Baraitser–Winter, Fryns–Aftimos and cerebrofrontofacial syndrome types 1 and 3 have recently been associated with heterozygous gain-of-function mutations in one of the two ubiquitous cytoplasmic actin-encoding genes ACTB and ACTG1 that encode β- and γ-actins. We present detailed phenotypic descriptions and neuroimaging on 36 patients analyzed by our group and six cases from the literature with a molecularly proven actinopathy (9 ACTG1 and 33 ACTB). The major clinical anomalies are striking dysmorphic facial features with hypertelorism, broad nose with large tip and prominent root, congenital non-myopathic ptosis, ridged metopic suture and arched eyebrows. Iris or retinal coloboma is present in many cases, as is sensorineural deafness. Cleft lip and palate, hallux duplex, congenital heart defects and renal tract anomalies are seen in some cases. Microcephaly may develop with time. Nearly all patients with ACTG1 mutations, and around 60% of those with ACTB mutations have some degree of pachygyria with anteroposterior severity gradient, rarely lissencephaly or neuronal heterotopia. Reduction of shoulder girdle muscle bulk and progressive joint stiffness is common. Early muscular involvement, occasionally with congenital arthrogryposis, may be present. Progressive, severe dystonia was seen in one family. Intellectual disability and epilepsy are variable in severity and largely correlate with CNS anomalies. One patient developed acute lymphocytic leukemia, and another a cutaneous lymphoma, indicating that actinopathies may be cancer-predisposing disorders. Considering the multifaceted role of actins in cell physiology, we hypothesize that some clinical manifestations may be partially mutation specific. Baraitser–Winter cerebrofrontofacial syndrome is our suggested designation for this clinical entity.

Attention deficit disorder (ADHD) is a complex biobehavioral phenotype which affects up to 8% of the general population and often impairs social, academic, and job performance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be responsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (20p11-p12). Five families in which the pattern of inheritance of ADHD appears to be autosomal dominant were studied. Segregation analysis of the traits studied suggested that the best fitting model was a sex-influenced, single gene, Mendelian pattern. Several genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our patient population and those of other investigators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval.

We describe 2 children with severe ptosis, trigonocephaly, broad nasal bridge, and major brain malformation. A total of 8 children have been reported who share most of these findings. Two of the individuals have had identical pericentric inversions involving chromosome 2p12-q14. These cases appear to represent a unique malformation syndrome.

up to 8% of the general population and often impairs social, academic, and job perfor- mance. Its origins are heterogeneous, but a significant genetic component is suggested by family and twin studies. The murine strain, coloboma, displays a spontaneously hyperactive phenotype that is responsive to dextroamphetamine and has been proposed as a genetic model for ADHD. Coloboma is a semi-dominant mutation that is caused by a hemizygous deletion of the SNAP-25 and other genes on mouse chromosome 2q. To test the possibility that the human homolog of the mouse coloboma gene(s) could be re- sponsible for ADHD, we have carried out linkage studies with polymorphic markers in the region syntenic to coloboma (2Opll-p12). Five families in which the pat- tern of inheritance of ADHD appears to be autosomal dominant were studied. Segrega- tion analysis of the traits studied suggested that the best fitting model was a sex-influ- enced, single gene, Mendelian pattern. Sev- eral genetic models were evaluated based on estimates of penetrance, phenocopy rate, and allele frequency derived from our pa- tient population and those of other investi- gators. No significant linkage was detected between the disease locus and markers spanning this chromosome 20 interval.

A family with five members who have variable findings of leuconychia, knuckle pads, hearing loss, and palmoplantar hyperkeratosis is described. The findings in these subjects are compared with those noted in previously reported patients with Bart-Pumphrey syndrome. The range of disorders which include knuckle pads as part of the phenotype is reviewed.

Neurologic abnormalities have been described only once previously in a child with Weissenbacher-Zweymüller syndrome (WZS), a rare skeletal dysplasia, evident neonatally. We report on identical twin male infants with skeletal findings typical of WZS, including small size at birth, proximal limb shortness, mid face hypoplasia, and myopia. In addition, twin B had a parieto occipital encephalocele while twin A had a meningocele at the same location. Twin B has had significant delays in development and hearing loss.

Brothers were affected with severe congenital contractures, multiple cutaneous manifestations of ectodermal dysplasia, cleft lip/palate, and psychomotor and growth impairment. High resolution prometaphase chromosomes were normal. Molecular studies of DNA markers, closely flanking the X-linked hypohidrotic ectodermal dysplasia locus, did not show evidence of a submicroscopic deletion from the Xq12-q13 region. The parents and a normal sister exhibited none of these findings. This constellation of anomalies appears to represent a unique AR or XLR syndrome.

The physical, radiographic, and pathologic findings in 3 new patients with Marden-Walker syndrome (MWS) are compared with those of previously described children with the syndrome. Over 75% of the children with MWS have blepharophimosis, psychomotor retardation, small mouth, micrognathia, kyphosis/scoliosis, and multiple contractures. Minimal diagnostic criteria have yet to be defined attesting to the broad range of variability and potential genetic heterogeneity in this disorder.

The possible utility of Wechsler's Deterioration Index (WDI) in analyzing children's Wechsler Intelligence Scale for Children-Revised (WISC-R) results was explored in this study. Clinical records of children with learning disabilities (LD) and children with attention deficit-hyperactivity disorder (ADHD) were reviewed to determine if the WDI predicted the presence or severity of the disorders. The ages of the children ranged from 6 to 14. In two independent samples of children with LD (n = 35 and n = 26), the WDI did not predict LD status or severity. The LD samples were mostly male--85% and 57%, respectively. However, the WDI scores did significantly distinguish children with ADHD (n = 10) from nondisabled children (n = 10). The results were cross-validated on an independent sample of children with ADHD (n = 17) when compared to non-ADHD children (n = 22) who experienced significant behavioral difficulties. The ADHD samples were also mostly male--90% and 89%, respectively. The WDI classified only 59% of the children with ADHD and 86% of the non-ADHD children correctly. It is recommended that the WDI be considered a developmental index rather than a deterioration index in children. It is also recommended that significant WDI elevation (greater than .20) be considered to raise the question of ADHD, rather than simply yielding a diagnosis of ADHD.

A large frontal bone defect underlying a "V" shaped scar was noted in a newborn male whose mother had an identical "V" shaped scar at the same location in the anterior hairline. Both had hypertelorism and short palpebral fissures. The mother had no radiographic evidence of skull defect and neither mother nor child had other cutaneous or skeletal anomalies. Cranioplasty was performed on the child using the remaining frontal bones with an excellent cosmetic result. Biopsy performed at operation documented scar tissue extending through the dermis and underlain by thickened dura. Mother and child appear to have a variant form of aplasia cutis congenita, an autosomal dominant trait with wide variation in expression.

We describe a child with multiple anomalies and severe retardation with dup 7pter‐p15.1 and del 7q36‐qter as a result of a parental pericentric inversion of chromosome 7. The pericentric inversion was found in family members in 3 generations with 9 liveborn children who had severe anomalies probably associated with imbalances of chromosome 7.

American Journal of Medical GeneticsVolume 41, Issue 3 p. 390-390 Letter to the Editor Reply to Dr. Rivera Dr. Jeanette C. Ramer, Corresponding Author Dr. Jeanette C. Ramer Penn State College of Medicine, University Hospital, Hershey, PA 17033Department of Pediatrics, The Milton S. Hershey Medical Center, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17033Search for more papers by this authorDavid B. Robins, David B. Robins Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorJavad Todighi, Javad Todighi Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorPhilip N. Mowrey, Philip N. Mowrey Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorSaverio Ligato, Saverio Ligato Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorRoger L. Ladda, Roger L. Ladda Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this author Dr. Jeanette C. Ramer, Corresponding Author Dr. Jeanette C. Ramer Penn State College of Medicine, University Hospital, Hershey, PA 17033Department of Pediatrics, The Milton S. Hershey Medical Center, Penn State College of Medicine, P.O. Box 850, Hershey, PA 17033Search for more papers by this authorDavid B. Robins, David B. Robins Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorJavad Todighi, Javad Todighi Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorPhilip N. Mowrey, Philip N. Mowrey Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorSaverio Ligato, Saverio Ligato Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this authorRoger L. Ladda, Roger L. Ladda Penn State College of Medicine, University Hospital, Hershey, PA 17033Search for more papers by this author First published: 1 December 1991 https://doi.org/10.1002/ajmg.1320410324AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL No abstract is available for this article. Volume41, Issue31 December 1991Pages 390-390 RelatedInformation

Five matings to a dir ins (6;2)(q16;q31q33) carrier have produced a high frequency (42%) of offspring with unbalanced karyotypes. Five children have the derivative chromosome 2 resulting in del (2)(q31q33) and one individual received the derivative chromosome 6 leading to dup (2)(q31q33). The findings associated with the deletion include pre- and postnatal growth retardation, developmental delay, minor facial anomalies, seizures, complex structural heart defects, and limb deficiency. Autopsy of one individual showed complex brain malformations including hydrocephalus secondary to obstruction of the foramina of Monro, extensive heterotopias and polymicrogyria, and an unusual form of total anomalous pulmonary venous return. We compare the findings in these children to those of previously reported cases and construct an overview of the range of anomalies. Apparently, no other individual with dup (2)(q31q33) has been described. We compare the physical peculiarities of our patient with those of individuals with duplications of overlapping regions of 2q.

We report an infant with del(2)(q31q33). His phenotype is compared with those of the 7 children reported previously with the apparently identical deletion. Nine cases of deletions involving other segments of chromosome 2q are reviewed. Common manifestations of the 2 groups include small size at birth, growth and developmental retardation, cardiovascular malformation, microcephaly, and cleft palate.

Sibs with virtually identical humero-radial synostosis (HRS) are presented and compared with 17 previously reported cases from the literature of recessively transmitted HRS. The range of anomalies described includes (in addition to humero-radial synostosis) ulnar hypoplasia, patellar hypoplasia, and chronic glomerulo-nephritis.

Del(3)(p25pter) is associated with a characteristic multiple congenital anomalies/mental retardation syndrome. Early recognition of these manifestations and identification of the chromosome defect are essential for proper management and counseling.

The longitudinal course of two sisters with multiple pterygium syndrome is reported. The findings in these siblings are compared with those of 27 children described in the medical literature. The longitudinal course of short stature, scoliosis, talipes equinovarus, pterygia, hearing loss, and pubertal and intellectual development in this syndrome is described. Recommendations are made for a multidisciplinary approach to individuals with multiple pterygium syndrome, which includes the services of a primary care physician, orthopedist, physical therapist, and plastic surgeon.

Twenty-four children with behavioral problems were hospitalized for four days for intensive enhancement of their parents' parenting skills and a behavior modification program. This method was employed as an alternative approach to an ongoing problem. A questionnaire was designed to gauge parent satisfaction with the results. Seventeen children were rated as having improved behavior from four to 36 months after discharge. A standard behavioral checklist was employed before hospitalization (nine patients) and after hospitalization (19 patients) as a measure to document progress in the whole group. There was significant improvement for total disturbed behavior and a decrease on the anxiety scale with a follow-up period of four to 36 months. We conclude that short-term hospitalization is highly successful for carefully selected children with behavioral problems.