Acromicric dysplasia and geleophysic dysplasia: similarities and differences.

UNLABELLED: We report on a girl with severe growth retardation, characteristic facies, short stubby hands and feet, progressive joint stiffness, mild aortic and mitral valve insufficiency, and normal intelligence. These features are compatible with the diagnosis acromicric dysplasia. The differential diagnosis with Moore-Federman syndrome and geleophysic dysplasia is discussed; major points to consider in differentiating these entities are the facial appearance, the aspect of the proximal femora, and the presence or absence of storage phenomena. The differences in pattern of inheritance are important in adequate patient care, especially in genetic counselling. CONCLUSION: Acromicric dysplasia, geleophysic dysplasia, and Moore-Federman syndrome may be allelic forms of the same disorder or different disturbances of the same metabolic pathway.

A Croatian case of the Schinzel-Giedion syndrome.

The Schinzel-Giedion syndrome is an infrequently described malformation syndrome, mainly characterized by a profound mental deficiency, a typical face including a midface hypoplasia, urogenital abnormalities, and minor radiographic features. Death prior to two year of age is the rule. A boy with typical features of the syndrome is described. He died at the age of 21 months. This is the first case of this syndrome reported from Croatia. The recurrence in only one of the 20 families, does not firmly sustain an autosomal recessive pattern of inheritance, although this still remains possible.

Metacarpophalangeal pattern profile analysis in Sotos and Marfan syndrome.

Patients with Sotos and Marfan syndrome have unusually long metacarpals and phalanges which may make the differential diagnosis difficult in younger children. Using Q-scores, we compared metacarpophalangeal pattern profile (MCPP) analysis in these two syndromes and identified distinct and different pattern profiles. This illustrates that the MCPPs are specific in these syndromes, even at an early age, and not related solely to the unusually long metacarpals and phalanges. For this study we used data from 50 Sotos patients (34 from the United Kingdom and 16 from the Netherlands, with a total of 95 hand films) and 36 Marfan patients (from the Netherlands, with 98 hand films). Of all patients over age 3 years the bone length (including the epiphysis) was determined. The patients under 7 1/2 years (29 Sotos and 12 Marfan) were also measured without inclusion of the epiphysis. The patients measured without epiphysis had a relative short metacarpal 1 (MC1) and long distal phalanx 1 (DPh1) in Sotos syndrome, and a relative long MC1 and short DPh1 in Marfan syndrome. Between age 3 and 7 1/2 years more than 90% of the films could be classified correctly using these two variables. Of the roentgenograms measured with epiphyses, about 80% were classified correctly.

Clinical and biochemical observations in a patient with combined Pompe disease and cblC mutation.

Metabolic studies are described in a patient who presented at 3 weeks of age with severe anaemia, hyperbilirubinaemia and hypotonicity. Clinically, glycogen storage disease type II (Pompe disease) was suspected because of a massively enlarged heart and hepatosplenomegaly. This was confirmed biochemically by the demonstration of glycogen accumulation in skeletal muscle and undetectable acid alpha-1,4-glucosidase activity in fibroblasts. Further biochemical studies in this patient surprisingly revealed homocystinuria and methylmalonic aciduria, suggesting a defect in the uptake, transport or intracellular metabolism of vitamin B12. Studies in cultured fibroblasts from the patient revealed a low uptake of [57Co]cyanocobalamin and an impaired intracellular conversion to both 5'-deoxyadenosylcobalamin and methylcobalamin. Moreover, the incorporation of labelled propionate into proteins as well as the formation of labelled methionine from labelled 5-methyltetrahydrofolate was deficient in fibroblasts from the patient. Complementation studies revealed the presence of the cblC mutation in this patient. No treatment was initiated and the patient died at the age of 31 days. We conclude that the patient was affected by both glycogen storage disease type II and cblC disease. The remarkable combination of these two rare inborn errors can be the result of the consanguinity of the parents.

Piezogenic papules of the feet in healthy children and their possible relation with connective tissue disorders.

Piezogenic papules (PP) are pressure-induced lesions that appear on the heels while bearing weight, due to herniation of fat tissue into the dermis. They are present in the majority of adults. Because of the poor quality of connective tissue in hereditary disorders of connective tissue, such as the Ehlers-Danlos syndrome, it has been suggested that PP would be larger in number and diameter in this group of disorders. If papules are present, they might be painful as well. In view of this hypothesis 322 healthy pupils aged 4 to 13 years from a Dutch primary school were examined in order to study the prevalence and characteristics of piezogenic papules and signs of connective tissue disorders (Ehlers-Danlos) such as hypermobility and skin fragility. Of the 322 children investigated, 72% had one or more PP, the average number being five, with a mean diameter of 3.3 mm. The mean papule diameter increased with age and body weight. None of the papules were painful. Hypermobile joints occurred in 4.3% of the children. Mean body weight was the same in hypermobile and nonhypermobile children of the same age. The numbers of PP were equal in both groups, as was the number of children with and without PP. None of the children showed skin fragility. Our conclusion is that PP are present in the majority of healthy children, and are never painful.

[Attacks of apnea in an infant with achondroplasia]. / Apnoe-aanvallen bij een zuigeling met achondroplasie.

Infants and children with achondroplasia are at increased risk of sudden death because of apneic attacks caused by compression of the medulla oblongata or spinal cord by a constricted foramen magnum or narrow upper cervical spinal canal. This history of an infant with achondroplasia is discussed. As a result of apneic attacks she developed severe brain damage. Cervicomedullary compression was revealed at CT-scan and NMRI of the basicranium and upper cervical canal, and confirmed at decompressive surgery. Early symptoms can be clues to the existence of cervicomedullary compression. These clues are indication for further investigations. Decompressive surgery has good results when performed at an early stage. Knowledge of the signs and symptoms of cervicomedullary compression and of factors which increase the risk of complications are important in the management of achondroplastic patients.

Inherited syndrome of microcephaly, dyskinesia and pontocerebellar hypoplasia: a systemic atrophy with early onset.

A neurodegenerative disease is reported in 5 related families, belonging to a Dutch genetic isolate. Seven children (5 females, 2 males) had microcephaly, spastic pareses, severe extrapyramidal dyskinesia and failure to acquire any voluntary skills. Four died during childhood. Marked pontocerebellar hypoplasia and progressive cerebral atrophy were found by computed tomography of the brain. Autopsy in one case revealed widespread, progressive loss of neurons affecting the olivopontoneocerebellar system more severely than any other part of the brain, accounting for the macroscopic pontocerebellar hypoplasia. A neocortical biopsy from another patient indicated that rough endoplasmic reticulum in neurons as the earliest ultrastructural target of the pathological process. This study confirms the disease as an inherited neuronal degeneration with very early, probably prenatal onset.

Cerebrovascular disease in Ehlers-Danlos syndrome type IV.

We describe two patients with cerebrovascular complications of Ehlers-Danlos syndrome type IV. A 16-year-old girl with spontaneous internal carotid artery dissection and a 46-year-old woman with aneurysmal subarachnoid hemorrhage and multiple aortic dissections were both deficient in collagen type III, analyzed in cultured skin fibroblasts. To our knowledge, spontaneous carotid artery dissection associated with collagen type III deficiency has not been reported previously. Early clinical recognition of this syndrome is of great importance in view of the hazards of angiography and surgery. Collagen type III deficiency plays a role in the pathogenesis of intracranial saccular aneurysms and may also be involved in the pathogenesis of carotid cavernous fistulas and dissections of the cervical arteries.

Linkage data for Marfan syndrome and markers on chromosomes 1 and 11.

Six large families with classical Marfan syndrome were studied using markers on chromosomes 1 and 11. Two of three families tested showed negative scores using D1S7 but a third family gave a positive score (0.92) at theta = 0.1. The other chromosome 1 markers typed (MUCI, NGFB, D1S8) excluded close linkage. Negative lod scores with two chromosome 11q22 markers (D11S84, D11S148) excluded at least 20 cM in this area (Z = less than -2), which was chosen for study as two enzymes responsible for collagen degradation (collagenase and stromelysin) are localised to this region.

Mosaic 47,XY,+8/48,XXYY in a mentally non-retarded man with phenotypical and neurological abnormalities.

This report describes a non-retarded human male, mosaic for a 47,XY,+8 and a 48,XXYY cell line. The 47,XY,+8 cell line is present in approximately 70% of both lymphocytes and skin fibroblasts; 30% of the cells in both tissues have a 48,XXYY karyotype. Clinical abnormalities correspond mostly with the mosaic trisomy 8 syndrome.

A girl with the Pitt-Rogers-Danks syndrome.

A severely mentally retarded girl is presented, with symptoms as described by Pitt, Rogers, and Danks (pre- and postnatal growth retardation, and unusual facies). Additional manifestations are glaucoma, pre-auricular pits, and an atrial septal defect.

The poikiloderma of Rothmund-Thomson syndrome: changes in Langerhans cell morphology and distribution.

A black girl with the Rothmund-Thomson syndrome is presented. Immunophenotyping of subpopulations of immunocompetent cells in a biopsy of an atrophic hyperpigmented skin lesion revealed sparsity and unusual distribution of epidermal Langerhans cells. These cells were mainly located in the basal layer of the epidermis and did not show the usual dendritic pattern. Impressive immunoreactivity of the dermal infiltrate was observed by anti-HLA-DR staining. The changes in Langerhans cell morphology and distribution may indicate functional impairment of the up-regulating arm of skin immunity.

Clinical presentations of Ehlers Danlos syndrome type IV.

Ehlers Danlos syndrome type IV is an often lethal disease caused by various mutations of type III collagen genes. It presents in infancy and childhood in several ways, and the symptoms and signs include low birth weight, prematurity, congenital dislocation of the hips, easy inappropriate bruising (sometimes suspected as child battering), and a diagnostic facial phenotype. These features predict a lethal adult disease often complicated by fatal arterial rupture in early or middle adult life. Most affected patients can be diagnosed from radiolabelled collagen protein profiles by polyacrylamide gel electrophoresis. Prenatal diagnosis by specific type III collagen restriction fragment length polymorphisms is possible in some families, and will become increasingly important. Prenatal diagnosis and prevention of the disease in selected families is already possible and will be widely available in the future.

De novo partial trisomy 15q (proximal type).

This report describes a retarded girl with strabismus, high arched palate, antimongoloid slant, low set ears, hearing loss, micrognathia, short neck, and an anteriorly displaced anus. She was found to have a de novo partial trisomy of the proximal part of the long arm of chromosome 15.

Peroxisomal dysfunction in chondrodysplasia punctata, rhizomelic type.

The rhizomelic type of chondrodysplasia punctata (RCDP) is recognizable at birth because of the typical phenotype and radiological features. Most patients die young, some survive until their teens but all are severely retarded. Recent studies showed RCDP to be a peroxisomal disorder. Peroxisomal investigations may be important in defining the prognosis for an individual patient, and are definitely of use in antenatal diagnosis.

Long term survival of a patient with the cerebro-hepato-renal (Zellweger) syndrome.

A 13-year-old girl with severe mental retardation, tapetoretinal degeneration, an extinguished electroretinogram and sensoneurinal hearing loss is described. In early life the diagnosis of Zellweger (cerebro-hepato-renal) syndrome was considered because of hypotonia, craniofacial dysmorphia, abnormal liver functions and pipecolic aciduria. Biochemical studies in fibroblasts from the patient revealed a general peroxisomal dysfunction comparable to the findings in Zellweger Syndrome. As the clinical presentation of this patient is essentially different from that in classical Zellweger patients, who usually die early in life, we recommend the study of peroxisomal functions in all patients with severe mental retardation, tapetoretinal degeneration and sensoneurinal hearing loss.

Ito's hypomelanosis (incontinentia pigmenti achromians). A review of four cases.

In 1952 Ito described the occurrence of a bilateral systematized depigmented nevus in a 22-year-old Japanese woman. He used the term incontinentia pigmenti achromians. The condition has been described under various designations, such as for instance Ito's hypomelanosis. Till now 71 patients with this syndrome are described. We will report 4 cases, 2 boys and 2 girls, 2 Caucasian, 1 Indonesian and 1 Caribean child. The cutaneous signs in these 4 patients fit in with the syndrome of Ito's hypomelanosis. Of these 4 children 3 are mentally retarded, 2 have epilepsy. Congenital malformations are seen in 3 children. Electronmicroscopy of skin biopsies of the hypomelanotic nevus and of the normal skin were performed. In the biopsy of the normal skin of one patient interruption of the basement membrane is seen. Anomalies of the central nervous system as seen in our patients occur in about 40% of the cases. Abnormalities of skin derivatives next to other ectodermal anomalies are described. Affection of other germ layers also occur to a varying degree. In our 4 patients some of these abnormalities exist also. These 4 cases are presented to underline the fact that this syndrome seems not to be as extremely rare as is proposed.