Combined Malformations Research Articles

Basal cell hamartoma and cellular naevus: an unusual combined malformation.

SUMMARY In this report are discussed three similar complex lesions which were composed of intermingled elements of a hamartomatous basal cell tumour and of a dermal cellular naevus. It appeared that some of the naevus cells arose directly from the basal cell strands in the deep portions of the hamartoma. This situation is contrasted with the coincidental origin of an aggressive basal cell epithelioma at the site of a dermal naevus. An instance of a dermal cellular naevus and an immediately adjacent syringoma is also described.

Cervicofacial vascular anomalies. II. Vascular malformations

Vascular malformations are the second major category of vascular anomalies. In contrast to vascular tumors, they are present at birth and grow commensurately with the child. Although the molecular mechanisms underlying the formation of these lesions remain unclear, lesions are known to result from abnormal development and morphogenesis. Histologic examination of vascular malformations shows no evidence of cellular proliferation, but rather progressive dilation of abnormal channels. Vascular malformations are designated according to their predominant channel type; they may be capillary, venous, lymphatic, arterial, and combined malformations. Malformations with an arterial component are rheologically fast-flow, whereas capillary, lymphatic, and venous malformations are slow-flow in nature. The morbidity of vascular malformations varies greatly both within and among the clinical subgroups cited above. This article describes the clinical presentation, diagnosis, and management of vascular malformations. The more frequently encountered clinical presentations involving the head and neck are highlighted.

An exceptional combined malformation: duplication of the urinary and intestinal tracts and the vulva (04-80CR)

The authors reported the surgical treatment of a 2-year-old girl with complete duplication of the kidney, ureter, bladder, urethra, and the vulva, associated with intestinal duplication and complete duplication of the appendix and colon. Congenital intestinal malrotation also concurred. After a series of preoperative examinations, exploratory operation including reduction of intestinal malrotation, fusion of bladder and colon, obliteration of the duplicated urethra, resection of the intestinal and appendiceal duplications, and cosmetic repair of the vulva was performed. Incontinence of urine and stool disappeared, and she had been followed up for 10 months until this report. Repeat voiding cystourethrography performed recently demonstrated a fused bladder and the disappearance of the duplicated urethra.

A novel syndrome of congenital lid and punctal anomalies, corneal and chorioretinal dystrophy

A 28-year old woman had an ocular syndrome consisting of congenital lid and punctal anomalies, and corneal and chorioretinal dystrophy without facial dysmorphism.These combined malformations of the ocular adnexae and both anterior and posterior ocular segments have not been previously described and appear to represent a novel syndrome. Direct sequencing of PAX6 and the DNA-binding domain of FOXC1 failed to detect a mutation.

Hereditary intraosseous vascular malformation of the craniofacial region: an apparently novel disorder.

Primary intraosseous vascular anomaly, previously called intraosseous hemangioma, is a very rare malformation that is usually seen in the vertebral column and in the skull. It is exclusively described in sporadic cases and no hereditary component has yet been reported. The most commonly affected bones in the skull are the mandible and the maxilla, and life-threatening bleeding after a simple tooth extraction is frequently observed. Here, we report two consanguineous families containing a total of four affected patients manifesting primary intraosseous vascular malformation (VMOS (vascular malformation osseous)) of the craniofacial region. The phenotypic expression is remarkably similar in both families. The characteristic findings include severe blood vessel expansions within the craniofacial bones and midline abnormalities such as diastasis recti, supraumbilical raphe, and hiatus hernia. Malformation is restricted to the mandibular and maxillary area in the prepubertal age, and rapid expansion starts after age 12 or 13. A 15-year follow-up of one of the patients demonstrated that the vascular malformation did not extend beyond the craniofacial region despite severe involvement of almost all bones in the skull. Detailed clinical and radiological evaluation provided neither evidence of soft-tissue involvement nor any sign of gross arterial, venous, or combined malformations, indicating that bone changes are a primary rather than a secondary effect due to any other vascular anomaly in the craniofacial region. An antibody against a universal proliferation marker, Ki-67, detected nonproliferative, single-layered endothelial cells, suggesting that this abnormality is a vascular malformation rather than a hemangioma. alpha-actin staining (antibody against perivascular tissue such as smooth muscle cells (SMCs) and/or pericytes) demonstrated that pathologic vessels lost their surrounding supportive tissues, as was previously seen in other types of vascular anomaly. Homozygosity mapping excluded the following loci and/or genes: multiple cutaneous venous malformation (VMCM1; gene, TIE2) on chromosome 9p21; venous malformation with glomus cells (VMGLOM) on chromosome 1p22-p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type 1 (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2-q21, 7p15-p13, and 3q35.2-q27, respectively. To the best of our knowledge, this is a new disorder, which we call hereditary intraosseous vascular malformation of the craniofacial region.

Male rats exposed to linuron in utero exhibit permanent changes in anogenital distance, nipple retention, and epididymal malformations that result in subsequent testicular atrophy.

Prenatal exposure to the herbicide linuron, a weak androgen receptor antagonist, has been shown to perturb androgen-dependent male rat reproductive development as evidenced by slight decreases in anogenital distance (AGD), increased retention of areolae/nipples, and induction of epididymal malformations in combination with testicular atrophy in the adult rat over dose levels ranging from 12.5 to 100 mg/kg/day. Studies were undertaken to determine whether linuron-mediated changes in AGD and nipple retention are permanent, whether linuron is a direct testicular toxicant, and if there was an association between areola/nipple retention and malformations. Pregnant rats were administered corn oil vehicle or linuron by gavage at 0 or 50 mg/kg/day (n = 8 controls, 20 treated) from gestation days 12 to 21. Male offspring were necropsied on postnatal days (PND) 35 and 56. Linuron-exposed male rats exhibited a significant (8%) decrease in AGD on PND 1 and a similar decrease was also observed on PND 56. Linuron-exposed male rats displayed an increase in areola retention on PND 13, as evidenced by 0.6 +/- 0.5 and 3.3 +/- 0.4 areolae per rat in the control and exposed groups, respectively. Male rats displayed a significant increase in nipple retention on PND 35 and 56 (collectively) of 0 +/- 0.5 and 1.7 +/- 0.3 nipples per rat in control and exposed groups, respectively. On PND 35, 4/51 rats (3/9 litters) from linuron-treated dams displayed enlarged testes in combination with malformed epididymides. Epididymal malformations were observed in 19/51 rats (6/9 litters) in the linuron-exposed dose group. On PND 56, grossly enlarged and edematous testes were seen in 16/56 linuron-exposed rats (6/9 litters). Epididymal lesions were observed in 23/58 rats (6/9 litters). Microscopically, all linuron-exposed animals that exhibited a testicular lesion on PND 56 also displayed an epididymal lesion. These lesions were not seen in control animals. Approximately 25 and 60% of the male offspring that had malformations of the epididymis and vas deferens did not exhibit either areolae on PND 13 or nipples at necropsy, respectively. These data indicate that in utero linuron exposure to 50 mg/kg/day results in permanent changes in AGD and nipple retention in male rats. Moreover, these findings indicate that linuron-induced testicular atrophy, which is observed in adult rats, is secondary to increased intratubular pressure resulting from obstruction of testicular fluid outflow subsequent to malformation of the epididymides. These data also suggest that although linuron-mediated retention of areolae on PND 13 and nipples at necropsy may be suggestive of altered testosterone-mediated reproductive development seen in adult rats, these endpoints are not predictive.

Vascular and neural malformations

The presentation of vascular and neural malformations in an understandable terminology permits accurate diagnosis, proper treatment, individualized prognosis, and also stimulates studies of pathogenesis. The descriptive classification includes: NF 1 and NF 2; hemangiomas, low- and high-flow vascular malformations, combined malformations, and hypertrophy; and syndromes such as, Parkes Weber, Klippel-Trénaunay, Maffuci's, and multiple dysplasia syndromes. Lymphatic malformations are abnormalities of lymphatic development. The list of treatment includes surgical and nonsurgical treatment. Not all vascular malformations can be successfully treated. Coping with NF is a challenge for both, affected individuals and health care professionals. NF is often associated with a myriad of anomalies that present a lot of problems for plastic surgery. In certain cases watchful waiting seems justified but not in cases of severe problems, giant growth, and local complications.

Zur Klassifikation vaskulärer Fehl- und Neubildungen

Vascular malformations and neoplasms are very common skin disorders, found in up to 5% of newborns. However, a clear distinction has to be made between proliferating vascular lesions and permanent malformations. An exact classification is also extremely useful, since many new specific diagnostic and therapeutic measures have been developed in recent years. True proliferating tumors are, for example, childhood hemangiomas, glomus tumors, granuloma pyogenicum, tufted angiomas, senile angiomas, and malignant vascular lesions. Vascular malformations can affect capillaries, veins or arteries, as well as lymphatic vessels. Arteriovenous shunts and combined malformations may also exist (Hamburg classification). Nevi flammei, nevi anaemici, hematolymphangiomas, angiokeratotic nevi, circumscribed venous-arterious malformations, and the blue-rubber-blebnevus-syndrome may either be infiltrating or circumscribed and are characterised by a persistence of the primitive vessel network. In contrast, other malformations involve various vascular trunks, showing vessel dilation or obstruction, often combined with changes in bone or soft tissue. Significant large vessel malformations are the Bockenheimer syndrome, the Klippel-Trenaunay syndrome and the Parkes-Weber syndrome. Combinations involving both large trunks and extravascular space such as the Klippel-Trenaunay syndrome also occur.

Vascular malformations: a review of 10 years' management in a university hospital

In order to gain insight into the management of patients with vascular malformations (VM) in the University Hospital Nijmegen in the past 10 years, 151 cases managed by different specialists were reviewed. To avoid the usual confusion in terminology, all recorded diagnoses were reclassified according to the biological classification of Mulliken. The sex distribution was equal; 79% of the malformations were diagnosed at birth or in the 1st year of life. The median time between presentation and consultation was 3 years. Sixty-two lymphatic, 26 venous, 24 capillary, 1 arterial, and 38 combined malformations (8 arteriovenous, 30 others) were found. The head and neck region was most frequently involved, followed by the lower and upper limbs and trunk. The pediatric surgeon was the most frequently consulted specialist. Confusing, mutually incompatible terminology and a wide variety of different diagnostic techniques and treatments had been used by the different specialists. To improve the management of patients with vascular malformations, the use of a uniform classification, an increase in basic investigations, and the development and evaluation of protocols for diagnosis and treatment by multidisciplinary teams are necessary.

Will α-Fetoprotein Analysis Be Useful in Detecting Fetal Anomalies in the First Trimester?

The purpose of this retrospective study was to determine if maternal serum (MSAFP) or amniotic fluid (AF-AFP) α-fetoprotein analysis might he useful in detecting fetal structural defects in the first trimester. During a 5-year period, 20 fetal anomalies were diagnosed at 11–13 weeks by transvaginal ultrasound scanning. A MSAFP sample was obtained in all 20 patients and 17 patients had AF-AFP results obtained by an early amniocentesis. Ten of 20 patients (50%) had elevated MSAFP levels, and 6 or 17 patients had elevated AF-AFP samples (35%). MSAFP was elevated in 4 of 5 cases of anencephaly (80%), in one fetus with the combined malformations of anencephaly and omphalocele, in one fetus with a large encephalocele, in 2 of 3 fetuses (67%) with an omphalocele, and in two cases of cystic hygroma with an abnormal karyotype. AF-AFP was elevated in 3 of 3 cases of anencephaly, in one fetus with the combined defects of anencephaly and omphalocele, in 1 of 3 cases (33%) of omphalocele, and in one fetus with an ence...

REVIEW

Disturbances of acrosomal development and function significantly impair the fertilizing capacity of spermatozoa. Therefore, evaluation of acrosomal morphology and function is of particular importance in the diagnostic testing of male infertility. Acrosomal disturbances include either specific defects showing a complete absence of certain acrosomal structures or various acrosomal malformations in combination with nuclear or flagellar defects which indicate acquired testicular disorders. As examples of specific acrosomal defects, the syndrome of round-headed spermatozoa (globozoospermia), the crater defect syndrome and the syndrome of decapitated spermatozoa are discussed. In addition to disturbances of acrosomal morphology, the assessment of acrosomal proteinase activity and the acrosome reaction as a method of evaluating impaired acrosomal functions is discussed. Clinical examples demonstrate the importance of these sperm function tests in the fertility testing of infertile men.

Malformations of the spinal cord in 53 patients with spina bifida studied by magnetic resonance imaging

The incidence of associated malformations of the hindbrain and spinal cord in patients with spina bifida was investigated by a clinical and magnetic resonance study. The incidence of these malformations in combination with spina bifida was 49/53 (92.5%). Fifty-tree children born with spina bifida aperta (40 patients) or spina bifida occulta (13 patients) formed the study group. The incidence of the various malformations were: Chiari malformations, type I, 10/53 (19%), and type II, 20/53 (38%); syringomyelia, 13/53 (24.5%); hydromyelia 4/53 (7.5%); tethered cord malformation, 35/53 (66%); diastematomyelia 2/53 (4%). Thirty-seven of the 49 patients with associated malformations had no clinical signs at the time of our study. The results point to the fact that in the pediatric age group, associated spinal defects often remain asymptomatic.

Sonographische Diagnostik fetaler Harntraktanomalien - Inzidenz, Therapie und Verlauf

561 severe foetal malformations were seen from 1975 to 1986 in a total of 17,057 births (3.3%). The urogenital tract was involved in 164 cases only (1.0%). The proportion of malformations of the urinary tract was 29% of all observed anomalies. In 31% of the cases (51 of 164) there were isolated malformations, and in 20% (33 of 164) combined malformations of the urinary tract. 58% (96 of 164) of the urinary tract anomalies definitely belonged to syndromes (e.g. Potter's syndrome). Of 68 newborns with correctable urogenital changes, 42 were diagnosed as obstructive uropathy, 7 of which with urethral valves. A highly critical view is taken of the possibilities of intrauterine therapy in obstructive uropathies.

Intramedullary vascular lesions in the high cervical region: transoral and dorsal surgical approach. Two case reports

Intramedullary vascular malformations in the high cervical region are extremely rare. Two young adult patients with vascular lesions at the level C 2 and 3, and C 2-4 are reported. In one patient selective spinal angiography revealed a combined malformation with a ventral intramedullary arteriovenous angioma and a premedullary aneurysm. This malformation was approached and removed transorally after spondylectomy of C 2. In the second patient MRI and selective angiography showed an intramedullary hemangioblastoma extending from C 2-C 4. After embolization, this lesion was surgically removed via a dorsal approach. Both patients suffered from severe neurological deficits preoperatively. MRI and selective angiography showed the exact locations of the tumors within the spinal cord and indicated a transoral approach in one case and a dorsal approach in the other. After complete obliteration and removal of the lesions, the patients showed no neurological deficits and returned to their previous professions.

Desmoplastic trichoepithelioma and intradermal nevus: A combined malformation

We studied 13 desmoplastic trichoepitheliomas associated with intradermal nevi. Ten intradermal nevi were found among 76 new cases of desmoplastic trichoepithelioma (13%); three additional examples of the combined malformation were seen in consultation. Clinically, desmoplastic trichoepithelioma associated with an intradermal nevus was typically a small, firm or hard, sometimes annular, nodule on the face, particularly the cheek, of a relatively young woman. Microscopically, the combined malformation contained narrow strands of basaloid cells and keratinous cysts in a desmoplastic stroma, intimately mixed with intradermal nests of nevocytes. Melanocytic nevi have been associated with epidermal hyperplasia resembling seborrheic keratoses, follicular cysts, trichostasis spinulosa, syringomas, basal cell carcinomas, and hair follicle formation on the soles. The frequency of the occurrence of intradermal nevus with desmoplastic trichoepithelioma and the close anatomic association of the two elements may indicate that this combined malformation is another example of epithelial induction by melanocytic nevi.

Hypospadias in adulthood

Hypospadias should not be considered as a congenital local defect only in the development of the urethra; the problem extends beyond the local malformation to the physical and intellectual development of the patient. It would also be incorrect to regard the problem of hypospadias as settled if the operative correction is performed, since mostly with puberty, but partly also later, changes may occur in general but particularly also in sexual development, placing a difficult burden on the hypospadias sufferer. The discussion of hypospadias problems in adults therefore embraces a subject that reaches far beyond operative correction into areas of miction, fertility and sexuality and therefore represents a wide complex of physical and mental problems. Above all, the question should be examined what quality of life a hypospadias patient can expect in the future after correction of this congenital malformation in infancy. The following factors describing the special circumstances of living after hypospadias operation, appear to be worthy of discussion: 1. The physical situation which includes the ability of erection, miction, fertility, the cosmetic aspect of the outer genital organ and potential consequences of combined malformations. The mental or "psychic" situation, which reaches into sexual life, partnership and profession. Only a few clinical departments concerned with the primary correction of hypospadias in infancy have controlled a group of patients up to adult age. For these reasons we considered it necessary to collect as far as possible the experiences mentioned in the literature and to combine them with our own observations to arrive at corresponding conclusions.

The challenge of upper airway obstruction in pediatric intensive care.

Over a 5-year period, 75 patients were admitted to a pediatric intensive care unit because of acute upper airway obstruction (AUAO). Congenital abnormalities were demonstrated in 25 children; 9 of them died secondary to severe combined malformations or major central nervous system dysfunction. Acquired AUAOs were seen in 50 patients; 1 died in brain death secondary to anoxia. Obstructions were observed at all levels of the airways from the nose to the carina. In 28% of the patients, AUAO had remained undiagnosed until admission for complications such as acute respiratory failure, cardiac arrest, coma, seizures. With early diagnosis and prompt release of the obstruction the prognosis is good unless severe congenital abnormalities or major central nervous system damage are associated.

Prenatal diagnosis and postnatal course in abnormalities of the kidneys and urinary tract

The authors' own experiences concerning the prenatal diagnosis and postnatal course in 26 foetuses with anomalies of the urinary tract are reported. The malformations observed can be separated into five groups which can also be distinguished sonographically: Urinary tract malformations of poor prognosis, Unilateral cystic kidneys. Hydronephroses, Urinary tract malformations with ascites, Urinary tract malformations in combination with other anomalies of poor prognosis. Sonographic differentiation of the multicystic kidney (Potter type IIA) from the hydronephrosis is usually possible. The recognition of cystic renal dysplasia in urinary tract obstructions (Potter type IV) and the differentiation of renal hypoplasia from renal agenesis is difficult. The dilatation of the urinary system has to be generally regarded as an unspecific symptom, the cause of which can be finally clarified only in the postnatal period. Prenatal invasive diagnostic procedures were carried out only in two foetuses. A concomitant anhydramnios was always associated with a poor prognosis. In the case of unilateral of bilateral dilatation of the urinary tract with normal or slightly diminished amniotic fluid volume, induction of labour or prenatal intervention for drainage in utero was not indicated. The prognosis was infaust in 15 foetuses. One infant died of an unknown cause. Out of 10 surviving infants, six were successfully operated on, in three the dilatation of the urinary tract resolved spontaneously, and one child with prune belly-syndrome has to be catheterised daily.

Antenatal diagnosis of congenital anomalies.

Twelve neonates with surgical malformation diagnosed antenatally by ultrasound tomography (UST) with or without foetography were reported. Clinical diagnosis of these 12 cases were: Omphalocele 1, cervical teratoma 1, pyloric atresia 1, duodenal atresia 6, high jejunal atresia 2 and hydronephrosis 1. Three of these 12 deteriorated because of respiratory difficulty before the surgical intervention could be attempted. Operations were performed on the remaining 9 and 6 of them are surviving. The main causes of these postoperative deaths were respiratory complications and combined malformations. UST can detect numerous surgical malformations of the foetus. Antenatal diagnosis of the nature of a malformation may enable corrective surgery to be carried out with minor delay after birth, and good results can be obtained.

Familial Renal Agenesis and Urogenital Malformations

A seminal vesicle cyst was found in a 30-year-old man with ipsilateral renal agenesis. His sister had embryologically analogous malformations--Gartner duct cyst, bicornuate uterus and renal agenesis. This seems to be the first reported familial occurrence of these combined malformations. The embryogenesis is reviewed and the diagnostic procedure and treatment are discussed.