Heterozygous manifestations of Langer mesomelic dysplasia

The mesomelic dysplasias are a heterogeneous group of genetic disorders with predominant skeletal manifestations in the forearms and shanks. We have documented, over a thirteen-year period, the clinical and radiographic course of the condition in a boy with the Langer type of mesomelic dysplasia. It has been suggested that dyschondrosteosis or the Madelung deformity are the phenotypic manifestations of the gene which causes Langer mesomelic dysplasia in the homozygote. Several relatives on both sides of the family which we studied had malformations of their forearms, in keeping with this concept. However, these anomalies differed from those of dyschondrosteosis and the classical Madelung deformity; the exact syndromic status of the heterozygous phenotype remains unsettled.     

Dominant ano-rectal malfromatin,nephritis and nerve-deafness: a possible new entity?

A family is presented in which ano-rectal malformation and features common to Alport Syndrome appear to be present in three generations. The possibility of a new syndrome based on a single gene defect is discussed.     

Generalized enchondromatosis in a boy with only platyspondyly in the father

We report on a boy with platyspondyly and metaphyseal manifestations of enchondromatosis with severe involvement of hands and feet, compatible with generalized enchondromatosis (enchondromatosis Spranger type VI). His father has only moderate platyspondyly. The latter is either coincidental or a milder, more localized expression of the disease. Father and son have consanguineous parents suggesting autosomal recessive inheritance of the trait. However, autosomal dominant inheritance with variable expressivity is also possible.     

Ectrodactyly (split-hand/split-foot) and ectodermal dysplasia with normal lip and palate in a four-generation kindred

Five members of a four-generation Mauritian family with ectrodactyly (split-hand/split-foot deformity) and ectodermal dysplasia but without clefting of the lip or palate have been investigated. The ectrodactyly ranged from virtual normality to severe tetramelic deficiencies. The ectodermal dysplasia manifested as hypotrichosis and abnormal dentition. Distinction is drawn between this autosomal dominant condition and the classical EEC syndrome; independent syndromic status is proposed.     

Radiographic and morphologic findings in a previously undescribed type of mesomelic dysplasia resembling atelosteogenesis type II

The mesomelic chondrodysplasias are a heterogeneous group of dwarfing disorders characterized by shortness of the middle segments of limbs. We report on a 25-week fetus with disproportionate shortness of limbs with an apparently distinct form of mesomelic dysplasia. Radiographic findings at necropsy included ulnar deviation of hands, talipes equinovarus, distal tapering of the humeri, and hypoplastic fibulae, radii, and ulnae. Chondro-osseous morphology showed mild shortness of the physeal columns, overgrowth of perichondral bone, peripheral ingrowth of mesenchymal cells into the physis, and numerous areas of fibrillar degeneration with rings of collagen surrounding the chondrocytes. Ultrastructural findings included a degenerated territorial matrix, pericellular halos of collagen, and dilated loops of rough endoplasmic reticulum in chondrocytes. The radiographic appearance of the long bones is distinct from that of previously described mesomelic dysplasias. The chondro-osseous morphologic findings and the distal tapering of the humerus are somewhat reminiscent of atelosteogenesis type II, but the pattern of matrix degeneration and the presence of inclusion bodies in the chondrocytes distinguish it from disorders of sulfate transport. Am. J. Med. Genet. 80:247–251, 1998. © 1998 Wiley-Liss, Inc.     

Hair-nail dysplasia - a new pure autosomal dominant ectodermal dysplasia

An apparently hitherto undescribed pure ectodermal dysplasia of the tricho-onychic subgroup is described. Its cause is an autosomal dominant gene with complete penetrance and variable expressivity. Differential diagnosis considered 18 conditions belonging to the same subgroup, as well as Clouston syndrome. This report increases the number of conditions of the tricho-onychic subgroup to 19, and the total number of ectodermal dysplasias to 155.     

Acromicric dysplasia: long term outcome and evidence of autosomal dominant inheritance

Acromicric dysplasia is a rare bone dysplasia characterised by short stature, short hands and feet, normal intelligence, mild facial dysmorphism, and characteristic x ray abnormalities of the hands. Only a very small number of children with this condition have been reported so far. Here we report on a series of 22 patients including 10 boys and 12 girls with acromicric dysplasia. Length was normal at birth and height fell progressively off the centiles postnatally. The mean adult height was 130 cm (133 cm in males, 129 cm in females). The hands, feet, and limbs were short and OFC was normal. Intelligence was normal and mild dysmorphic features were noted. Other occasional features included well developed muscles, a hoarse voice, generalised joint limitation in some patients, frequent ear, tracheal, and respiratory complication, and spine abnormalities. Long term follow up showed that facial dysmorphism was less obvious in adults and that carpal tunnel syndrome was frequent in older patients. Apart from short metacarpals and phalanges, internal notch of the second metacarpal, external notch of the fifth metacarpal, and internal notch of the femoral heads, there were no major x ray abnormalities. No major complications, such as cardiac disease or major orthopaedic problems, occurred in the course of the disease. The condition appeared to be sporadic in 16 cases but the observation of vertical transmission in three families was consistent with an autosomal dominant mode of inheritance.


Keywords: acromicric dysplasia; geleophysic dysplasia; long term outcome; autosomal dominant inheritance     

Progeroid syndrome with characteristic facial appearance and hand anomalies in father and son

We report on the father-to-son transmission of a progeroid syndrome characterized by facial anomalies, sparse subcutaneous fat, and hand anomalies including syndactyly, camptodactyly, and finger deviation. Mild mental retardation, microcephaly, and congenital heart defect were found only in the son. To our knowledge, this syndrome has not been described previously. Am. J. Med. Genet. 73:227–229, 1997. © 1997 Wiley-Liss, Inc.     

Spondyloepiphyseal dysplasia in a cape town family: Linkage with the gene for type II collagen (COL2A1)

A moderately severe form of autosomal dominant (AD) spondyloepiphyseal dysplasia (SED) has been documented in 14 individuals in 3 generations of a family in Cape Town, South Africa. Affected persons had a short trunk; radiographic investigations indicated that skeletal involvement was worst in the hips and spine. Linkage studies with restriction fragment length polymorphisms (RFLPs) associated with the COL2A1 gene and the phenotype yielded a maximal LOD score of 4.51 at theta = 0.00. This result suggests that the structural locus for type II collagen is primarily involved in the pathogenesis of this form of SED. © 1992 Wiley-Liss, Inc.     

A new syndrome with cardiac malformation,cleft lip-palate,microcephaly and digital anomalies?

A family with cardiac malformation, cleft lip-palate, short stature, microcephaly, distally placed thumbs, short 2nd and 5th fingers, long and broad 1st toes, broad distance between 1st and 2nd toes and mediodorsal curvature of the 4th toes with syndactyly of the 2nd and 3rd toes has been described as having a new syndrome. While some members of the family had full signs of the syndrome, others had similar but fewer and less severe anomalies of the same structures. The presence of common findings in three generations, its variable expressivity and pleiotropism, and the non-consanguineous history in the parents suggest that the inheritance is autosomal dominant.     

Apparent dominant transmission of the Rubinstein-Taybi syndrome

The cause of the Ruinstein-Taybi syndrome (RTS), a multiple congenital anomalies/mental retardation (MCA/MR) syndrome first described in 1963, remains obscure. Recently, a deletion of chromosomal material at 16p13.3 has been found in some patients with the disorder, but no such deletion can be identified in the majortity of affected individuals. Although the disorder has been well documented to be concordant in at least 7 monozygotic twin pairs and in one non-twin sib pair, only one clear-cut case of parent-to-child transmission has been reported previously. We present here a mother and daughter, both of whom appear to be affected with RTS, strongly suggesting either autosomal or X-linked dominant transmission. The paucity of previous cases of parent-to-child transmission may be related to either decreased fertility or decreased fitness in affected individuals. © 1993 Wiley-Liss, Inc.     

A new short rib syndrome: Report of two cases

We describe two unrelated malformed infants who died shortly after birth and who had multiple congenital anomalies including hydrops and ascites, facial abnormalities (with median cleft of the upper lip), narrow thorax, protuberant abdomen, and short, bowed limbs. Postmortem radiographs showed very short ribs and disproportionately short long tubular bones; no metaphyseal abnormalities were present. Comparison with earlier described short-rib/short-rib-polydactyly syndromes suggest that the disorder present in our two cases is a new type of short-rib syndrome. One of our patients was born to a consanguineous couple; in a subsequent pregnancy, real-time ultrasonography in the second trimester showed that the female fetus had the same abnormalities as its sib. Diagnosis was confirmed after elective abortion. This suggests that this short-rib syndrome may be an autosomal recessive disorder.     

A new nail dysplasia syndrome with onychonychia and absence and/or hypoplasia of distal phalanges

A family in which two generations have a rare and previously undescribed form of nail dysplasia with bone abnormalities is reported. This disorder is characterized by onychodystrophy, anonychia, brachydactyly of the fifth digit of the hands, and digitalization of the thumbs, with absence and/or hypoplasia of the distal phalanges of the hands and feet. The probable mode of transmission is autosomal dominant.     

Dominant mesomelic dysplasia,ankle, carpal,and tarsal synostosis type: A new autosomal dominant bone disorder

A new type of mesomelic dysplasia was in 3 generations of a large Thai family. It is characterized by bilateral symmetrical marked shortening of the ulnae and shortening and bowing of the radii. The proximal fibula is usually short and synostoses are present between the tibia and fibula and the small malformed calcaneus and talus. The prominent calcanei on the ventral surfaces of the distal fibulae are a characteristic feature of the new type. Carpal and tarsal synostoses are present in some affected people. All affected individuals walk on the tips of their toes with the dorsal foot deviated laterally. The deformities of the radius and ulna somewhat resemble those of mesomelic dysplasia, Langer type, but otherwise the condition is distinctly different. This new mesomelic dysplasia is an autosomal dominant trait with complete penetrance and variable expressivity over 3 generations. © 1992 Wiley-Liss, Inc.     

Ectodermal dysplasia,Rapp-Hodgkin type in a mother and severe ectrodactyly-ectodermal dysplasia-clefting syndrome (EEC) in her child

We describe a mother with manifestations most consistent with the Rapp-Hodgkin type of ectodermal dysplasia and her malformed newborn son with ectrodactyly, ectodermal dysplasia, cleft palate, and bilateral cystic and obstructive ureteroceles with hydroureters and cystic renal dysplasia as described in the EEC syndrome. This observation suggests that the Rapp-Hodgkin type of ectodermal dysplasia and EEC syndrome, both defined as autosomal dominant conditions with variable expression, may be manifestations of the same mutated gene. We also want to emphasize that urogenital anomaly is another hallmark of the EEC syndrome. © 1996 Wiley-Liss, Inc.     

Autosomal dominant (Beukes) premature degenerative osteoarthropathy of the hip joint unlinked to COL2A1

Molecular investigations have been undertaken in several separate large South African families with autosomal dominant skeletal dysplasias in which premature degenerative osteoarthropathy of the hip joint was the major manifestation. There are sometimes additional minor changes in the spine and these conditions fall into the general spondyloepiphyseal dysplasia (SED) nosological category. In some kindreds, linkage between phenotype and the type II collagen gene (COL2A1) has been established, while in others there is no linkage. We have now completed molecular linkage investigations in an Afrikaner family named Beukes, in which 47 members in 6 generations have premature osteoarthropathy of the hip joint. A LOD score of minus infinity indicates that this condition is not the result of a defect of the COL2A1 gene. © 1994 Wiley-Liss, Inc.     

The cerebro-reno-digital syndromes: a new community

Two "new" syndromes of multiple congenital malformations with autosomal-recessive inheritance are presented. One syndrome, found in 2 sibs of nonconsanguineous parents, included microcephaly, agencies of the corpus callosum, pterygium colli, cystic renal dysplasia (CRD) and postaxial polydactyly (PP). The other, found in 2 female sibs of consanguineous parents, included micropolygyria, CRD, PP, and polysplenia. The literature review allows the delineation of a community of 19 "cerebro-reno-digital" syndromes with autosomal recessive inheritance, 14 of which include cerebral anomalies, CRD and PP. Three more autosomal recessively inherited syndromes had CRD (or renal fibrosis) and cerebral anomalies (without digital anomalies), three others involved cerebral and digital anomalies (without renal anomalies), and one further syndrome showed CRD and ectrodactyly (without cerebral defects). Such phenotypical similarity may be attributed to the fact that there are common links in the pathogenesis of the syndromes under study.     

Congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media: Further evidence that interruption of early embryonic blood supply may result in Adams-Oliver (plus) syndrome

In this report we describe a male patient with the interesting combination of a large congenital scalp defect, distal limb reduction anomalies, right spastic hemiplegia and hypoplasia of the left arteria cerebri media. Follow-up data from birth up to the age of 18 years revealed positive evolution with low to normal intelligence. The findings in the present patient, i.e. an Adams-Oliver syndrome associated with a severe neurological deficit, are best explained as resulting from interruption of the early embryonic blood supply.