Heritable testicular hypoplasia in Nguni (Bos indicus) bulls: vascular characteristics and testosterone production.

The biased unilateral occurrence of heritable gonadal hypoplasia was investigated by examining the gross- and microanatomy of the testicular artery and vein, testicular blood flow and testicular testosterone secretion in normal Nguni bulls and in Nguni bulls showing unilateral left, unilateral right and bilateral hypoplasia of the testis. A high incidence of branching of the testicular artery was found ipsilateral to hypoplastic testes. The branching occurs a short distance from the dorsal aorta: one branch proceeds to the testis, the other to the ipsilateral kidney. The association between arterial branching to the kidney and ipsilateral hypoplasia of the testis held for both unilaterally left and unilaterally right hypoplastic bulls. Variations in the anatomy of the testicular vein occurred in both normal and hypoplastic bulls but there was no specific association between the variations and ipsilateral hypoplasia. The lumen diameter of the testicular artery or branch correlated with testis mass. Wall thickness of the artery ipsilateral to hypoplastic testes was not different from that in normal bulls, discounting hyperplasia of the endothelium. Total blood flow to the testis correlated with testis mass. The secretion rate of testosterone from hypoplastic testes was lower than that of normal testes but there was no difference when compared on a unit mass basis.     

Fuhrmann syndrome associated with cortical dysplasia

We describe a male newborn with bilateral angle bowing of femora, absent fibulae, aplasia of the fingernails, hypoplastic toenails, malformed thumbs, hypospadias, inguinal hernia and cortical dysplasia in a consanguineous Turkish Family. The MCA syndrome in the present patient is similar to these reported in 3 affected sibling by Fuhrmann et al.     

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.     

Constitutional del(5)(q23.3q31.1)

A 4-month-old male infant with muscular hypotonia, growth and psychomotor retardation, large low-set ears, hypoplastic genitalia, right hip luxation and bilateral equinovarus, was found to have a constitutional 46,XY,del(5)(q23.3q31.1) karyotype. From the comparison with 12 similar cases, a rather characteristic clinical phenotype emerges.     

Postovariectomy bone marrow changes in irradiated and unirradiated wistar rats

Bilateral ovariectomy of Wistar rats has per se a stimulative effect on the myeloid tissue, determining a hypercellularity of this organ-tissue. On the other hand, under the conditions of a whole-body irradiation with a single dose of 800 r X-rays, bilateral ovariectomy manifests a protective effect on the myeloid tissue preventing the development of hypoplastic, respectively aplastic modifications.     

XO/XY mosaicism in a 2 year phenotypic male.

A 2-year-old male with bilateral undescended gonads, hypoplastic external auditory canals, large umbilical hernia and XO/XY chromosome mosaicism is described in this communication. Salient features of other similar cases, i.e. XO/XY mosaicism in phenotypic males, from the literature are summarized, showing the wide diversity of manifestations of this syndrome.     

De novo ring chromosome 3 in a girl with hypoplastic thumb and coloboma of iris

We describe a female child with a ring chromosome 3, found after investigation for short stature. Her karyotype was 46,XX,r(3)(p26-q29). Her phenotype mainly differs from that of the nine patients previously reported with ring chromosome 3, by the presence of hypoplastic right thumb and bilateral coloboma of the iris.     

Correspondence between enamel hypoplasia and odontometric bilateral asymmetry in Australian twins

Four aspects of enamel hypoplasia of the maxillary central incisor and mandibular canine (hypoplasia presence, width, cumulative width, and crown position) were correlated with directional and fluctuating measures of bilateral odontometric asymmetry in a large panel (n = 950) of South Australian twins. Hypoplasia and asymmetry are thought to reflect general developmental disruption, but they show few correlations beyond the expected statistical type I error. This may relate to differences in their specific etiology, the composite nature of overall crown dimensions, a general lack of stress, and the extended period of formation of dental crowns. In contrast, asymmetry is marginally more detectable in a subsample separated according to hypoplastic teeth, suggesting that correspondence may be clearer in comparisons at the population rather than individual level. The most notable difference is the greater variability of asymmetry measures in hypoplastic individuals.     

Prune perineum syndrome: report of a second case

A child is reported with a constellation of anomalies which include acetabular dysplasia with bilateral dislocated hips, persistent cloaca, hypoplastic kidney, two umbilical vessels, anal atresia and no obvious external genitalia. These anomalies are strikingly similar to a case reported by Peeden et al ('79) which was referred to as prune perineum. A discussion on possible underlying cause(s) of caudal dysplasia is included.     

Roberts' — SC phocomelia syndrome with cytogenetic findings

Summary This paper reports the physical and cytogenetic findings in an eight-year-old severely mentally retarded female child with the following features: tetraphocomelia; weight, lenght, and head circumference below the third percentile; microcephaly with prominent frontal bones; hypertelorism; shallow orbits; prominent eyes; bilateral corneal opacities; micrognathia; hypoplastic alae nasi; small, low set ears; short neck; sparse silvery blond hair; severe flexion deformities of both knees and wrist joints; a cardiac murmur. Cytogenetic studies revealed premature centromere separation.     

Monosomy 11Q: report of new phenotypic manifestations.

We present a case of new phenotypic findings not previously reported associated with a partial deletion of chromosome 11 with a break point at 23q - (46,XY,del(11)(q23). Partial deletion of chromosome 11q was first described by Jacobsen et al(4). Forty-eight patients have been reported during the last 30 years, with variable break points between 11q11 and 11qter. New phenotypic findings in our patient with the associated 11q deletion are imperforate anus, bilateral cataracts, and hypoplastic, multilobed lungs.     

Unique anomalies in cephalothoracopagus janiceps conjoined twins with implications for multiple mechanisms in the abnormal embryogenesis

The anatomic features of female conjoined twins with the Janiceps type of cephalothoracopagus are described. Abnormalities included bilateral clefts of the alveolar arches, shared rudimentary mandible, high, arched clavicles, multiple rib deformities, single shared foregut and small intestine, absent large intestines, omphalocele, multicystic kidneys, hypoplastic lungs, interconnected aortas and neck vessels, single ovary with elongated uterus in each twin, displaced labia, abnormal segmentation of the vertebrae, spinal dysraphism, diastasis of the symphysis pubis, malrotated lower extremity, bilateral posterior dislocation of the hips, and club feet. There were two hearts with internal anomalies. Both spinal cords had a myelocele in the lumbar region. The abnormalities noted in previous reports of conjoined twins of this type are reviewed and compared. We propose that factors associated with conjoining, dysgenetic (developmental) defects, and deformations resulting from crowding in utero all may have been important in the abnormal development in this case.     

A distinct osteochondrodysplasia with hypertrichosis—Individualization of a probable autosomal recessive entity

Summary Two sibs and two other unrelated patients presented a distinct previously undescribed syndrome consisting of generalized congenital hypertrichosis, macrosomy at birth, narrow thorax, cardiomegaly, wide ribs, platyspondyly, hypoplastic ischiopubic branches, small obturator foramen, bilateral coxa valga, enlarged medullar canal, long bones shaped like an Erlenmeyer flasks and generalized osteopenia. The family data suggest autosomal recessive inheritance.     

A case of acampomelic campomelic dysplasia

Acampomelic campomelic dysplasia is a rare variant of campomelic dysplasia syndrome affecting bone and connecting tissue. This syndrome is implicated by the absence of bowed limbs. Affected children have a characteristically smooth facial profile and are born with respiratory distress. A 15 day old Turkish boy presented with a small flat face, dolicocephalic head, proptotic eyes, short neck, low-set ears and a small thoracic cage. Limbs were mesomelically short and bilateral talipes equinovarus was present. The radiological findings indicated hypoplastic scapulae, narrow ribs, small thorax, thin claviculaes, and small iliac wings. Angulation of the femur, tibia and humerus was not observed. Our case, suited to acampomelic campomelic dysplasia, is discussed with differential diagnosis and compared with previously reported cases of the syndrome.     

Extrinsic fetal akinesia and skeletal development: a study in oligohydramnios sequence

Long-bone morphometry and cephalometry were performed in 13 newborns with oligohydramnios sequence (OS) in order to establish whether or not skeletal changes existed in extrinsic fetal akinesia similar to those observed in the fetal akinesia deformative sequence (FADS) (i.e., hypoplastic long bones and micrognathia). Oligohydramnios sequence was caused by bilateral renal agenesis in five cases and obstructive uropathy in eight cases. Twenty-one stillborns and newborns who had died from conditions other than renal anomalies or congenital malformations were used as controls. Normal longitudinal and periosteal long-bone growth and absence of micrognathia were found in OS patients. Skeletal differences between FADS and OS may be explained not only by timing, duration, and degree of reduced motility but also, and more importantly, by the normal muscular stress in OS patients.     

Ovarian hypoplasia in heifers due to germ cell weakness

Ovarian hypoplasia due to germ cell weakness was found in 18 heifers of the Swedish Red and White breed simultaneously with a sharp increase of the same syndrome in bulls of the same breed. The heifers were examined because they had not shown estrus or had not become pregnant after several months on pasture together with a fertile bull. After palpation of the ovaries per rectum they were classified as normal, partially hypoplastic or totally hypoplastic. The heifers were slaughtered and the numbers of primordial follicles were counted in the serially sectioned ovaries. The average numbers of follicles per ovary in the 3 diagnostic groups were 18716, 6617 and 4761, respectively. The numbers of primordial follicles in hypoplastic ovaries were significantly lower than in normal ovaries but were still within normal limits for heifers. However, the hypoplastic ovaries were very small, and the totally hypoplastic ones weighed only 1 g or less. The growth of the primordial follicles was disturbed and very few developed into Graafian follicles. There were also many empty cortical cords and anovular follicles. The heifers had all been sired by bulls belonging to breeding lines where germ cell weakness had occurred.     

Binderoid complete cleft lip/palate

A small subset of infants with complete cleft lip/palate look different because they have nasolabiomaxillary hypoplasia and orbital hypotelorism. The authors' purpose was to define the clinical and radiographic features of these patients and to comment on operative management, classification, and terminology. The authors reviewed 695 patients with all forms of incomplete and complete cleft lip/palate and identified 15 patients with nasolabiomaxillary hypoplasia and orbital hypotelorism. All 15 patients had complete labial clefting (5 percent of 320 patients with complete cleft lip/palate), equally divided between bilateral and unilateral forms. The female-to-male ratio was 2:1. Of the seven infants with unilateral complete cleft lip/palate, one had an intact secondary palate and all had a hypoplastic septum, small alar cartilages, narrow basilar columella, underdeveloped contralateral philtral ridge, ill-defined Cupid's bow, thin vermilion-mucosa on both sides of the cleft, and a diminutive premaxilla. Of the eight infants with bilateral complete cleft lip, one had an intact secondary palate. The features were the same as in patients with unilateral cleft, but with a more severely hypoplastic nasal tip, conical columella, tiny prolabium, underdeveloped lateral labial elements, and small/mobile premaxilla. Central midfacial hypoplasia and hypotelorism did not change during childhood and adolescence. Intermedial canthal measurements remained 1.5 SD below normal age-matched controls. Skeletal analysis (mean age, 10 years; range, 4 months to 19 years) documented maxillary retrusion (mean sagittal maxillomandibular discrepancy, 13.7 mm; range, 3 to 17 mm), absent anterior nasal spine, and a class III relationship. The mean sella nasion A point (S-N-A) angle of 74 degrees (range, 65 to 79 degrees) and sella nasion B point (S-N-B) angle of 81 degrees (range, 71 to 90 degrees) were significantly different from age-matched norms ( = 0.0007 and = 0.004, respectively). The ipsilateral central and lateral incisors were absent in all children with unilateral cleft, whereas a single-toothed premaxilla was typically found in the bilateral patients. Several modifications were necessary during primary nasolabial repair because of the diminutive bony and soft-tissue elements. All adolescent patients had Le Fort I maxillary advancement and construction of an adult nasal framework with costochondral or cranial graft. Other often-used procedures were bony augmentation of the anterior maxilla; cartilage grafts to the nasal tip and columella; and dermal grafting to the median tubercle, philtral ridge, and basal columella. Infants with complete unilateral or bilateral cleft lip/palate in association with nasolabiomaxillary hypoplasia and orbital hypotelorism do not belong on the holoprosencephalic spectrum because they have normal head circumference, stature, and intelligence, nor should they be referred to as having Binder anomaly. The authors propose the term cleft lip/palate for these children. Early recognition of this entity is important for counseling parents and because alterations in standard operative methods and orthodontic protocols are necessary.     

Angiopoietin-1 and VEGF in vascular development and angiogenesis in hypoplastic lungs

We hypothesized that exposure of murine fetuses to environmental toxins, such as nitrofen, during early embryogenesis alters vasculogenesis. To address our hypothesis, we assessed protein levels of endothelial cell-selective angiogenic factors: angiopoietin (ANG)-1, vascular endothelial growth factor (VEGF), and mediator of VEGF signaling, VEGF receptor-2 [fetal liver kinase (Flk)-1], a transmembrane receptor tyrosine kinase. VEGF and Flk-1 proteins were lower in hypoplastic lungs from pseudoglandular to alveolar stages than in normal lungs at equivalent developmental time points significant for induction of pulmonary vasculogenesis and angiogenesis. ANG-1 protein was higher in hypoplastic lungs than in normal lungs at all the developmental stages considered in this study, i.e., pseudoglandular, canalicular, saccular, and alveolar stages. We assessed exogenous VEGF-mediated endothelial cell response on extracellular signal-regulated kinase (ERK) 1/2, also referred to as p44/42 mitogen-activated protein kinase. Hypoplastic lungs had more elevated ERK 1/2 protein than normal developing lungs. Exposure to exogenous VEGF activated ERK 1/2 in normal developing lungs but not in hypoplastic lungs. Our results suggest that in hypoplastic lungs: 1) low VEGF signifies negative effects on vasculogenesis/angiogenesis and indicates altered endothelial-mesenchymal interactions; 2) increased ANG-1 protein may be required to maintain vessel integrity and quiescence; and 3) regulation of ERK 1/2 protein is affected in hypoplastic lungs. We speculate that extensive remodeling of blood vessels in hypoplastic lungs may occur to compensate for structurally and functionally defective vasculature.     

A prehistoric example of polydactyly from the Iron Age site of Simbusenga, Zambia

Human burials, dated AD 1100-1500, were examined from the Iron Age site of Simbusenga, located some 35 miles northwest of Victoria Falls in Zambia. Pedal polydactyly was discovered in the fragmentary remains of a young adult of indeterminate sex aged 14-25. The preaxial form of polydactyly is indicated with bilateral involvement of the first metatarsals. There is incomplete hypoplastic duplication of both first metatarsals with broad heads for the metatarsal-phalangeal joints. No digital malformations were found in the other seven individuals with feet and/or hands from the site. Several studies point to autosomal dominance for cases of isolated polydactyly, but inheritance and patterning of preaxial polydactyly are still incompletely understood. The condition is also found in conjunction with genetic malformation syndromes such as Acrocephalypolysyndactyly, Lambotte, Oro-facio-digital, and VATER. High frequencies of polydactyly are reported for African and African-American populations, but further analysis reveals that the bulk of previously reported cases of polydactyly are representative of the postaxial form as opposed to the preaxial expression seen here.     

Suprainguinal ectopic scrota of TS inbred rats

A new rat line (TS inbred rats) showing uni- or bilateral ectopic scrota in about 70% of the males was established. Ectopic scrota were elongated pouches of the thin muscle layer under the suprainguinal body skin, in which hypoplastic testes and epididymides were seen. Genetic analysis revealed that the ectopic scrotum was controlled by multiple genes. Groups of 5 normal, uni- and bilaterally affected rats were killed at 25 weeks of age. Histologically, ectopic testes of uni- and bilaterally affected rats showed arrest of spermatogenesis at the primary spermatocyte stage. Contralateral testes of unilaterally affected rats were normally descended and showed normal spermatogenesis. No abnormality was seen in the urinary system. Plasma concentrations of FSH were significantly elevated in bilaterally affected rats but plasma concentrations of testosterone and LH were unchanged in uni- and bilaterally affected rats. Pituitary contents of LH and FSH were significantly elevated in bilaterally affected rats. The endocrinological status of TS inbred rats was therefore similar to that of experimentally induced cryptorchid rats.