Orofaciodigital syndrome type IV: report of a patient

We describe a further patient with the orofaciodigital syndrome type IV. The clinical characteristics include lobulated tongue, pseudo-cleft of lip, pre- and postaxial polydactyly of hands and feet, severe talipes equinovarus, mesomelic limb shortness associated with tibial hypoplasia, and severe bilateral deafness. Five similar cases including the present patient are now on record. Autosomal recessive inheritance is likely.     

Orofaciodigital syndrome with mesomelic limb shortening.

Two sisters, the children of first cousin Pakistani Moslem parents, have unusual facies, tongue hamartomata, pre- and postaxial polydactyly, severe talipes, and mesomelic limb shortening associated with tibial dysplasia. Homozygosity for a recessive gene defect is probable. The phenotype resembles, but is distinct from, the orofaciodigital syndromes delineated to date. We suggest that this condition be labelled OFD IV.     

Orofaciodigital syndrome type I in a girl with unilateral tibial pseudarthrosis.

The orofaciodigital syndromes are a group of possibly seven different malformation syndromes including oral, facial, and digital malformations. Type I has X linked dominant inheritance whereas the other types show autosomal recessive inheritance. An exact diagnosis is therefore important for genetic counselling. We here report a girl with orofaciodigital syndrome type I. She had cystic kidney disease at the age of 8 months which has not previously been reported in an infant with orofaciodigital syndrome. In addition she had unilateral tibial pseudarthrosis which has only rarely been reported in the orofaciodigital syndromes and in type II only.     

Short rib-polydactyly syndrome (SRPS) with anencephaly and other central nervous system anomalies: A new type of SRPS or a more severe expression of a known SRPS entity?

We describe two patients with short rib-poly-dactyly syndrome (SRPS) from two unrelated Spanish families. These patients present clinical and radiological characteristics that overlap those of the different established types of SRPS. In addition, one patient had anencephaly and the other patient had severe brain abnormalities with a family history of an older sister with anencephaly, and a brother diagnosed with SRPS. This second family is interesting in that the two affected brothers present with different clinical and radiological findings; for example, one had ovoid tibiae and the other did not. This particular family shows that intrafamiliar variation is also observed within SRPS. It remains unsettled whether these cases might be considered a new type of SRPS or a variant of an established entity or whether the differences between the SRPS represent variability or heterogeneity. Molecular studies may answer this question in the near future. © 1993 Wiley-Liss, Inc.     

Orofaciodigital syndrome type I associated with polycystic kidneys and agenesis of the corpus callosum.

We report a female case of orofaciodigital syndrome type I (OFD I) associated with polycystic kidneys and agenesis of the corpus callosum. She had chronic renal failure requiring maintenance dialysis and significant neurological deficits. Her mother had less severe OFD I associated with polycystic kidneys but her renal function was normal and there was no clinical or radiological evidence of a structural abnormality of the brain.     

Joint dislocation and cerebral anomalies are consistently associated with oral-facial-digital syndrome type IV

We present a female patient with the oral-facial-digital syndrome type IV. Our report, the tenth in the literature, describes the typical manifestations of the syndrome, combined with malformations and deformations which have not always been described in the previously reported cases. They include cerebral and renal anomalies, anal atresia and dislocation of elbows and knees.     

Natural history of the oldest known females with mucopolysaccharidosis type IVA (Morquio A syndrome)

Mucopolysaccharidosis Type IVA (MPS IVA), also known as Morquio A syndrome, is an autosomal recessive lysosomal storage disorder that results from variants in the GALNS gene that encodes the enzyme galactosamine‐6‐sulfate sulfatase. This syndrome has systemic manifestations including, but not limited to, musculoskeletal, respiratory, cardiovascular, rheumatologic, neurologic, dental, ophthalmologic, and otologic. This condition is usually detected within the first few years of life with an average life expectancy of 25.3 ± 17.43 years. We report the natural history of two of the oldest known females with MPS IVA, who were each clinically diagnosed at 4 years of age and who are now 74 and 70 years of age, respectively. They are both affected by pathogenic variants c.319G>A (p.Ala107Thr) and c.824 T>C (p.Leu275Pro) in the GALNS gene.     

Inheritance of Ehlers-Danlos type IV syndrome.

The Ehlers-Danlos type IV syndrome is a severe disease with premature death from catastrophic tearing of large arteries and a tendency to intestinal rupture. These patients lack the genetically distinct type III collagen. Here evidence is presented that obligate heterozygotes have lowered levels of type III collagen in their skin and that their cultured fibroblasts produce less than normal amounts of this protein. The inheritance is autosomal recessive.     

Survival and spectrum of anomalies in the Meckel syndrome

We present two sisters whose malformations (hydrocephalus, cystic dysplasia of the kidneys, polydactyly, and cleft palate) are consistent with a diagnosis of the Meckel syndrome. Diagnosis in case 1 was delayed because of two factors: 1) prolonged survival (28 mo), and 2) the absence of severe craniofacial malformations. These two factors may create difficulties in making this diagnosis and result in uncertainty regarding the medical prognosis of the infant and the genetic prognosis for the parents.     

The spectrum of pathological changes in severe acute respiratory syndrome (SARS)

AIMS: To analyse the lung pathology of severe acute respiratory syndrome (SARS) and correlate the findings with the time sequence of the disease. METHODS AND RESULTS: Ten patients with a clinical diagnosis of SARS, and virological confirmation of SARS coronavirus infection were identified. Histology in most cases showed diffuse alveolar damage, from early to late phases, and the changes corresponded to the time sequence. Other variable features include multinucleated giant cells, pneumocytes with cytomegaly and variable amounts of inflammatory cells and foamy macrophages. One case showed superimposed bronchopneumonia. No viral inclusions were found. Coronavirus particles were identified in pneumocytes by electron microscopy. CONCLUSIONS: The predominant pathological process of SARS is diffuse alveolar damage and, in patients who die from the disease, there is evidence of organization and fibrosis. There are apparently no histological features specific for this disease, and the aetiological diagnosis depends on virological and ultrastructural studies.     

Ehlers-Danlos syndrome type IV (EDS IV) as model of a defective biopolymer composite material

The connective tissue of a lethal EDS IV case was investigated for the reasons of the manifested disturbances of the arterial wall. This functional disorder was attributed to the mechanical decoupling of elastin and collagen, with the premise of a composite material consisting of cellular, fibrillar, lamellar and other matrix components. A conceivable relation between the manifested deficiency of type III collagen and a disturbed anchoring of elastin is shown. These findings are supported by biochemical, morphological, x-ray and mechanical data.     

Lacrimo-auriculo-dento-digital (LADD) syndrome with renal and foot anomalies

A patient who presented with most features of lacrimo-auriculo-dento-digital (LADD) syndrome, an autosomal dominant trait, is described. There was no deafness, and anomalies of the external ear and the upper limbs were discrete. Renal anomalies, consisting of progressive caliectasis with stone formation, were revealed by macroscopic hematuria. There were also skeletal anomalies of both feet, a feature not previously described. Renal and distal limb anomalies are probably features of LADD syndrome.     

Vohwinkel syndrome (mutilating keratoderma) associated with craniofacial anomalies

We describe a female patient with Vohwinkel syndrome (mutilating palmoplantar keratoderma), who in addition showed cleft lip and palate, microcephaly, facial asymmetry, and other anomalies. © 1994 Wiley-Liss, Inc.     

Craniofacial,limb, and abdominal anomalies in a distinct syndrome: Relation to the spectrum of Pfeiffer syndrome type 3

Presented are 2 patients with abnormal craniofacial region, limbs, and abdomen, features that may be consistent with Pfeiffer syndrome, type 3. Both patients had bicoronal and bisphenoidal synostosis, extreme exophthalmic midface hypoplasia, and hydrocephalus. The limbs had a fixed flexion deformity of the elbows with broad thumbs which were radiopalmarly deviated; the toes were broad with a varus deformity and syndactyly of toes 2–5. Both patients developed bowel obstruction secondary to midgut malrotation, and one of the patients had prune belly syndrome. Review of the literature disclosed an additional patient who, in retrospect, had Pfeiffer syndrome type 3 and midgut malrotation. These patients suggest that intestinal malrotation with or without prune belly syndrome may be a common component of this entity. © 1993 Wiley-Liss, Inc.     

Simultaneous expression of 70 kilodalton type IV collagenase and type IV collagen alpha 1 (IV) chain genes by cells of early human placenta and gestational endometrium.

BACKGROUND: In this study we used in situ hybridization to investigate the expression of the genes 70 kilodalton (kd) collagenase and the alpha 1(IV) collagen chain of type IV collagen in cells of early human placenta and gestational endometrium. EXPERIMENTAL DESIGN: The aim was to study the spatial distribution of these gene expressions within a developing tissue which possesses physiologic invasive potential. The results obtained for the 70 kd type IV collagenase mRNA expression were also compared with the immunohistochemical distribution of the corresponding antigen. RESULTS: Expression of mRNAs for these proteins was found in cells of trophoblastic columns, stromal cells of villi and in cells of decidua and endometrial stroma. The only differences between the expressions was the lower level of signals for 70 kd type IV collagenase in fibroblastic stromal cells and endothelial cells of villi and in the pericytic cells of spiral arteries. Otherwise the results for both types of mRNA were comparable. We also studied the immunohistochemical distribution of the 70 kd type IV collagenase using specific monoclonal antibodies against the enzyme. Immunohistochemistry supported well the findings obtained by in situ hybridization. CONCLUSIONS: The results indicate that the genes for the 70 kd type IV collagenase and for the alpha 1(IV) collagen chain are simultaneously active in cells of placenta and gestational endometrium and the same cells which produce type IV collagen also can produce the cleaving enzyme, the 70 kd type IV collagenase. The results also show that the cytotrophoblastic cells, which during early pregnancy invade the extracellular matrix and spiral arteries of uterine wall contain significant amount of mRNA for the 70 kd type IV collagenase. This finding supports the concept that the 70 kd type IV collagenase would be important for invasion, and in the case of this study, also for the physiologic invasion of placental cytotrophoblasts.     

Oculoectodermal syndrome with coarctation of the aorta and moyamoya disease: expanding the phenotype to include vascular anomalies

Oculoectodermal syndrome (OES, OMIM 600268) is characterized by discrete areas of alopecia of the scalp and epibulbar dermoids which are present from birth, with additional variable anomalies. We describe two patients, one of whom has been reported [Lees et al. (2000); Am J Med Genet 91:391–395], who both had coarctation of the descending aorta and moyamoya disease, and developed epilepsy, recurrent transient ischemic attacks, and cerebrovascular accidents during early childhood. We suspect that the vascular findings are an integral part of the syndrome. © 2011 Wiley‐Liss, Inc.