Greenberg dysplasia (hydrops–ectopic calcification–moth‐eaten skeletal dysplasia): Prenatal ultrasound diagnosis and review of literature

A second pregnancy of young, nonconsanguineous parents of Macedonian ethnic origin was examined by ultrasound. Polyhydramnios and hydrops fetalis were found as well as severe short limb, short stature, and cystic hygroma of the neck. An artificial abortion was performed at the age of 23 weeks. The radiological features included moth‐eaten severely shortened long bones and ectopic calcifications of long bones, vertebral column, ribs, pelvis, larynx, trachea. In addition, the fetus had large head with depressed nasal bridge, severe platyspondyly, and short barrel‐shaped trunk. Light microscopy demonstrated lack of chondrocyte columns and disorganization of the cartilaginous architecture. This is the seventh reported case of this rare form of lethal skeletal dysplasia. © 2002 Wiley‐Liss, Inc.     

Prenatal diagnosis of Meckel syndrome: case reports and literature review

We report on 2 couples at risk to have Meckel syndrome (MS) offspring. Three pregnancies were monitored by ultrasonography and alpha-fetoprotein (AFP) assay in midtrimester. Of the 2 involving an affected fetus, one was thought to be unaffected. A literature survey was undertaken. Sources of error seem to lie in the heterogeneity of clinical manifestations and the variable onset and rate of progression of clinical components of MS and limitations in ultrasonographic resolution inherent in the scanner or due to the associated oligohydramnios. The following observations/suggestions are made concerning the prenatal diagnosis of MS: 1) Utilize as many tests as are available. 2) Amniotic fluid AFP is more likely to show significant elevation than serum AFP. 3) Ultrasonography should concentrate on presence of oligohydramnios, small head diameter, cystic mass at the occiput, large kidneys, and absent bladder. 4) Use serial AFP and sonographic examination if findings are initially normal or equivocal.     

Prenatal presentation and diagnosis of Baraitser‐Winter syndrome using exome sequencing

Baraitser‐Winter cerebrofrontofacial syndrome (BWCFF) is a rare autosomal dominant developmental disorder associated with missense mutations in the genes ACTB or ACTG1. The classic presentation of BWCFF is discerned by the combination of unique craniofacial characteristics including ocular coloboma, intellectual disability, and hypertelorism. Congenital contractures and organ malformations are often present, including structural defects in the brain, heart, renal, and musculoskeletal system. However, there is limited documentation regarding its prenatal presentation that may encourage healthcare providers to be aware of this disorder when presented throughout pregnancy. Herein we describe a case of a pregnancy with large cystic hygroma and omphalocele. Whole exome sequencing (WES) was performed and a de novo, heterozygous, likely pathogenic mutation in ACTB was detected, c.1004G>A (p.Arg335His), conferring a diagnosis of BWCFF.     

Uruguay facio‐cardio‐musculo‐skeletal syndrome: A novel X‐linked recessive disorder

We report on three male patients from a single family with a brachyturricephaly, “pugilistic” facial appearance, a muffled voice, cardiomyopathy, muscular hypertrophy, broad hands, wide feet with progressive pes cavus deformities, dislocation of toes, variable congenital hip dislocation, and scoliosis. Three other males in the family, now deceased from cardiac disease, appear to have had the same disorder. The mother of the propositus has milder signs of the syndrome. All affected males are related through the maternal line. These cases represent an apparently previously undescribed X‐linked recessive syndrome. Am. J. Med. Genet. 95:247–265, 2000.     

Piepkorn type of osteochondrodysplasia: Defining the severe end of FLNB‐related skeletal disorders in three fetuses and a 106‐year‐old exhibit

The Piepkorn type of lethal osteochondrodysplasia (POCD) is a rare and lethal dwarfing condition. Four cases have been reported to date. The characteristic features are distinctly shortened “flipper‐like” limbs, polysyndactyly, excessive underossification, especially of the limb bones and vertebrae, and large (giant) chondrocytes in the cartilaginous bone primordia. These characteristics allowed the diagnosis of Piepkorn type of osteochondrodysplasia in four new cases, three fetuses of 15 to 22 weeks and one 106‐year‐old museum exhibit. Piepkorn type of osteochondrodysplasia has been assigned to the giant cell chondrodysplasias such as atelosteogenesis type 1 (AO1) and boomerang dysplasia (BD). Analysis of the Filamin B gene in 3p14.3, which is associated with these disorders, allowed the identification of the first FLNB mutations in Piepkorn type of osteochondrodysplasia. The heterozygous missense mutations, found in the three fetuses, were located in exons 28 and 29, encoding the immunoglobulin‐like repeat region R15, one of three mutational hot spots in dominant FLNB‐related skeletal disorders. Direct preparations and alcian blue staining revealed single upper and lower arm and leg bone primordia, preaxial oligodactyly, and polysyndactyly with complete fusion and doubling of the middle and end phalanges II–V to produce eight distal finger rays. Considering the unique clinical features and the extent of underossification, Piepkorn type of osteochondrodysplasia can be regarded as a distinct entity within the AO1‐BD‐POCD continuum.     

Prenatal diagnosis of the prune belly syndrome

A male fetus with prune belly syndrome was diagnosed by ultrasound at 30 weeks of gestation. The diagnosis was confirmed after birth.     

Walker-Warburg syndrome: Report of three affected sibs

Walker-Warburg syndrome (WWS) is a lethal, autosomal recessive disorder characterized by Type II lissencephaly, retinal malformation, cerebellar malformation, and congenital muscular dystrophy. We report on 3 sibs with WWS born to a consanguineous couple. The fetal hydrocephalus associated with this syndrome, while not consistent or necessary for diagnosis, is the key manifestation for its prenatal detection. These sibs illustrate the importance of a careful search for associated malformation(s) in a fetus or newborn infant with hydrocephalus and the potential pitfalls of accurate genetic risk estimation in families of such propositi. © 1994 Wiley-Liss, Inc.     

A novel biallelic loss‐of‐function mutation in TMCO1 gene confirming and expanding the phenotype spectrum of cerebro‐facio‐thoracic dysplasia

The main clinical features of cerebro‐facio‐thoracic dysplasia (CFTD) syndrome, which were described over four decades ago, include facial dysmorphism, multiple malformations of the vertebrae and ribs, and intellectual disability. Recently, a TMCO1 gene mutation was shown to be responsible for an autosomal recessive CFTD syndrome characterized by craniofacial dysmorphism, skeletal anomalies, and intellectual disability. In the current report, we describe two members of a consanguineous family from an Arab community in Israel who were clinically diagnosed as suffering from craniofacial dysmorphism, skeletal anomalies, intellectual disability, and epilepsy. Both affected siblings had behavioral difficulties such as anxiety and emotional instability with impulsive behaviors. Whole‐exome sequencing revealed a homozygous stop‐gain mutation NM_019026.4: c.616C > T; p.(Arg206*) in exon 6 of the TMCO1 gene. Bioinformatics analysis suggested a structural model for the TMCO1 protein and its homologues. The clinical features of our patients were compared with those of the only other five studies available in the literature. We conclude that this mutation in the TMCO1 gene is responsible for the various clinical manifestations of CFTD syndrome exhibited by the patients studied that expand the phenotypic spectrum of the disease to include epilepsy as a characteristic feature of this syndrome.     

栅状肌纤维母细胞瘤3例报道及文献复习

目的：观察栅状肌纤维母细胞瘤的临床病理特征，探索该肿瘤的组织来源及石棉样纤维的性质和来源。方法：对３ 例栅状肌纤维母细胞瘤进行组织形态学和免疫组织化学研究，结合文献对本病的诊断标准、鉴别要点及组织来源进行探讨。结果：栅状肌纤维母细胞瘤的组织学特点为梭形肿瘤细胞呈交叉束状、栅栏状排列，间质内有较多出血、散在的肥大细胞，肿瘤中出现石棉样纤维。免疫组化见肿瘤细胞及石棉样纤维星芒状突起中ａｃｔｉｎ、ｖｉｍｅｎｔｉｎ 呈阳性表达，ｄｅｓｍｉｎ、Ｓ１００ 、ＦａｃｔｏｒⅧ、ｃｙｔｏｋｅｒａｔｉｎ 呈阴性表达。结论：栅状肌纤维母细胞瘤是一种具有独特临床病理特征的肌纤维母细胞瘤，该肿瘤来源于肌纤维母细胞或特殊平滑肌细胞亚型。石棉样纤维中心为血管周围胶原的变性，星芒状纤维为增殖的肌纤维母细胞突出的中间丝和微丝。     

Prenatal diagnosis of retinal nonattachment in the Walker-Warburg syndrome

We report on the prenatal ultrasonographic diagnosis of Walker-Warburg syndrome based on cerebral and ocular findings. The ultrasound study done at 37 weeks gestation documented hydrocephalus and retinal nonattachment consistent with this syndrome. The ability to detect retinal nonattachment prenatally may have implications for the prenatal diagnosis of other conditions which have early retinal nonattachment as one of their findings. However, it is uncertain how early in pregnancy this defect can be detected. © 1995 Wiley-Liss, Inc.     

Ring chromosome 6 in three fetuses: case reports, literature review, and implications for prenatal diagnosis

Prenatal and postnatal findings in three fetuses with a ring chromosome 6 are presented, and the literature of this rare cytogenetic disorder is reviewed. The described fetuses illustrate the broad spectrum of the clinical manifestation of ring chromosome 6. In one fetus, the disorder was diagnosed incidentally by a routine amniocentesis due to advanced maternal age. The other two fetuses were hydrocephalic and had other congenital anomalies. Remarkably, the ring chromosome 6 tends to disappear in cultured amniotic fluid cells; karyotyping revealed complete or nearly complete monosomy 6. In contrast, the ring was preserved in high proportions of fetal leukocytes. Postnatal growth retardation is the only consistent finding of this chromosomal disorder. Maternal age is not significantly above average. An additional review of 20 literature cases revealed a striking tendency to hydrocephalus, either due to deficient brain growth or secondary to an aqueductal stenosis. Children with hydrocephalus and ring chromosme 6 tend to display facial dysmorphism and may have additional malformations, growth failure, eye anomalies, and seizures. In contrast, there are two reports on children with a ring chromosome 6 who had short stature, normal appearance, and a normal or almost-normal psychomotor development. In such patients at the mild end of the clinical spectrum, the phenotype is basically restricted to what Kosztolányi. [1987: Hum Genet 75:174-179] delineated as "ring syndrome," comprising "severe growth failure without major malformations, without a specific deletion syndrome, with only a few or no minor anomalies, and mild to moderate mental retardation." This "ring syndrome" is considered to occur independently of the autosome involved in the ring formation. The overall impression from our cases and from the literature review of cases with ring chromosome 6 is that the karyotype-genotype correlation is poor. This makes prognostic counseling of parents difficult and unsatisfactory. Serial targeted ultrasound examinations, especially of the brain, are decisive factors in elucidating the prognosis.     

Pituicytoma: Report of three cases with review of literature

Pituicytoma is a rare low-grade tumor (WHO Grade I) of pituicytes involving the sellar–suprasellar region, and originating from the specialized glial cells of the neurohypophysis. Clinically and radiologically, they closely mimic pituitary adenoma or meningioma. Diagnosis requires histopathological examination of the resected tissue. This uncommon glial neoplasm is a rarity, with only 57 cases reported in the literature so far. We report three cases of pituicytoma (aged between 7 and 24 years) presenting with reduced vision, headache and features of hypercortisolism in one case. Radiologically, these lesions mimicked meningioma, hypothalamic chiasmatic glioma and pituitary microadenoma, respectively. The second case is a 7-year-old girl, the youngest case on record. Since this tumor is uncommon, it is frequently misdiagnosed. Awareness of this entity is essential for planning management and treatment. We present a brief review of all cases reported in the medical literature, and describe the clinical symptomatology, associated endocrinological abnormalities, imaging characteristics, behavior and outcome.