We report on six infants with a neonatally lethal malformation syndrome of hypothalamic hamartoblastoma, postaxial polydactyly, and imperforate anus. Some, but not all, patients had laryngeal cleft, abnormal lung lobulation, renal agenesis and/or renal dysplasia, short 4th metacarpals, nail dysplasia, multiple buccal frenula, hypoadrenalism, microphallus, congenital heart defect, and intrauterine growth retardation. The infants also had hypopituitarism and hypoadrenalism. All were sporadic cases, parents were not consanguineous, chromosomes were apparently normal. Family histories were unremarkable. There was insecticide and/or herbicide exposure in several of the cases, but no exposures were common to all 6 mothers. Five of the patients were born within an 8-month period, but all in different geographic locations. It is postulated that this is a previously apparently unreported syndrome of presently unknown cause.

Nineteen of 421 white children in Montreal schools for the deaf had preauricular pits. The branchio-oto-renal (BOR syndrome was identified in four of the nine families who agreed to family investigation, including audiograms and intravenous pyelograms (IVPs) and may have been present in several others. The penetrance of this autosomal dominant syndrome appears to be high. It is estimated that severe renal dysplasia occurs in about 6% of heterozygotes. The presence of a preauricular pit at birth suggests that the child has at least one chance in 200 of severe hearing loss, and this warrants a careful family history, as well as alertness for any signs of hearing impairment. Offspring of affected individuals are eligible for parental diagnosis of renal dysplasia.

We have evaluated 19 children who were exposed to valproic acid (VPA) in utero to look for manifestations of a fetal valproate syndrome (FVS), as proposed by Di Liberti et al. [1984]. We found no consistent alterations of pre- or postnatal growth with exposure to VPA monotherapy. Postnatal growth deficiency and microcephaly were present however, in two thirds of children exposed to VPA in combination with other anticonvulsants. Developmental delay or neurologic abnormality was found in 71% of those exposed to VPA monotherapy, and in 90% of those exposed to VPA and other anticonvulsants. Craniofacial anomalies, which can be seen with other anticonvulsant exposures, including midface hypoplasia, short nose with a broad and/or flat bridge, epicanthal folds, minor abnormalities of the ear, philtrum or lip, and micrognathia were also found in infants whose mothers used VPA. Prominent metopic ridge and outer orbital ridge deficiency or bifrontal narrowing and certain major anomalies such as tracheomalacia, talipes equinovarus (with intact spine) and lumbosacral meningomyelocele seem to be peculiar to infants with VPA exposure. Other defects such as urogenital anomalies, inguinal or umbilical hernias, and minor digital anomalies that are common to other prenatal anticonvulsant exposures are also occasionally found in those exposed to VPA. Heart defects have been found in infants exposed to nearly every class of anticonvulsant although the types of defects associated with maternal VPA use may be clarified when classified by pathogenetic mechanism. Our findings overall are in agreement with the report of Di Liberti et al. [1984].

Thirty-five subjects with perfect pitch, representing 19 families, were studied with a Perfect Pitch Questionnaire, which provided information on note-recognition capacity and musical exposure and training, as well as demographic characteristics. Perfect pitch was found to predominate in females and was detected at a very early age. The significant family incidence of the trait suggests the operation of genetic mechanisms concerning which speculations are presented.

We have studied 32 unrelated families with a site-specific reciprocal translocation between chromosomes 11 and 22 [t(11;22) (q23;q11)]. In translocation heterozygotes 3:1 meiotic segregation occurs and results in abnormal progeny who carry the der(22) as a supernumerary chromosome. Phenotypic findings consistent with 47,XX (or XY), +der(22), t(11;22) include mental retardation, preauricular skin tag and/or sinus, ear anomaly, palate anomaly, micrognathia, congenital heart disease, and genital anomalies in males. The frequency of abortions among offspring of male and female heterozygotes is increased. Segregation analysis shows that the risk of unbalanced offspring to be born to female heterozygotes may be as high as 10%, and that there may be a significant risk to male heterozygotes as well. The overall carrier frequency among progeny of 11;22 translocation carriers is 70.6%. The occurrence of multiple 11;22 translocation events is supported by de novo occurrence of translocation, familial heteromorphic variants of the der(22), and varied racial and ethnic backgrounds of the families. To our knowledge, with the exclusion of centric fusion translocations, this represents the only example of nonrandom exchange in a constitutional chromosomal rearrangement.