Atelencephalic microcephaly: a case report and review of the literature.

UNLABELLED: Atelencephalic microcephaly is a lethal form of abnormal cerebral development. In atelencephaly there is a rudimentary prosencephalon; in aprosencephaly, a more severe form of cerebral malformation, both prosencephalic and diencephalic derivatives fail to develop; both conditions form the aprosencephaly/atelencephaly spectrum (AAS). In the literature 20 cases with atelencephaly or aprosencephaly have been described. Except for the brain malformation other congenital abnormalities seem to be present more often in patients with aprosencephaly. In two patients (one with atelencephaly and one with aprosencephaly) an aberration of chromosome 13 was found. We report on a prematurely born microcephalic male infant with a severely malformed calvarium with overlying rugged skin, non-fused cranial sutures, absent fontanelles, and multiple contractures. CT scan of the brain revealed neither cerebral hemispheres, nor ventricles and a diagnosis of atelencephalic microcephaly was made. In the literature two sibs have been described, products of consanguineous parents, who were the only ones with cerebellar dysgenesis. Aprosencephaly/atelencephaly spectrum in combination with cerebellar dysgenesis seems to be an autosomal recessive syndrome. CONCLUSIONS: Atelencephalic microcephaly is a distinct entity and should be differentiated from anencephaly and the fetal brain disruption sequence. The aetiology of the disorder is unknown.

Restrictive dermopathy. Report of 12 cases. Dutch Task Force on Genodermatology.

BACKGROUND: This study describes 12 cases of restrictive dermopathy seen during a period of 8 years by the Dutch Task Force on Genodermatology. We present these unique consecutive cases to provide more insight into the clinical picture and pathogenesis of the disease. OBSERVATIONS: Clinical features in more than 85% of these children were prematurity, fixed facial expression, micrognathia, mouth in O position, rigid and tense skin with erosions and denudations, and multiple joint contractures. Ten patients underwent histopathologic skin biopsy. The biopsy results showed flattening of rete ridges in all 10 patients, a thin dermis with collagen aligned parallel to the epidermis in 9 patients, and poorly developed dermal appendages in 9 patients. Additional findings in individual patients included blepharophimosis, inguinal skin tear, skin tear in the frontal neck area that developed during delivery, absent eyelashes, a wide ascendent aorta, and dextrocardia. Fibroblast cultures taken from 5 patients did not show abnormal alpha 2 beta 1 and alpha 1 beta 1 integrin expressions. CONCLUSIONS: The alleged rarity of restrictive dermopathy may be partially caused by medical unfamiliarity with this entity, despite its characteristic clinical and histopathologic picture. The pathogenesis of the disease still needs to be elucidated.

Bruck syndrome: a rare combination of bone fragility and multiple congenital joint contractures.

Bruck syndrome manifests with combined features of arthrogryposis and osteogenesis imperfecta. It is a distinct autosomal recessive disorder with normal collagen I. The main features are osteoporosis, bowing of the long bones, scoliosis due to vertebral deformities, and congenital joint contractures. The presence of arthrogryposis differentiates this syndrome from "classical" osteogenesis imperfecta. A family with three affected children is presented with a review of the literature.

Prenatal and postnatal investigation of a case with Miller-Dieker syndrome due to a familial cryptic translocation t(17;20) (p13.3;q13.3) detected by fluorescence in situ hybridization.

We present here a case report of a fetus with a kidney anomaly and dilated occipital horns, detected initially by echoscopy at 29 weeks' amenorrhoea. After 31 weeks of gestation, the proband was born with clinical symptoms of Miller-Dieker syndrome. This was subsequently confirmed by fluorescence in situ hybridization (FISH), but not by conventional cytogenetic analysis. FISH using a cocktail of cosmids (c197-2, c197-4, c197-9) from the Miller-Dieker critical region showed a deletion of 17p13.3 in one homologue of chromosome 17. Additional FISH studies revealed a subtle 17p;20q translocation in the father, his sister, and the paternal grandmother. Hence, our patient is a carrier of an unbalanced 17;20 translocation resulting in a partial deletion of 17p and a partial trisomy 20q. Whenever kidney anomalies and dilated occipital horns are observed together with polyhydramnios during prenatal ultrasound examination, the possibility of Miller-Dieker syndrome should be suspected. In such cases, prenatal and/or postnatal chromosome studies should also include FISH analysis with the appropriate probes.

Deletions spanning the neurofibromatosis type 1 gene: implications for genotype-phenotype correlations in neurofibromatosis type 1?

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder characterized by abnormalities of tissues predominantly derived from the neural crest. Symptoms are highly variable and severity cannot be predicted, even within families. DNA of 84 unrelated patients with NF1, unselected for clinical features or severity, were screened with intragenic polymorphic repeat markers and by Southern analysis with cDNA probes. Deletions of the entire gene were detected in five patients from four unrelated families. Their phenotype resembled that of five previously reported patients with deletions, including intellectual impairment and dysmorphic features, but without an excessive number of dermal neurofibromas. This report supports the hypothesis that large deletions spanning the entire NF1 gene may lead to a specific phenotype.

Unbalanced karyotype, dup 14(q13-q22), in a mother and her two children.

A duplication of chromosome 14(q13-q22) caused mild mental retardation and some dysmorphic features in two children and their mother. The unbalanced karyotype did not affect the fertility of the mother. Fluorescent in situ hybridization, with a chromosome 14 specific paint, was used to confirm that the inserted material was from chromosome 14.

Paternal duplication of chromosome 5q11.2-5q14 in a male born with craniostenosis, ear tags, kidney dysplasia and several other anomalies.

A de novo duplication of the proximal part of the long arms of chromosome 5 was found in a male born with craniostenosis, ear tags and kidney dysplasia. The nature of the chromosomal aberration was defined by fluorescence in situ hybridization and the origin of the duplication was traced by polymorphic DNA markers. A comparison is made with the published cases showing similar duplications in the long arm of chromosome 5.

Ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia: a second case of the AREDYLD syndrome.

A 19-year-old female with ectodermal dysplasia, lipoatrophy, diabetes mellitus, and amastia is described. This complex of symptoms is very similar to that of a case published by Pinheiro et al [1983] under the acronym of AREDYLD syndrome.

A fetal cystic neck mass associated with maternal tuberous sclerosis. Case report and literature review.

Tuberous sclerosis is a single gene autosomal-dominant disorder, characterized by multiple hamartoma formation. It shows a wide variability of expression. Prenatal diagnosis by means of a DNA or biochemical marker is not yet possible. Ultrasound offers the only way to detect possible antenatal hamartoma formation, which is most commonly found in the central nervous system, the renal system, and the heart. We report a case of fetal involvement that appears unique because of the unusual location of a tumour in the neck of the fetus.

The Rapp-Hodgkin syndrome.

We report on a family with the Rapp-Hodgkin ectodermal dysplasia syndrome. Four affected family members are described and a review of the literature is given.