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Townes-Brocks syndrome is an autosomal dominantly inherited disorder, which comprises multiple birth defects including renal, ear, anal, and limb malformations. TBS has been shown to result from mutations in SALL1, a human gene related to the developmental regulator SAL of Drosophila melanogaster. The SALL1 gene product is a zinc finger protein thought to act as a transcription factor. It contains four highly conserved, evenly distributed C2H2 double zinc finger domains. A single C2H2 motif is attached to the second domain, and at the amino terminus SALL1 contains a C2HC motif. Most mutations causing TBS are clustered in the N-terminal third of the SALL1 coding region and result in the production of truncated proteins containing only one or none of the C2H2 domains and the N-terminal transcriptional repressor domain of SALL1. Twenty-three SALL1 mutations were reported prior to this work, 22 of which are located in exon 2, 5' of the second double zinc finger-encoding region. Here we present 12 novel mutations in SALL1 associated with Townes-Brocks syndrome in 13 unrelated families. These include three nonsense mutations, three short insertions and six short deletions. Thus the number of SALL1 mutations increases to 35. Rare phenotypical features among mutation positive patients include hypothyroidism, vaginal aplasia with bifid uterus, cryptorchidism, bifid scrotum without hypospadia scrotalis, unilateral chorioretinal coloboma with loss of vision, dorsal hypoplasia of the corpus callosum, and umbilical hernia.

We describe a girl with an unusual form of ectodermal dysplasia. She was mildly mentally retarded, had normal height, weight, and head circumference, a large scalp defect, a peculiar face with large palpebral fissures, a broad nasal bridge and constantly open mouth, abnormally-modeled ears, syndactyly of fingers/toes, mild hypohidrosis, and severe onychogryposis. Her hair was short, abundant, and stiff, her eyebrows were sparse, and her skin was dry. Analysis of the literature showed that this type of association of ectodermal dysplasia and other defects has not been previously described.

We describe clinical manifestations and historical data on ten patients with Kabuki make-up syndrome. All patients are of European ancestry and all have the characteristics of the syndrome, including typical face, retarded physical development, and mild to moderate mental retardation. Two of the probands have low-normal intelligence. Prominent and broad philtrum was described as an important component manifestation of the syndrome. In three families some clinical manifestations of Kabuki make-up syndrome were observed in parents and some other relatives of the probands in three generations. Some phenotypic differences between Asian and non-Asian patients were noted. The possible cause of the syndrome is discussed. The present observations and a literature review suggest autosomal dominant inheritance with different expressivity of the Kabuki make-up syndrome.

We present three probands with partial trisomies 2p21-23 due to ins(4;2)(q21;p21p23) pat, 2p23-pter due to t(2;4)(p23;q35)mat, and 2p21-pter due to t(2;11)(p21;q23.3)mat. More than 50 cases of partial trisomy 2p have been reviewed and some abnormalities, unusual for most other types of structural autosomal imbalance, have been found in patients with inherited forms of 2p trisomy and in their non-karyotyped sibs. Neural tube defects (anencephaly, occipital encephalocele, and spina bifida) were found in five probands and 4/6 affected non-karyotyped sibs. The only triplicated segment common to all was 2p24. Different forms of "broncho-pulmonary a/hypoplasia" (including two cases of lung agenesis) were described in four patients (overlapping triplicated segment was 2p21-p25). Three patients (with overlapping triplicated segment 2p23-p25) had diaphragmatic hernia. Abnormal rotation of the heart or L-transposition of large vessels (with or without visceral heterotaxia) was found in two infants (overlapping triplicated segment 2p23-p24). In two patients with common triplicated segment 2p22.3-p25, neuroblastoma has been described. The occurrence of all these defects may be explained either by the action of the same gene(s) mapped to 2p24 or by action of some independent factors located in different segments of the short arm. Although the latter hypothesis is much less probable, it can not be rejected at the present time. We propose the existence of a genetic system controlling surveillance of an abnormal embryo to explain the phenotypic differences between patients with the same imbalance within a family. In some "restrictive" combinations the abnormal embryos will die, although in "permissive" combinations they can survive.

Clinico-genetic analysis of 21 personal observations and review of the literature confirmed the existence of a wide phenotypic spectrum of Dubowitz syndrome. It is shown that in spite of marked microcephaly, severe mental deficiency is rare in Dubowitz syndrome and about half of the patients are mentally normal. A "new" clinical subtype is defined, which also includes anorectal anomalies and premature craniosynostosis. All three families with this form are natives of a small area of Byelorussia, suggesting an autosomal or X-linked recessive mode of inheritance of this subtype. The data obtained confirm autosomal recessive inheritance of Dubowitz syndrome.

At least nine cases of holoprosencephaly (HPE) found in patients with confirmed loss of 7q34----7qter or 7q36----7qter have been reported in the literature. In the present report, balanced rearrangements involving chromosome 7q [inv(7)(p22.1q34) and t(4;7)(q31;q36)] were shown in two mothers examined after the birth of their non-karyotyped infants with HPE and hydronephrosis. In both cases, del(7q) was the most probable imbalance. The available data confirm the association between HPE and del(7q). Predominance of cyclopia and cebocephaly, the severest forms of HPE, suggests that del(7q) may be an important factor in arresting prosencephalon development at the earliest stages.