Agenesis of corpus callosum in three sibs

Summary We report on a rare familial cases with complete agenesis of the corpus callosum found in three sibs, in which autosomal recessive mode of inheritance was suggested.     

Two siblings with midline field defects and Hirschsprung disease: Variable expression of Toriello-Carey or new syndrome?

We describe 2 sibs with multiple congenital anomalies. The main manifestations include hypoplasia of the corpus callosum and/or cerebellar hypoplasia, Robin sequence, pharyngeal and laryngeal hypoplasia, abnormal ears, excessive neck skin, cardiac defect, and Hirschsprung disease. The presence in 2 sibs born to healthy, consanguineous parents suggests autosomal recessive inheritance. These anomalies must have arisen during blastogenesis; the syndrome resembles most the condition described in 1988 by Toriello and Carey (Am J Med Genet 31:17–23). © 1993 Wiley-Liss, Inc.     

Toriello-Carey syndrome: Evidence for X-linked inheritance

Toriello-Carey syndrome is characterized by agenesis of the corpus callosum, telecanthus, short palpebral fissures, Robin sequence, abnormal ears, cardiac anomalies, and hypotonia. We describe two patients with Toriello-Carey syndrome and call attention to an unbalanced sex ratio. The first patient, a male, was born at term by Cesarean section and manifests micrognathia, cleft soft palate, hypoplastic right ear, anotia on the left side, cerebellar vermis hypoplasia, hydrocephalus, agenesis of the corpus callosum, and hypoplastic left heart. He died 2 days after birth. The second patient is the male sib of a patient reported previously [Am J Med Genet 42: 374–376; 1992]. He had large fontanelles, telecanthus, a short nose, small and malformed ears, micrognathia, a large ventricular septal defect, and pulmonary stenosis. At age 8 months he has growth retardation and developmental delay. A sister is unaffected. Review documented eight other patients with Toriello-Carey syndrome, six of whom were male. The two female patients are less severely affected and are still alive. Of the other male patients, all are deceased except one who is still alive at age 5 years; he has severe growth retardation (-3 SD), mental retardation (DQ44), severe speech delay, and characteristic anomalies. The predominance of affected males and the milder phenotype in the female patients suggests an X-linked gene or sex influenced gene. © 1996 Wiley-Liss, Inc.     

Craniotelencephalic dysplasia in sisters: Further delineation of a possible syndrome

We describe two sisters with a complex of anomalies involving the cranium and brain. The changes in the former are consistent with those previously described as craniotelencephalic dysplasia and those in the latter indicate primary developmental abnormalities of the central nervous system including septo-optic dysplasia, absent olfactory nerves, agenesis of the corpus callosum, and lissencephaly. Per se, these cerebral malformations are causally heterogeneous, but their occurrence in association with craniotelencephalic dysplasia suggests that this combination is a distinct, probably autosomal recessive, syndrome.     

Acrocallosal syndrome in two African brothers born to consanguineous parents

We describe two mentally retarded brothers with craniofacial anomalies, polydactyly, and other clinical manifestations compatible with the acrocallosal syndrome (ACS). These are the first black patients from Africa with this diagnosis. They are also the fourth set of sibs described with ACS, and together with the parental consanguinity documented in this family, confirm autosomal recessive inheritance of this syndrome. The clinical manifestations in our patients confirm the intrafamilial variability of the syndrome. Postnatal onset of growth retardation is proposed as an additional manifestation of ACS. © 1994 Wiley-Liss, Inc.     

Agenesis of the corpus callosum in a mother and son

Most reported familial cases of agenesis of the corpus callosum have followed either an autosomal recessive or an X-linked recessive pattern of inheritance. To the best of our knowledge, there is only one previous report of a family showing clear-cut autosomal dominant inheritance. We present the second such family, among whom a mother and her son had moderately severe coordination problems and low-normal intelligence. We suggest that agenesis of the corpus callosum, when transmitted as an autosomal dominant trait, is clinically characterized by a relatively milder phenotype than that occurring when inheritance is either autosomal or X-linked recessive and may be more common than has been thought. Am. J. Med. Genet. 69:152–154, 1997. © 1997 Wiley-Liss, Inc.     

“C” Trigonocephaly syndrome: Report of a child with agenesis of the corpus callosum and tetralogy of Fallot,and review

We report on a new case of the Opitz “C” trigonocephaly syndrome. Our patient had agenesis of the corpus callosum, an anomaly seen only twice previously, and tetralogy of Fallot, described only once before. A review shows that a combination of conotruncal heart defects and midline brain anomalies characterizes patients with this entity. © 1995 Wiley-Liss, Inc.     

Diaphragmatic hernia-exomphalos-hypertelorism syndrome: A new case and further evidence of autosomal recessive inheritance

We describe a male patient with wide anterior fontanel and metopic suture, hypertelorism, down slanting palpebral fissures, bilateral iris coloboma, omphalocele, and bilateral absence of the diaphragm with herniation of abdominal organs causing pulmonary hypoplasia and death. Autopsy also showed intestinal malrotation. All findings in this case are consistent with those described as a newly recognized syndrome by Donnai and Barrow [1993]. Since the parents are first cousins, this case provides further evidence for the previously postulated autosomal recessive inheritance pattern. Follow-up on the patients and families reported by Donnai and Barrow [1993] also supports autosomal recessive inheritance. Am. J. Med. Genet. 68:441–444, 1997. © 1997 Wiley-Liss, Inc.     

FG syndrome: Report of three new families with linkage to xq12-q22.1

FG syndrome is a rare X-linked recessive form of mental retardation, first described by Opitz and Kaveggia in 1974 in five related males with mental retardation, disproportionately large heads, imperforate anus, and congenital hypotonia. Partial agenesis of the corpus callosum was noted in at least one of the initial cases and has been seen in a number of subsequently-reported cases. The associated congenital hypotonia with joint hyperlaxity tends to progress to contractures with spasticity and unsteady gait in later life. The presence of subtle facial abnormalities and the characteristic behavior in midchildhood facilitate diagnosis at this age, particularly when there are other affected male relatives in the maternal family. Recently, Briault et al. [1997[ mapped a gene for FG syndrome to the Xq12-q21.31 region. We describe three additional families (six additional patients) with FG syndrome on whom we have conducted linkage analysis. Our findings support the localization of a gene for the FG syndrome in Xq12-q21. In addition, we have noted skewed X-inactivation in carrier females, as well as new associated findings in affected males of sagittal craniosynostosis and split hand malformation. Am. J. Med. Genet. 80:145–156, 1998. © 1998 Wiley-Liss, Inc.     

New case of Bartsocas-Papas syndrome surviving at 20 months

We report on patient with Bartsocas-Papas syndrome surviving at age 20 months. Similar to 7 previously reported families, this patient is of Mediterranean ancestry, pointing to clustering of the responsible mutant gene in Southern Europe. In 3 of the 11 Bartsocas-Papas syndrome patients described so far, including the present case, the condition has not been neonatally lethal. This suggests that about one-fourth of these patients could survive. This information is important for genetic counseling.     

Syndrome of partial aniridia,cerebellar ataxia,and mental retardation—Gillespie syndrome

Here we describe a 5-year-old girl with Gillespie syndrome of cerebellar ataxia, partial aniridia, and mental retardation. The Gillespie syndrome probably is an autosomal recessive trait.     

Neu-Laxova syndrome: report of a case from Turkey

Kuseyri F, Bilge I, Bilgiç L, Apak MY. Neu-Laxova syndrome: report of a case from Turkey.
Clin Genet 1993: 43: 267–269. © Munksgaard, 1993
We describe a case of Neu-Laxova syndrome in a newborn female who was born at full-term to consanguineous Turkish parents. The pathological and radiological features are described.     

Craniosynostosis and kidney malformation in a case of Hennekam syndrome

Hennekam syndrome is a rare autosomal recessive syndrome which was described for the first time in 1989. Here, we present a girl with intestinal lymphangiectasia, severe lymphedema of limbs, seizures, mild mental retardation, and facial anomalies consistent with the diagnosis of Hennekam syndrome. In addition, she had an ectopic kidney and craniosynostosis of the coronal suture, 2 manifestations not previously reported in this syndrome. While the molecular basis of Hennekam syndrome remains, as yet, unknown, this report illustrates its variable clinical expression. © 1995 Wiley-Liss, Inc.     

Delineatino of the da-Silva syndrome

We present a 6-month-old boy with agenesis of the corpus callosum, hypertonicity, severe growth and psychomotor retardation, microcephaly, large prominent ears, and delayed bone age. Similarity of his manifestations to these in 3 sibs described by da-Silva in 1988 suggests initial delineation of the da-Silva syndrome. © 1994 Wiley-Liss, Inc.     

Frontofacionasal dysplasia

We report on the fourth case of frontofacionasal dysplasia and discuss the differential diagnosis of this autosomal recessive disorder.     

Cerebral defects and nephrogenic diabetes insipidus with the ARC syndrome: Additional findings or a new syndrome (ARCC-NDI)?

We report on 4 children from 2 unrelated families who appear to have the lethal ARC syndrome (arthrogryposis, renal tubular dysfunction, and cholestasis) together with the additional findings of nephrogenic diabetes insipidus and cerebral anomalies, including deafness. With increased survival time in our patients, paucity of the intrahepatic bile ductules and cholestasis progressed to cirrhosis, growth was severely impaired, and severe mental retardation became apparent. No evidence was found for peroxisomal, chromosomal, or mitochondrial disorders. We propose to amend the ARC mnemonic to ARCC-NDI (A-Arthrogryposis, R-renal Fanconi, C-cerebral, C-cholestasis, NDI-nephrogenic diabetes insipidus) to name the major manifestations of this syndrome, several of which have not been appreciated. Am. J. Med. Genet. 72:335–338, 1997. © 1997 Wiley-Liss, Inc.     

The Nager syndrome

The Nager syndrome was identified in a newborn infant and in a subsequent sib by prenatal ultrasonography. This report documents an autosomal recessive pattern of inheritance for this disorder.     

New syndrome? Osteochondrodysplasia with rhizomelia,platyspondyly, callosal agenesis,thrombocytopenia, hydrocephalus,and hypertension

A female infant born at term to phenotypically normal nonconsanguinous parents had hypertension, thrombocytopenia, hydrocephalus, callosal agenesis, and nonlethal rhizomelic osteochondrodysplasia. Her osteochondrodysplasia was characterized roentgenographically by shortening and metaphyseal broadening of long bones, without bowing, and by platyspondyly, with deficient ossification of dorsal and central portions of vertebral bodies. By light microscopy, the iliac crest growth plate showed expansion of the zone of chondrocyte hypertrophy and degeneration, with faulty columnar alignment, sparse vascular ingrowth, and irregular mineralization at the zone of chondroosseous transformation. These findings appear to define a novel osteochondrodysplasia, which in association with hypertension, thrombocytopenia, hydrocephalus, and callosal agenesis may constitute a new syndrome.     

Cohen syndrome: the clinical symptoms and stigmata at a young age

We present the clinical findings and follow-up data of four female children with Cohen syndrome, two sisters and one pair of dizygotic female twins. The most characteristic findings from birth on were as follows:

• 1. 

  Low-normal growth parameters at birth.
• 2. 

  Mild hypotonia and evidence of progressive microcephaly with narrow forehead in the first year of life.
• 3. 

  Neutropenia was present from the beginning, remained unchanged over the years and is not associated with higher susceptibility to infections.
• 4. 

  Autistic behavior and severe psychomotor retardation up to the age of 2 years. At that age the ocular anomalies with high-grade myopia and chorioretinal dystrophy were diagnosed. Correction of the myopia resulted in a marked catch-up in psychomotor development.
• 5. 

  After the age of 6 years facial stigmata became more evident with short philtrum of the upper lip and broad and large upper incisors.
• 6. 

  Tendency to truncular obesity with rest hypotonia and poor muscle development after the ages of 6 to 8 years.

The clinical findings and follow-up data in the present four children with Cohen syndrome illustrate that the diagnosis of Cohen syndrome in infancy is very difficult.