant in the development of pathological changes in congenital myofibrillar hypoplasia which is thought to be a hereditary disease. The observed abnormalities of the nuclear envelope appear to be characteristic for muscle fibres undergoing degeneration.     

Reconstruction of mammary hypoplasma associated with chest wall deformities.

Three young women who had significant unilateral hypoplasia of the breast, accentuated by marked rib deformities and hypoplasia of the pectoralis muscle, were treated by two-staged reconstructions. A custom-made chest wall implant and a breast prosthesis were used. In the absence of cardiorespiratory compromise, these are simpler operations than rib osteoplasties and the cosmetic result is better.     

Limb mammary syndrome: a new genetic disorder with mammary hypoplasia, ectrodactyly, and other Hand/Foot anomalies maps to human chromosome 3q27.

We report on a large Dutch family with a syndrome characterized by severe hand and/or foot anomalies, and hypoplasia/aplasia of the mammary gland and nipple. Less frequent findings include lacrimal-duct atresia, nail dysplasia, hypohydrosis, hypodontia, and cleft palate with or without bifid uvula. This combination of symptoms has not been reported previously, although there is overlap with the ulnar mammary syndrome (UMS) and with ectrodactyly, ectodermal dysplasia, and clefting syndrome. Allelism with UMS and other related syndromes was excluded by linkage studies with markers from the relevant chromosomal regions. A genomewide screening with polymorphic markers allowed the localization of the genetic defect to the subtelomeric region of chromosome 3q. Haplotype analysis reduced the critical region to a 3-cM interval of chromosome 3q27. This chromosomal segment has not been implicated previously in disorders with defective development of limbs and/or mammary tissue. Therefore, we propose to call this apparently new disorder "limb mammary syndrome" (LMS). The SOX2 gene at 3q27 might be considered an excellent candidate gene for LMS because the corresponding protein stimulates expression of FGF4, an important signaling molecule during limb outgrowth and development. However, no mutations were found in the SOX2 open reading frame, thus excluding its involvement in LMS.     

Distal trisomy 10q and limb defects

Analysis of the literature showed that hypoplasia (or aplasia) of tibiae was found at least in six persons with trisomy 10q25.2-qter. Therefore, these defects should be considered as a characteristic manifestation of the distal trisomy 10q. In most of these patients, tibial abnormalities were associated with other defects of the lower extremities (hypoplastic femora, ectrodactyly, preaxial polydactyly). Upper limbs were affected in one patient (as well as in her sib without tibial defects). Most likely, segment 10q25.2-qter contains a gene which (when triplicated) leads to maldevelopment of the limbs, and tibial malformations are only one manifestation of this field defect.