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1.
Genet Couns ; 25(3): 315-20, 2014.
Article in English | MEDLINE | ID: mdl-25365854

ABSTRACT

Disruption in early pregnancy can cause severe and multiple congenital anomalies in a foetus. Three sequences, Limb-body wall complex (LBWC), amniotic band sequence (ABS) and body-stalk anomaly (BSA) are thought to be caused by disruption. This case report describes a foetus with severe multiple congenital anomalies, that fit the diagnoses of all three sequences, which might advocate these syndromes are a spectrum of one sequence.


Subject(s)
Abnormalities, Multiple/diagnostic imaging , Amniotic Band Syndrome/diagnostic imaging , Craniofacial Abnormalities/diagnostic imaging , Ectopia Cordis/diagnostic imaging , Encephalocele/diagnostic imaging , Hernia, Umbilical/diagnostic imaging , Limb Deformities, Congenital/diagnostic imaging , Thoracic Wall/abnormalities , Abnormalities, Multiple/pathology , Abortion, Eugenic , Adult , Amniotic Band Syndrome/pathology , Craniofacial Abnormalities/pathology , Ectopia Cordis/pathology , Encephalocele/pathology , Female , Fetus/pathology , Hernia, Umbilical/pathology , Humans , Karyotyping , Limb Deformities, Congenital/pathology , Pregnancy , Pregnancy Trimester, Second , Thoracic Wall/pathology , Ultrasonography
2.
Clin Genet ; 85(4): 318-27, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23656349

ABSTRACT

NF1 mutations are the underlying cause of neurofibromatosis type 1 (NF1), a neuro-cardio-facio-cutaneous syndrome (NCFC). Because of the clinical overlap between NCFCs, genetic analysis of NF1 is necessary to confirm a clinical diagnosis NF1. This report describes the clinical and genetic findings of 18 years of NF1 molecular diagnostics in the Netherlands. A pathogenic mutation was found in 59.3% (1178/1985) of the index patients, mostly de novo (73.8%). The majority of the index patients (64.3%) fulfilled the National Institute of Health NF1 criteria, a pathogenic mutation was found in 80.9% of these patients. Seventy-four percent of the index patients with an NF1 pathogenic mutation and not fulfilling the NF1 criteria is <12 years, in agreement with the fact that some NF1 symptoms appear after puberty. Genotype-phenotype correlations were studied for 527 index patients. NF1 patients with a type 1 microdeletion have a sixfold higher risk of special education vs NF1 patients with an intragenic mutation. No evidently milder NF1 phenotype for patients with a missense mutation was observed. Forty-six prenatal analyses were performed in 28 (2.4%) families, of which 29 (63%) showed heterozygosity for the familial pathogenic mutation. This indicates that there is a need for prenatal NF1 testing.


Subject(s)
Mutation , Neurofibromatosis 1/diagnosis , Neurofibromatosis 1/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , DNA Mutational Analysis , Female , Genetic Association Studies , Humans , Infant , Male , Middle Aged , Netherlands , Neurofibromatosis 1/etiology , Neurofibromin 1/genetics , Pedigree , Young Adult
3.
Mol Syndromol ; 4(1-2): 20-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-23653573

ABSTRACT

Copy number variations (CNVs), either DNA gains or losses, have been found at common regions throughout the human genome. Most CNVs neither have a pathogenic significance nor result in disease-related phenotypes but, instead, reflect the normal population variance. However, larger CNVs, which often arise de novo, are frequently associated with human disease. A genetic contribution has long been suspected in VACTERL (Vertebral, Anal, Cardiac, TracheoEsophageal fistula, Renal and Limb anomalies) association. The anomalies observed in this association overlap with several monogenetic conditions associated with mutations in specific genes, e.g. Townes Brocks (SALL1), Feingold syndrome (MYCN) or Fanconi anemia. So far VACTERL association has typically been considered a diagnosis of exclusion. Identifying recurrent or de novo genomic variations in individuals with VACTERL association could make it easier to distinguish VACTERL association from other syndromes and could provide insight into disease mechanisms. Sporadically, de novo CNVs associated with VACTERL are described in literature. In addition to this literature review of genomic variation in published VACTERL association patients, we describe CNVs present in 68 VACTERL association patients collected in our institution. De novo variations (>30 kb) are absent in our VACTERL association cohort. However, we identified recurrent rare CNVs which, although inherited, could point to mechanisms or biological processes contributing to this constellation of developmental defects.

4.
Mol Syndromol ; 4(3): 107-13, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23653581

ABSTRACT

The lymphedema-lymphangiectasia-intellectual disability (Hennekam) syndrome (HS) is characterised by a widespread congenital lymph vessel dysplasia manifesting as congenital lymphedema of the limbs and intestinal lymphangiectasia, accompanied by unusual facial morphology, variable intellectual disabilities and infrequently malformations. The syndrome is heterogeneous as mutations in the gene CCBE1 have been found responsible for the syndrome in only a subset of patients. We investigated whether it would be possible to predict the presence of a CCBE1 mutation based on phenotype by collecting clinical data of patients diagnosed with HS, with or without a CCBE1 mutation. We report here the results of 13 CCBE1 positive patients, 16 CCBE1 negative patients, who were clinically found to have classical HS, and 8 patients in whom the diagnosis was considered possible, but not certain, and in whom no CCBE1 mutation was identified. We found no statistically significant phenotypic differences between the 2 groups with the clinical HS phenotype, although the degree of lymphatic dysplasia tended to be more pronounced in the mutation positive group. We also screened 158 patients with less widespread and less pronounced forms of lymphatic dysplasia for CCBE1 mutations, and no mutation was detected in this group. Our results suggest that (1) CCBE1 mutations are present only in patients with a likely clinical diagnosis of HS, and not in patients with less marked forms of lymphatic dysplasia, and (2) that there are no major phenotypic differences between HS patients with or without CCBE1 mutations.

6.
Hum Genet ; 99(6): 806-15, 1997 Jun.
Article in English | MEDLINE | ID: mdl-9187678

ABSTRACT

We report an unusual case of a balanced reciprocal translocation with a recombinant chromosome which has arisen from a familial balanced complex translocation. Fluorescence in situ hybridization studies were essential for the identification of the breakpoints. A review of 60 cases of balanced complex translocations (BCT) has revealed three cases similar to ours. Carriers of BCT have a high risk of having spontaneous abortions or a child with an unbalanced karyotype. Certain types of balanced rearrangements involving an insertion can give rise to a simpler balanced translocation as a result of crossover. Our observations support the assumption that the chance that a de novo balanced complex translocation is associated with an abnormal phenotype increases with the number of breakpoints.


Subject(s)
Recombination, Genetic , Translocation, Genetic , Abortion, Habitual/genetics , Adult , Chromosome Banding , Chromosomes, Human, Pair 2 , Female , Humans , In Situ Hybridization, Fluorescence , Infant, Newborn , Infertility, Male/genetics , Karyotyping , Male , Pedigree , Pregnancy
7.
Am J Med Genet ; 65(3): 213-7, 1996 Oct 28.
Article in English | MEDLINE | ID: mdl-9240746

ABSTRACT

A family is described with skeletal abnormalities involving the shoulder, elbow, and hand, in combination with variable cardiac defects including conduction defects and anatomical anomalies. The disorder followed an autosomal dominant pattern of inheritance with apparently full penetrance for the skeletal abnormalities and reduced penetrance for the cardiac defects.


Subject(s)
Heart Defects, Congenital , Limb Deformities, Congenital , Adult , Arrhythmias, Cardiac , Female , Heart Diseases , Humans , Male , Pedigree
8.
Eur J Pediatr ; 155(4): 311-4, 1996 Apr.
Article in English | MEDLINE | ID: mdl-8777926

ABSTRACT

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.


Subject(s)
Aortic Valve Insufficiency/genetics , Bone Diseases, Developmental/genetics , Contracture/genetics , Dwarfism/genetics , Facies , Mitral Valve Insufficiency/genetics , Aortic Valve Insufficiency/diagnostic imaging , Bone Diseases, Developmental/diagnostic imaging , Child , Child, Preschool , Contracture/diagnostic imaging , Diagnosis, Differential , Dwarfism/diagnostic imaging , Female , Foot Deformities, Congenital/diagnostic imaging , Glycosaminoglycans/metabolism , Hand Deformities, Congenital/diagnostic imaging , Humans , Infant , Infant, Newborn , Mitral Valve Insufficiency/diagnostic imaging , Radiography , Syndrome
9.
Clin Genet ; 47(5): 263-6, 1995 May.
Article in English | MEDLINE | ID: mdl-7554353

ABSTRACT

An adult female is described with mild developmental delay, typical facies, dental anomalies, arachnodactyly and camptodactyly. In many respects she resembles four other patients described earlier, but differs in not having multiple pterygia, nor severe mental retardation. We suggest that this entity should be named Haspeslagh syndrome. The differential diagnosis is discussed.


Subject(s)
Abnormalities, Multiple/physiopathology , Intellectual Disability/physiopathology , Abnormalities, Multiple/diagnosis , Adolescent , Adult , Child , Diagnosis, Differential , Female , Humans , Neck/abnormalities , Syndrome , Thyroid Function Tests
10.
Clin Dysmorphol ; 3(4): 351-2, 1994 Oct.
Article in English | MEDLINE | ID: mdl-7894741

ABSTRACT

We report on a woman with unilateral macrosyndactyly of the second and third toes, a local plantar soft tissue lump, and radiographically an abnormal shape of the phalanges of the affected toes. This finding may represent either an isolated macrosyndactyly or an extremely localised form of Proteus syndrome.


Subject(s)
Proteus Syndrome/classification , Syndactyly/classification , Toes/abnormalities , Adult , Child , Cleft Lip/genetics , Cleft Palate/genetics , Diagnosis, Differential , Female , Genetic Counseling , Humans , Male , Proteus Syndrome/diagnosis , Syndactyly/diagnosis
11.
Am J Med Genet ; 44(5): 683-90, 1992 Nov 15.
Article in English | MEDLINE | ID: mdl-1481833

ABSTRACT

We report on 8 Brazilian patients with the oculo-auriculo-vertebral (OAV) complex with associated uncommon anomalies of hydrocephalus, porencephalic cyst, hand abnormalities, terminal/paraxial hemimelia, Klippel-Feil anomaly, Rokitansky sequence, fibrous dysplasia, and dextrocardia. Our patients show that in some instances a definite diagnosis can be difficult within the wide clinical picture of the OAV complex.


Subject(s)
Abnormalities, Multiple , Bone Diseases, Developmental/diagnosis , Adolescent , Adult , Bone Diseases, Developmental/diagnostic imaging , Brazil , Facial Asymmetry/diagnosis , Female , Genitalia, Female/abnormalities , Goldenhar Syndrome/diagnosis , Humans , Klippel-Feil Syndrome/diagnosis , Limb Deformities, Congenital , Male , Phenotype , Radiography
12.
Am J Med Genet ; 42(4): 467-9, 1992 Feb 15.
Article in English | MEDLINE | ID: mdl-1609830

ABSTRACT

We report on a Brazilian girl, born to consanguineous parents and presenting a multiple congenital anomaly (MCA) syndrome, mainly characterized by blepharophimosis, cleft palate, and arachnodactyly. The clinical aspects involving this patient suggest an apparently undescribed "new" autosomal recessive syndrome.


Subject(s)
Abnormalities, Multiple/pathology , Blepharophimosis , Cleft Palate , Marfan Syndrome , Child , Consanguinity , Female , Genes, Recessive , Humans , Psychomotor Disorders , Syndrome
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