Fryns syndrome: report on 8 new cases

The name Fryns syndrome was given to a new variable multiple congenital anomaly syndrome, almost always lethal, described in 1978, and now known to be autosomal recessive. Since that date, 20 patients have been reported in the literature. We describe 8 new cases, 6 of which were diagnosed in a series of 112,276 consecutive births (livebirths and perinatal deaths). The prevalence of this syndrome can be estimated to be around 0.7 per 10,000 births. These new cases confirm that the most frequent anomalies are diaphragmatic defects, lung hypoplasia, cleft lip and palate (often bilateral), cardiac defects (septal defects and aortic arch anomalies), renal cysts (type II, III or IV), urinary tract malformations, and distal limb hypoplasia. Most patients also have hypoplastic external genitalia and anomalies of internal genitalia (bifid or hypoplastic uterus, immature testes). The digestive tract is also often abnormal: duodenal atresia, pyloric hyperplasia, malrotation and common mesentery are present in half of the patients. When the brain was examined, more than half were abnormal (Dandy-Walker anomaly and agenesis of corpus callosum). A few patients demonstrated cloudy cornea. We examined the eyes of three patients histologically: two of them showed retinal dysplasia with rosettes and gliosis of the retina, thickness of posterior capsula of lens and irregularities of the Bowman membrane. Four of our cases were diagnosed prenatally between 24 and 27 weeks. It is to be expected that prenatal diagnosis will be made often and earlier in the future, as the spectrum of anomalies of the Fryns syndrome can easily be evidenced by sonography.     

Manitoba Oculotrichoanal (MOTA) syndrome: report of eight new cases

The Manitoba Oculotrichoanal (MOTA) syndrome was initially described by Marles et al. [1992; Am J Med Genet 42: 793-799] in Aboriginal patients of the Island Lake region of Northern Manitoba. Characteristic findings in affected patients included unilateral upper eyelid coloboma or cryptophthalmus with ipsilateral aberrant anterior hairline pattern and anal anomalies. We describe here seven new patients of the same extended kindred of Cree/Ojibway ethnicity of the Island Lake region and an eighth patient of Caucasian Dutch parents with clinical findings consistent with the diagnosis of MOTA syndrome. Two of the patients have bilateral, instead of unilateral, abnormal anterior hairline patterns. Omphalocele, a feature previously not identified, is present in three of them. The most consistent features appear to be hypertelorism and a broad or notched tip of the nose. Due to the obvious clinical overlap with Fraser syndrome, FRAS1 gene was screened in two of the affected and no mutation was found [Slavotinek et al., submitted].     

Meier-Gorlin syndrome: report of eight additional cases and review

The Meier-Gorlin syndrome or ear, patella, short stature syndrome (MIM 224690) is a rare autosomal recessive disorder, characterized by the association of bilateral microtia, aplasia/hypoplasia of the patellae, and severe pre- and postnatal growth retardation. Twenty-one cases have been reported in literature thus far. Here we report on eight patients from seven families and compare them with previously described cases. One of the present cases had previously undescribed genital anomalies. There is a difference in facial characteristics between patients reported in early infancy and those described at older age; follow-up of patients is needed to substantiate this changing facial phenotype. We recommend radiographic survey of the patellae in patients at older age to investigate the weight of absent or hypoplastic patellae in the diagnosis of the syndrome.     

Fryns syndrome

We report on a premature female infant with Fryns syndrome who had several less commonly reported anomalies. She had bilateral posterior eventration of the hemidiaphragms instead of the usual diaphragmatic defects with visceral herniation into the chest cavity. She also had a unilateral cleft lip, camptodactyly, duodenal atresia, tracheomalacia, bronchomalacia, and Tetralogy of Fallot. © 1993 Wiley-Liss, Inc.     

Fryns syndrome: A new variable multiple congenital anomaly (MCA) syndrome

We report a brother and sister who died neonatally with a distinctive but variable multiple congenital anomaly (MCA) syndrome. Anomalies in both included similar facial changes, cleft palate, distal digital hypoplasia, lung hypoplasia, and urogenital abnormalities. They were discordant for cleft lip, diaphragmatic hernia, and Dandy-Walker anomaly. These sibs resemble three recently reported stillborn children and support the existence of a “new” autosomal recessive MCA syndrome with variable expressivity.     

A case of Fryns syndrome.

A case of Fryns syndrome is presented. Characteristic features of this lethal autosomal recessive disorder include corneal clouding, camptodactyly with hypoplastic nails, and abnormalities of the diaphragm.     

Anophthalmia-microphthalmia-oblique clefting syndrome: Confirmation of the Fryns anophthalmia syndrome

We describe a patient with bilateral extreme microphthalmia with bilateral congenital glaucoma, bilateral medial oblique facial cleft ending in lid colobomas, bilateral stenosis of the choanae, bifid uvula, frontal encephalocele, and premature craniosynostosis. The cause is unknown, but the phenotype resembles the Fryns anophthalmia-plus syndrome, which may be a recessive trait, although intrauterine environmental factors cannot be excluded. Am. J. Med. Genet. 73:36–40, 1997. © 1997 Wiley-Liss, Inc.     

Splenogonadal fusion limb defect syndrome: report of five new cases and review.

Splenogonadal fusion (SGF) is a rare congenital malformation in which the spleen is abnormally connected to the gonad. SGF may occur as an isolated condition or may be associated with other malformations, especially with terminal limb defects in what is called splenogonadal fusion limb defect (SGFLD) syndrome. In this article, we report on 5 new cases of SGFLD and we review the 25 cases reported since 1889. Most cases reviewed here have a combination of severe limb and oro-mandibular defects, suggesting that SGFLD may be related to the broader group of Hanhart complex. In addition, several cases have limb malformations and facial anomalies, which suggest that SGFLD overlaps with both femur-fibula-ulna dysostosis and femoral-facial syndrome. The hypothesis of a vascular disruptive event, occurring between the 5th and the 7th weeks of gestation, could explain the limb defects, the mandibular hypoplasia, and the fusion of the spleen to the gonad observed in SGFLD. However, this heterogenous and polytopic condition could also be the consequence of a primary field defect. All the cases to date reported have been sporadic and the recurrence risk is probably low. However, a recent case of Roberts syndrome with SGF was reported that suggests careful examination of chromosomal status.     

Skeletal manifestations in Fryns syndrome

We report on a female baby with Fryns syndrome who died soon after birth. The patient had short limbs, coarse face, hypoplastic lungs, diaphragmatic hernia, and acral hypoplasia. Literature review disclosed varying degrees of skeletal manifestations in Fryns syndrome; short limbs may be a component of Fryns syndrome. © 1995 Wiley-Liss, Inc.     

Hodgkin's disease variant of Richter's syndrome. Report of eight cases.

Large cell lymphoma associated with chronic lymphocytic leukemia (CLL)--Richter's syndrome--is a well-recognized entity. Rarely, Hodgkin's or "Hodgkin's-like" lymphoma associated with CLL has been reported. The authors present the clinicopathologic findings in eight cases of well-documented CLL in which solid tumors with histologic and immunostaining features of Hodgkin's disease subsequently developed. The histologic patterns observed in these tumors included nodular sclerosing (four cases) and mixed cellularity (four cases). In all eight cases, diagnostic Reed-Sternberg cells stained strongly with antibody to Leu-M1/CD15 but showed no reactivity with antibody to leukocyte common antigen (LCA/CD45). Survival ranged from 2 months to more than 8 years, with a 50% cumulative survival of 12 months; this is in contrast to the 2- to 4-month survival that typifies non-Hodgkin's Richter's syndrome. Therefore, it is important to recognize the Hodgkin's subgroup of lymphomatous CLL transformation.     

Ovarian pregnancy and operative laparoscopy: report of eight cases

We report a series of eight cases of ovarian pregnancy treated by operative laparoscopy during the last 12 years. This rare ectopic pregnancy (2.6% of all extra-uterine pregnancies in our experience) is difficult to diagnose prior to surgery. Earlier diagnosis is now possible, owing to the availability of highly specific radioimmunoassay for human chorionic gonadotrophin and the development of transvaginal ultrasonography. Primary ovarian pregnancy is distinguished by some authors from distal tubal pregnancy, in which a secondary ovarian implantation is possible. The therapy is surgical and currently more conservative than in the past, because of improvement in operative laparoscopy. Laparoscopy allows a short hospital stay, less physical stress and a favourable cost-benefit ratio. Moreover, its low risk of adhesion formation is important with regard to reproductive prognosis: in the light of this, since the patients are generally young and desire future childbearing, laparoscopy may be the treatment of choice.      

Mesotheliomas with small cell features: report of eight cases

Mesotheliomas with small cell morphology are rare and only one study of such cases has been published. As a result of their rare occurrence, some investigators have cast doubt on the existence of such a histologic variant of mesothelioma. This investigator reports a series of eight cases of epithelioid mesothelioma with small cell features, all of which originated in the pleura. Seven of the patients were men and one was a woman. Four patients had a history of asbestos exposure. Histologically, four of the mesotheliomas were epithelioid and four biphasic. The proportion of small cells seen in these cases constituted 80 to 100% of the tumor included in the biopsy material and 15 to 20% of the tumor present in the pneumonectomy specimens. Immunoreactivity for calretinin, keratin 5/6, keratin 7, pan-keratin, WT1, podoplanin, and mesothelin was seen in all cases tested for these markers. All of the cases were negative for MOC-31, Ber-EP4, CEA, CD15, TAG-72, TTF-1, chromogranin A, synaptophysin, CD99, and desmin. The mean survival of the six patients for whom this information was available was 8.2 months. It is important for pathologists to be aware that mesotheliomas can present small cell features and, because of this, they can be confused with other malignancies that can exhibit similar morphology. The value of immunohistochemistry in the differential diagnosis of these tumors is discussed.     

Filippi syndrome: report of three additional cases.

Filippi syndrome is an autosomal recessive condition characterized by variable soft tissue syndactyly of the fingers and toes, microcephaly, pre- and postnatal growth retardation, mildly abnormal craniofacial appearance, and mental retardation. We report on three unrelated individuals with Filippi syndrome. All have microcephaly, minor facial anomalies, variable syndactyly of digits, growth impairment, and developmental delay. One patient also has polydactyly, which has not been reported previously in the Filippi syndrome.     

Smith-Magenis syndrome: a new contiguous gene syndrome. Report of three new cases.

Interstitial deletion of the short arm of chromosome 17 was detected in three patients. They all had a similar phenotype with mental retardation, behavioural problems, facial dysmorphism, brachycephaly, a broad face with a flat midface, and short and broad hands. All three cases were ascertained over a six month period by two neuropaediatricians aware of this specific anomaly, which suggests that this microdeletion is not particularly rare. Comparison of the clinical and cytogenetic findings in a total of 24 patients allows a new contiguous gene syndrome to be defined that only high resolution analysis can detect. In two cases, molecular analysis confirmed the cytogenetic results. The Charcot-Marie-Tooth type Ia gene has recently been localised to the 17p11.2 sub-band.     

The clinical spectrum of the Fraser syndrome: report of three new cases and review.

Three new cases of the Fraser syndrome are presented and 68 published cases are reviewed. A quantitative estimate of the frequency of clinical manifestations is given. Craniofacial abnormalities were reported in all patients, cryptophthalmos in 93%, and syndactyly in 54%. Abnormalities of the ears, nose, genitalia, and urinary system were reported in 44%, 37%, 49%, and 37% of cases respectively. This variability should be taken into account when attempting prenatal diagnosis; a combination of ultrasound and fetoscopy should provide the best approach. Of the reported cases 26% were stillborn and 19% died in the first year of life. Renal and pulmonary malformations were associated with early death.     

Kaufman oculocerebrofacial syndrome: report of two new cases and further delineation

Figuera LE, García-Cruz D, Ramírez-Dueñas ML, Rivera-Robles V, Cantù JM. Kaufman oculocerebrofacial syndrome: report of two new cases and further delineation.
Clin Genet 1993: 44: 98–101. © Munksgaard, 1993
Two unrelated Mexican girls, aged 14 months and 6 years respectively, with Kaufman oculocerebrofacial syndrome, are reported. Both showed psychomotor retardation, microcephaly, blepharophimosis and delayed growth as the main features; the infant also presented preauricular tags and large clitoris. Comparative analysis with previous cases reveals a heterogeneous syndrome in which the micro-brachycephaly, the mongoloid slanted eyes with different anomalies, the micrognathia and the neonatal respiratory distress are the most typical characteristics of this mental retardation syndrome.