Biomedical subjects
Publications and source records attributed to H V Toriello.
We report on a child we believe may have the same condition described in five children by Burn et al., in 1992 (Clin Dysmorphol 1:137-144). Component manifestations include choanal atresia, cardiac defects, prominent ears, hearing loss, and minor facial anomalies. Our patient also has rather significant short stature, thus adding to the variable phenotype of this condition.
Explore the source record for details and available documents.
Explore the source record for details and available documents.
We report on a patient born to consanguineous parents and presenting with pseudopapilledema, mixed hearing loss, and minor facial and limb anomalies. To our knowledge, there is just one similar description of this syndrome in three members of a Brazilian kindred whose parents were also consanguineous, suggesting autosomal recessive inheritance. We compare the findings of our patient with these previous reported cases and discuss the differential diagnoses of this new syndrome, which we suggest be named the acro-oto-ocular syndrome.
Three unrelated infants presented with radiographic punctate calcifications, nasal hypoplasia, and abnormalities of the spine. Additional anomalies included cupped ears in 2 patients and one each with Dandy-Walker malformation with hydrocephaly, congenital cataracts, and peripheral pulmonary artery stenosis. The mothers of these 3 patients had chronic conditions associated with intestinal malabsorption requiring total parenteral nutrition for varying periods of time. The underlying causes of malabsorption were celiac disease, short bowel syndrome secondary to surgical resection, and jejuno-ileal bypass, respectively. Bleeding diathesis occurred in one mother requiring vitamin K supplementation during the second and third trimesters of pregnancy. We speculate that the chondrodysplasia punctata and other abnormalities in these children were caused by an acquired maternal vitamin K deficiency manifested during early pregnancy. However, the involvement of other vitamin deficiencies cannot be excluded. Thus, vitamin K deficiency of the embryo secondary to maternal malabsorption appears to be a third vitamin K-related mechanism leading to chondrodysplasia punctata in addition to warfarin embryopathy and epoxide reductase deficiency (pseudo-warfarin embryopathy).
We describe 13 unrelated children with abnormalities of somatic growth, face, brain, and connective tissue including vasculature. Although the condition in these children falls under the general group of disorders known as cutis marmorata telangiectatica congenita (CMTC), the constellation of abnormalities appears to constitute a distinct and easily recognizable phenotype within this general group. In contrast to most children reported with CMTC, children in this subgroup have a high risk for neurologic abnormalities, including developmental delay, mental retardation, megalencephaly, and hydrocephalus. Early recognition of this condition is important for appropriate surveillance for known complications and parental counseling.
The oral-facial-digital syndromes (OFDS) have in common minor facial and oral anomalies (including tongue lobulation and/ or hamartomas, accessory frenula, and alveolar anomalies) and variable digital defects such as polydactyly. The classification based on the presence of additional findings [Toriello, 1988, 1993] is not perfect, as many reported examples of a particular OFDS have some other condition. Here we describe six children, all diagnosed as having OFDS IV (OFDS with tibial defects), whose manifestations illustrate the apparent genetic heterogeneity.
Congenital pulmonary lymphangiectasis is a rare anomaly that is causally heterogeneous. It can occur as either an isolated finding or one manifestation of several multiple congenital anomaly syndromes. We describe a child with congenital pulmonary lymphangiectasis and the anomalies who likely has a provisionally unique condition.
Explore the source record for details and available documents.
Ehlers-Danlos syndrome (EDS) is a genetically and pathogenetically heterogeneous group of disorders of which at least 11 types have been described. All are connective tissue disorders characterized by defects of the skin, ligaments and blood vessels with the clinical spectrum ranging from innocuous findings to lethality. Mutations in the genes encoding the major fibrillar collagen types I and III have been demonstrated in EDS types VII and IV, respectively, while mutations in the lysyl hydroxylase and ATP7A genes, with roles in collagen cross-linking, are responsible for EDS types VI and IX. The biochemical and molecular bases for the most common forms of EDS (types I, II and III) are unknown. Here, we describe a balanced translocation between chromosome 9 and an X chromosome that disrupts the minor fibrillar collagen type V gene COL5A1 in a patient with both EDS type I and hypomelanosis of Ito. The breakpoint occurs at 9q34 within COL5A1 intron 24 and interestingly, within a LINE-1 (L1) element at Xp21.1. A fusion mRNA between COL5A1 and an Alu sequence is produced, but no aberrant protein is detectable. Rather, the amount of type V collagen is reduced in the patient's fibroblasts, suggesting haploinsufficiency as a cuase of the phenotype. This demonstrates that a mutation in a type V collagen gene, COL5A1, results in EDS type I, and shows the involvement of L1 sequences in a constitutional chromosomal translocation. Because collagen type V is a heteromorphic protein in which molecules may be composed of polypeptides encoded by three COL5A genes, this suggests all three genes as candidates for mutations in EDS.
Chondrodysplasia punctata, a skeletal dysplasia with craniofacial dysmorphism and joint contractures can occur with rhizomelia, mesomelia or both. The rhizomelic form is generally lethal, whereas one form of mesomelic chondrodysplasia punctata has been described that is associated with a presumably normal lifespan and intelligence. We describe a case of a fetus suspected prenatally of having rhizomelic chondrodysplasia punctata, who was subsequently diagnosed at 1.5 years of age to have the tibia-metacarpal form of chondrodysplasia punctata. The prenatal sonographic findings of second-trimester micromelic bone shortening and third-trimester proximal femoral stippling may be present in the rhizomelic form but are not specific to this condition.
We describe a boy with low birth weight, congenital microcephaly, multiple minor facial anomalies, cleft palate, soft tissue syndactyly of fingers and toes, and moderate to severe mental retardation. Literature review suggested 6 possible diagnoses, including Scott craniodigital syndrome, Chitayat syndrome, Filippi syndrome, Zerres syndrome, Kelly syndrome, and Woods syndrome. Each has as part of the phenotype craniofacial anomalies and soft tissue syndactyly of fingers and toes; and superficially, distinction among the 6 may be difficult. However, based on the phenotype analysis we performed, we conclude that our patient has Filippi syndrome, and thus is the first reported case from the United States.
We report a male with features of frontonasal dysplasia, but also with ocular and auricular defects. This child most likely has oculoauriculofrontonasal syndrome, an autosomal recessive syndrome first described in 1981. We also review the literature on this syndrome, and discuss differential diagnosis.
CHARGE association is a heterogeneous condition that affects several organ systems, including the eye, ear, nose, heart, and genitals. Hearing loss is a common finding in CHARGE association; therefore, audiologists and otolaryngologists need to be familiar with this relatively common entity.
Several patients with mandibulo-acral dysplasia have been described, although it is becoming clear that the phenotype is quite variable, both with regards to clinical findings and age of onset. This is a review of the literature on mandibulo-acral dysplasia, as well as a discussion on variability versus heterogeneity in this entity.
Explore the source record for details and available documents.
We report a mother and daughter who have hypertelorism, mild limb defects, umbilical hernia/omphalocele, natal teeth and minor craniofacial anomalies. These individuals represent the third family with Teebi hypertelorism syndrome, a rare autosomal dominant syndrome.
Stippled epiphyses occur in several monogenic, teratogenic, or aneuploidy syndromes. We describe two sibs with a provisionally unique chondrodysplasia punctata syndrome, who have, in addition to stippled epiphyses, minor facial anomalies, short stature, and ocular colobomata. Inheritance of this condition is likely autosomal recessive.