Holoprosencephaly (HPE) is the most common structural anomaly of the human brain and is one of the anomalies seen in patients with deletions and duplications of chromosome 13. On the basis of molecular analysis of a series of patients with hemizygous deletions of the long arm of chromosome 13, we have defined a discrete region in band 13q32 where deletion leads to major developmental anomalies (the 13q32 deletion syndrome). This approximately 1-Mb region lies between markers D135136 and D13S147. Patients in which this region is deleted usually have major congenital malformations, including brain anomalies such as HPE or exencephaly, and digital anomalies such as absent thumbs. We now report that human ZIC2 maps to this critical deletion region and that heterozygous mutations in ZIC2 are associated with HPE. Haploinsufficiency for ZIC2 is likely to cause the brain malformations seen in 13q deletion patients.

We review 43 p atie n ts (15 new, 28 literature) w ith the branchio-oculo-facial (BOF) syn drome, w h ic h has a d istin ctiv e phenotype ran g in g from m ild to severe forms, consist in g of eye, ear, oral, a n d craniofacial anom alies. V irtu a lly u b iq u ito u s and possibly pathognom onic are the cervical/infra-auricu la r sk in defects. M uch less common are supra-auricular defects occurring as iso late d anom alies or w ith cervical defects. Re gardless of lo catio n , these lesions may have aplastic, "hem angiom atous," or otherwise abnorm al overlying skin, and d ra in in g sinus fìstulae. R e n a l m alfo rm atio ns are frequent, b u t congenital h e a rt a n d central nervous system defects are rare* Psychomotor per form ance is u s u a lly norm al, b u t develop m ent delays, h y p o to n ia , and visual, hearing, and speech problem s are common. Autoso m al d o m in a n t in h e rita n c e seems likely. Overlap betw een the B O F and branchio-otorenal syndromes has been observed, b u t elu cidation o f its m o le cu lar basis is not yet available. This article also discusses 5 p a tients w ith aty p ical m anifestations consid ered to be possibly affected or probably u n affected, w ho are sufficiently unusual to be excluded from the fin a l data analysis.

This is the report of two independent families in which a balanced maternal translocation led to trisomy 12 p in one of each their offspring. Evaluation of 21 further case reports indicates that this is a phenotypically well defined syndrome which leads to severe developmental retardation. It can be recognized by a characteristic combination of craniofacial anomalies which are summarized in a phantom picture. The gene sequences which produce the typical features in the trisomic state must be localized distally to band 12p12, which is the breakpoint in the partial trisomies. The specific craniofacial anomalies are not visibly modified by the length of the trisomic segment or additional small monosomies or trisomies of recipient chromosomes. However, the frequency and severity of organ malformations and the resulting probability of survival seem to decrease with increasing degrees of chromosomal imbalance. A cytogenetic classification of the 21 inherited translocations and a segregation analysis from the pedigree data was performed. For the different types of translocations the calculated risk figures are given.

Chromosome analysis in a newborn, the daughter of diabetic parents, who showed multiple dysmorphic signs and malformations revealed direct duplication of a long arm segment of chromosome 3(3q2100 leads to 3q2700). Both parents have normal karyotypes. Compilation of the phenotype stigmata with those of 7 other patients and 1 fetus with partial trisomy 3q confirmed that clinical recognition of this syndrome is possible. It is characterized by hypertrichosis, typical craniofacial dysmorphia, frequent organ malformations and skeletal anomalies, as well as a peculiar dermatoglyphic pattern. It is a severe genetic disturbance, leading to death in the first months of life in many cases and only symptomatic care is advised.

Baumeister FAM, Egger J, Schildhauer MT, Stengel‐Rutkowski S. Ambras syndrome: delineation of a unique hypertrichosis universalis congenita and association with a balanced pericentric inversion (8) (p11.2; q22). Clin Genet 1993: 44: 121–128. © Munksgaard, 1993 Congenital hypertrichosis universalis is a rare autosomal dominant disease. We report the further development of a Greek girl, now aged 3 years, the first case associated with a balanced structural chromosomal aberration. She was described as a neonate by Sigalas et al. (1990). Her persistent generalized hypertrichosis is most excessive on the face, ears and shoulders. Her fine silky hair is of the vellus, not the lanugo type. The syndrome features are characterized, referring to nine further published case reports. It is distinguished from other types of congenital hypertrichoses, which have been described in the literature under different synonyms. To avoid confusion in the terminology, we propose to name this type of hypertrichosis Ambras syndrome in reference to the first documented family with congenital hypertrichosis universalis in the 16th century.