Cardio-facio cutaneous syndrome: neurological manifestations

Cardio-facio-cutaneous (CFC) syndrome is a not uncommon syndrome with a characteristic face, mental retardation, abnormal skin and hair and congenital heart disease. We report the 16th case of this syndrome and give details of the spectrum of neurological manifestations in the cases so far reported.     

Duplication 18q syndrome

Some variation in the phenotype of patients with dup(18q) is recognized. Our patient has the phenotype described for dup(18qter).     

Editorial comment on the paper by Czeizel and Kovács on congenital diaphragmatic defects

Three patients with duplication of 3q regions ranging from 3q25→qter to the entire long arm provide additional documentation of the dup(3q) malformation syndrome. Data on 40 cases now reported define a characteristic face with hirsutism, synophrys, broad nasal root, anteverted nares, downturned corners of the mouth, micrognathia, and malformed ears recognizable even in the 30-week fetus and distinct from that of the Brachmann-de Lange syndrome. Other characteristic anomalies include congenital heart anomalies involving primarily septal defects, hand malformations including simian creases, abnormal dermatoglyphics, clinodactyly or camptodactyly, omphalocele, skeletal anomalies, and genitourinary malformations. Severe mental and growth retardation are common in those patients (64%) who survive the first year. Chromosome study of relatives is extremely important for counseling because only 10 of 40 cases represented de novo duplications.     

Pathologic findings in the Wolf-Hirschhorn (4p-) syndrome

We describe a 1-month-old female with the Wolf-Hirschhorn syndrome. GTG-banding studies disclosed a 46,XX,del(4)(:p15 → qter) in the child and apparently normal chromosomes in the parents. Autopsy at 4 months showed hypoplasia of most organs.     

Trisomy 16p in a liveborn infant and review of trisomy 16p

We report on an infant boy with duplication of part of 16p and partial deficiency of 9p:46.XY, ?9, + der(9)t(9;16)(p24;p13.1)mat. The child has the typical phenotype of dup(16p) even though the extra piece of 16p is small (16pl3.1→pter). Manifestations include severe developmental delay, rounded face, sparse hair, ear anomalies, hypertelorism, cleft soft palate, a thin vermilion border of the upper lip, and left renal dysgenesis. We review 16p duplications.     

Dandy-Walker (like) malformation,atrio-ventricular septal defect and a similar pattern of minor anomalies in 2 sisters: A new syndrome?

We report on sisters with similar craniofacial anomalies, a brain malformation in the area of the posterior fossa, and a congenital heart defect. The craniofacial findings include macrocephaly, a prominent forehead and occiput, foramina pari-etalia, hypertelorism, downslanting palpebral fissures, a depressed nasal bridge, narrow palate, and apparently low-set ears. Patient 1 had a Dandy-Walker malformation with communicating hydrocephalus, aplasia of the posterior portion of the cerebellar vermis, and high insertion of the confluent sinus, while in patient 2, a Dandy-Walker variant was found with aplasia of the cerebellar vermis and hypo-plasia of the hemispheres, large cisterna magna, high insertion of the confluent sinus, but no hydrocephalus. Both sibs were moderately mentally retarded. The older sister had a complete atrio-ventricular canal and died after unsuccessful heart operation at 31/2 years. The younger had a successful operation on a cleft mitral valve and septum primum defect. Chromosomes were normal. The occur-rence of a distinct and similar pattern of congenital anomalies in sisters born to healthy parents points toward a “new” syndrome caused by the homozygous state of an autosomal recessive gene.     

New multiple congenital anomalies/mental retardation syndrome with cardio-facio-cutaneous involvement—the CFC syndrome

Eight patients (4 males, 4 females) were affected with a previously undefined multiple congenital anomalies/mental retardation syndrome which was designated the Cardio-Facio-Cutaneous (CFC) syndrome and which includes congenital heart defects, characteristic facial appearance, ectodermal abnormalities, and growth failure. Cardiac defects were variable, the most common being pulmonic stenosis and atrial septal defect. Typical facial characteristics were high forehead with bitemporal constriction, hypoplasia of supraorbital ridges, antimongoloid slant of palpebral fissures, depressed bridge of nose, and posteriorly angulated ears with prominent helices. The hair was usually sparse and friable. Skin changes varied from patchy hyperkeratosis to a severe generalized ichthyosis-like condition. All cases were sporadic in occurrence, there was no family history of consanguinity, and chromosomes were normal. Although presumed to be genetic, the cause of the CFC syndrome remains unknown.     

Cohen syndrome: Further delineation and inheritance

Four sibs, 2 males and 2 females, were found to have the Cohen syndrome. All had moderate mental retardation, microcephaly, hypotonia, and narrow hands and feet with elongated fingers and toes; 3 were short of stature (2.0–3.5 SD below the mean) with weight between 10th and 50th centile and truncal obesity. Most of the facial characteristics of the syndrome were present: exotropia, prominent ears, short philtrum, and high nasal bridge. Each manifestation varied in severity from one sib to the other. The younger girl also had rheumatoid arthritis. Mild delay of puberty was described in 3 of the sibs. However, one of them has delivered a male infant with normal appearance whose psychomotor development has been normal (as of 9 months). No endocrine problems were documented in the sibship. All patients had normal chromosomes. The data on this sibship support the hypothesis of autosomal recessive inheritance of the Cohen syndrome. Microcephaly and short stature should be stressed as frequent manifestations of the syndrome. The variable expressivity, even among sibs, may be responsible for the paucity of reports on the mildest froms of the Cohen syndrome.     

Duplication of distal 19q: Clinical report and review

We report on a 20-month-old boy with duplication of the distal part of 19q. His karyotype is 46, XY, ?22, + der(22), t(19;22) (q13.3; p11.2)mat. The propositus has multiple minor anomalies, congenital heart defects, seizures, profound psychomotor retardation, and growth impairment. These characteristics are similar to those in the other 10 reported cases of distal 19q duplication and help delineate the phenotype. A review of the literature is presented.     

Hallux duplication,postaxial polydactyly,absence of the corpus callosum,severe mental retardation,and additional anomalies in two unrelated patients: A new syndrome

Two unrelated patients, a 4-year-old boy and a 2 1/2-year-old girl, presented with a similar pattern of abnormalities. Both had severe mental retardation, macrocephaly, absence of the corpus callosum, unusual facial appearance, duplication of hallucal phalanges, postaxial hexadactyly of finger phalanges, and 2/3-syndactyly of toes. The boy also had postaxial hexadactyly of toe phalanges, inguinal hernias and umbilical hernia, and growth retardation. We suspect a common cause of this apparently “new” syndrome, most likely a gene mutation.     

The Noonan-CFC controversy

The Noonan syndrome and the cardio-facio-cutaneous (CFC) syndrome have been described as phenotypically and genetically distinct entities. However, the resemblance between them led some authors to question the validity of this separation. We review available clinical evidence to support the opposite view, namely, that the Noonan and CFC syndromes are indeed distinct and separate conditions, both falling within the broad and causally heterogeneous spectrum of the Noonan/congenital lymphedema phenotype.     

Duplication 10p in a girl due to a maternal translocation t(10;14) (p11:p12)

We present a dup (10p) due to a t(10;14) (p11;p12)mat with a malformation syndrome in a girl. The analysis of 37 published cases shows that 31 patients (16 ♂; 15 ♀) had either a mother or a father carrying a balanced translocation; one case was due to a paternal and another due to a maternal pericentric inversion; two cases were due to de novo translocations; one case had a partial duplication of 10p; and one case had a supernumerary ring chromosome composed of 10p material. The phenotypic spectrum of the condition was analyzed. It is a specific multiple congenital anomalies/mental retardation (MCA/MR) syndrome which includes characteristic facial appearance (dolichocephaly, frontal bossing, short nose with a broad root, highly arched and upswept eyebrows, long philtrum, and thin lips), postnatal growth retardation, severe mental and psychomotor retardation, and several major and minor anomalies. Pseudohermaphroditism seems to be an important anomaly being present in 15 to 20% of affected males. A hypothenar crease together with a transverse crease forming a “crease triangle” seems a helpful sign in the clinical diagnosis of duplication 10p.     

Duplication 8p syndrome: Studies in a family with a reciprocal translocation between chromosomes 8 and 12

We report a family in which six individuals were carriers of a translocation between chromosomes 8 and 12. The balanced carriers had a chromosome constitution: 46,XX or 46,XY,t(8;12)(021;p13). Six individuals in five generations were mentally retarded. Three of them were examined; their chromosome constitution was 46,XX or 46,XY,der(12),t(8;12)(p21;p13); thus they had a duplication of 8pter→8p21 and possible deficiency of 12pter→12p13. The activities of the enzymes that are coded by genes on 8p (glutathione reductase, GSR, E.C. 1.6.4.2.) and 12p (triosephosphate isomerase, TPI, E.C. 5.3.1.1.; lactate dehydrogenase-B, LDH-B, E.C. 1.1.1.27.; and glyceraldehyde-3-phosphate dehydrogenase, G3PD, E.C. 1.2.1.12.) were normal in these individuals. These findings helped in interpreting the position of the break points in the respective chromosomes. The phenotypic findings in our patients are discussed. Segregation analysis indicates no significant variation from a 25% recurrence risk for each of the possible genotypes in the offspring of balanced carriers.     

Cohen syndrome: fertility in a female patient

In this report we describe fertility in an adult female with Cohen syndrome. She gave birth to a son, now 1.5 years old, with discrete facial stigmata and slight psychomotor retardation.     

Interstitial deletion of chromosome 2 region in a malformed infant

We describe an infant with a lumber meningomyelocele and other congenital anomalies and a de novo deletion of 2q36 with a nonmosaic karyotype 46,XX,del(2)(q36). © 1993 Wiley-Liss, Inc.     

Familial Brachmann-de Lange syndrome: Further evidence for autosomal dominant inheritance and review of the literature

We report on a mother and daughter with the Brachmann-de Lange syndrome which supports the view that in some families this disorder is due to autosomal dominant inheritance. A review of the literature concerning autosomal and recessive inheritance of this syndrome is presented. © 1993 Wiley-Liss, Inc.     

Duplication of 16p from insertion of 16p into 16q with subsequent duplication due to crossing over within the inserted segment

Two members of a large family had a similar multiple congenital anomalies mental retardation (MCA/MR) syndrome and an identical aberration of chromosome 16. Their mothers, who are first cousins, had a different abnormality of one chromosome 16, which appeared to be an acrocentric. We interpret these findings as an insertion of a segment of 16p into 16q, following a three-break rearrangement and meiotic crossing over. The two abnormal children have a duplication of 16p11→p13. The clinical manifestations of these patients differ from those of previously reported cases of dup(16p).     

Megalocornea-mental retardation syndrome: An additional case

Oral-facial-digital syndromes (OFDS) constitute a heterogeneous group of entities whose clinical manifestations are often overlapping. We report on a 23-week-old aborted fetus who showed a transitional phenotype between OFD II and OFD VI syndromes. © 1994 Wiley-Liss, Inc.     

Adults with Williams-Beuren syndrome: evaluation of the medical, psychological and behavioral aspects

In order to evaluate the medical, psychological and behavioral aspects of Williams-Beuren syndrome in adulthood, data were collected on 11 patients aged 17 to 66 years. The medical data did not confirm previous reports of significant morbidity. All adults were found to have a moderate or severe degree of mental handicap. They showed the same psychological profile as found in children: good verbal abilities, poor motor abilities, problems with sequencing and with performance tasks. The adults we evaluated showed little disturbing behavior in comparison to other mentally retarded subjects. They achieved a good level of autonomy. The majority lived at home with one or both parents and attended a day centre.