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Most cases with Kabuki syndrome (KS) were reported sporadically. Recently, a few familial cases of KS were reported. This report provides further evidence that the KS is inherited as a dominant trait with variable expressivity. The proposita is an 18-month-old girl with facial findings characteristic of Kabuki syndrome, prominent fingertip-pads, a midsagittal cleft of vertebral body D4, hypotonia, and psychomotor retardation. Her mother had a similar facial appearance, prominent, cup-shaped ears, an abnormal dentition, early breast development, and low-normal intelligence. Because mother and daughter both had evident Kabuki syndrome, we conclude that KS in this family is inherited as a dominant trait. Further family history supports this finding. Microscopic examination of the hair of the proposita shows abnormalities consisting of trichorrhexis nodosa, twisting of the hairshafts, and irregularity of the diameter of the hair, as was described recently in a patient with KS. This could be another occasional finding in this syndrome, but further studies are required. The presence of abnormal hair, nails, and the commonly described tooth abnormalities in KS further suggest ectodermal involvement in this syndrome.

A cytogenetic study of an alveolar soft-part sarcoma, a rare tumor of probably myogenic origin, demonstrated a t(X;17)(p11;q25) as the sole chromosomal abnormality. Dual- and triple-color fluorescence in situ hybridization, performed on metaphase and interphase cells, confirmed the translocation between chromosomes X and 17 and demonstrated that this translocation resulted in loss of 17q25. Involvement of 17q25 has been described in four previously published cases of alveolar soft-part sarcoma, but without further characterization. Compared to our karyotype, it seems that the derivative chromosome 17 observed in the reported cases could also be the result of a t(X;17) with possible loss of the 17q25 band. If so, a 17q25 deletion and/or chromosome rearrangement between Xp and 17q leading either to a gene fusion or gene disruption could play an important role in the pathogenesis of alveolar soft-part sarcoma.

Prenatal diagnosis of a constitutional interstitial deletion of chromosome 5 (q15q31.1) in a 30-year-old woman is reported. At 21 weeks of pregnancy, routine fetal ultrasounds showed the presence of apparently isolated bilateral club feet. Fetal karyotyping documented an interstitial deletion of the long arm of chromosome 5: 46,XX,del(5) (q15q31) in all 50 analyzed metaphases. Because such deletion is associated with severe psychomotor retardation, the pregnancy was terminated. Postmortem karyotyping of skin fibroblasts confirmed the presence of this interstitial de novo deletion in all mitoses. The breakpoints on 5q were analyzed by fluorescent in situ hybridization and were localized at 5q15 and q31.1. This case illustrates the importance of fetal karyotyping in cases of isolated club feet. At autopsy, the fetus presented had minor anomalies and contractures of knee and hip joints. These clinical findings could fit the diagnosis of congenital contractural arachnodactyly (CCA) or Beals syndrome. CCA is caused by a defect in the fibrillin-2 (FBN2) gene. This gene was previously mapped on 5q23-31. Our molecular studies of both parents and the fetus, using an intragenic polymorphic GT repeat, showed that the FBN2 gene was deleted in the fetus and that the de novo interstitial deletion occurred on the paternally inherited chromosome 5. Thus, CCA may be caused by a loss of function of the FBN2 gene. Clinical findings in this fetus and those of other described cases with interstitial 5q deletions are reviewed, and similarities with CCA are stressed.

Feingold syndrome (or oculodigitoesophagoduodenal syndrome; Microcephaly, Mesobrachyphalangy, Tracheo-esophageal fistula syndrome) is a dominantly inherited combination of hand and foot abnormalities, microcephaly, esophageal/duodenal atresia, short palpebral fissures and learning disabilities, first reported in 1975 (MIM 164280). We report on the seventh family with Feingold syndrome. The propositus is a male infant with esophageal and duodenal atresia, brachymesophalangy of the fifth fingers, bilateral syndactyly of toes 4-5 (and 2-3), relative microcephaly, and facial anomalies. His mother also has microcephaly, similar facial appearance, short fifth fingers with single flexion crease, syndactyly of toes 4-5, and learning disabilities. The maternal sister, brother, and grandmother of the propositus have the same phenotype. The 7 families with Feingold syndrome are reviewed. Intestinal (esophageal/duodenal) atresia/obstruction occurs in approximately 1/3 of the patients with Feingold syndrome.

A boy presented at 5 weeks with a syndrome of pre- and postnatal growth retardation, microcephaly, muscular hypotonia, and facial anomalies resembling those seen in Seckel syndrome or microcephalic primordial dwarfism I. Analysis of prometaphase chromosomes, fluorescent in situ hybridization (FISH), and molecular studies showed the presence of a de novo chromosome 2 deletion that could be defined as del(2)(q33.3q34)pat. Parental chromosomes were normal, except for the presence of a paternal supernumerary marker identified by FISH as der(15). On follow-up of the patient during the next months length development appeared normal and the diagnosis of Seckel syndrome was withdrawn. Clinical findings of previously published cases with interstitial deletion of at least 2q33.3-q34, the deletion present in the propositus, are reviewed and include pre- and postnatal growth retardation, psychomotor retardation, microcephaly, micrognathia, and abnormal/low-set ears; findings also present in the propositus. These findings resemble those described in the Seckel syndrome. Noteworthy is the finding that 2/3 of the 60 reviewed cases originally reported as having Seckel syndrome apparently belong to a heterogeneous group of low birth weight microcephalic dwarfism I yet to be clearly defined. In these patients no chromosome 2q deletion has been reported so far. Retrospective analysis could show if a subgroup of these patients carry submicroscopic deletions at 2q33.3-q34. Alternatively, molecular analysis of this region may be warranted in newly diagnosed patients with Seckel syndrome-like manifestations.

We present a 17-month-old boy with the acrocallosal syndrome. He was born to consanguineous parents. Abnormal findings included agenesis of the corpus callosum, a ventricular septal defect (VSD), postaxial polydactyly of fingers, cleft soft palate, intestinal malrotation, large anterior fontanelle, prominent forehead, hypertelorism, epicanthic folds, short nose and mandible and preauricular skin tags, mixed hearing loss, laryngomalacia, and growth and severe motor and mental retardation. A review of previous reports on the acrocallosal syndrome shows considerable clinical variability; minimal diagnostic criteria are proposed. A developmental field defect with disturbance of midline development is suggested.

We have studied a girl with multiple congenital anomalies, growth and mental deficiency, characteristic facial anomalies, cataracts, cerebellar atrophy, and severe hypocholesterolemia. Death occurred at age 7 years. After excluding several syndromes, i.e., peroxisomal disorders, mevalonic acidaemia, and Marinesco-Sjögren syndrome, it is concluded that this girl had severe Smith-Lemli-Opitz Syndrome (SLOS) with exceptionally long survival. This diagnosis was confirmed through assay of 7-dehydrocholesterol in cultured fibroblasts.

We report here the case of a 7-month-old boy who developed anaplastic large cell lymphoma of true histiocytic origin or malignant histiocytosis, with fever, bone and bone marrow infiltration. Usual clinical features were absent. The neoplastic nature of the disease was supported by the presence of clonal chromosomal abnormalities [t(6;8)(p23;p21),der(8)del(8)(q11aq13), der(22) t(11;22) (q13;13)]. Neither B nor T lineage could be demonstrated here. Morphology, ultrastructural analysis, surface antigens expression, and cytogenetics were more specific for the monocyte-macrophage lineage.

Three sibs, a boy and two girls, born to Moroccan consanguineous parents, were affected with a syndrome characterized by brittle hair, mental retardation, short stature, ataxia, and gonadal dysfunction. The hair in these three patients displayed the morphological and biochemical hallmarks of trichothiodystrophy (TTD). Gonadal function tests showed abnormal gonadotropic responses to LHRH, consistent with delayed puberty in the male and ovarian failure in both females. Comparison with previously reported cases of TTD associated with mental retardation suggests genetic heterogeneity, although specific biochemical markers are needed in order to answer this question.

Clinical and morphologic findings in 3 sibs with congenital cutis laxa are presented. A severe urinary malformation in one affected infant is reported in detail. Elevated serum copper concentrations were observed in 2 of the sibs and in the healthy mother. However, the 64Cu uptake of fibroblast cells from tissue culture was not increased. Ultrastructural pathologic findings from skin biopsies have been studied and compared at birth and at age 2 years. The lack of junction between the 2 elastic fiber components was similar. Further evidence for clinical heterogeneity of this disease is stressed.

Severe osteopetrosis was diagnosed in utero in two successive pregnancies resulting from an intermarriage. Hydrocephaly and skeletal hyperdensity were detected at 18 weeks of gestation, and fractures at 24 weeks. We report on extensive ultrasound, radiological, and pathological findings, including those on brain and bone. The markedly reduced number of osteoclasts observed in these sibs and the very early fetal involvement suggest that this form of osteopetrosis might represent a new entity: autosomal recessive lethal osteopetrosis.