Two sisters with Toriello-Carey syndrome

Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, Robin sequence, abnormally shaped ears, cardiac defect, and hypotonia. We describe two Japanese sisters with a Toriello-Carey syndrome whose phenotypes were as severe as reported male cases. The younger sister died suddenly at age 4 months. Our patients with a severe phenotype and possible parental consanguinity suggest autosomal recessive inheritance of Toriello-Carey syndrome.     

Toriello-Carey syndrome with a 6Mb interstitial deletion at 22q12 detected by array CGH

Toriello-Carey syndrome is a rare multiple congenital anomaly syndrome comprising agenesis of the corpus callosum, telecanthus, short palpebral fissures, abnormal ears, Pierre Robin sequence, and cardiac anomaly. Autosomal recessive inheritance has been hypothesized and chromosome abnormalities have been reported. The present case is a girl with agenesis of the corpus callosum, a large cleft palate, telecanthus, hypertelorism, atrial septal defect, ventricular septal defect, and patent ductus arteriosus. A routine karyotype and fluorescence in situ hybridization subtelomeric analysis were normal. Array comparative genomic hybridization (CGH) identified a de novo 6 Mb interstitial deletion at 22q12.1→22q12.2. These findings support recent findings of chromosomal abnormalities in patients with the Toriello-Carey phenotype. We suggest that the clinical features described in some cases with Toriello-Carey syndrome might be due to cryptic chromosomal rearrangements and that array CGH should be considered in any case presenting with clinical features of Toriello-Carey.     

Toriello-Carey syndrome: case report with additional findings

Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, small palpebral fissures, Pierre Robin sequence, abnormal ears, nuchal laxity and cardiac defects. We report on a female patient who has some additional findings including an anteriorly placed anus. This anomaly adds to the list of other midline anomalies seen in this syndrome. We compare the findings to those seen in the Opitz BBBG syndrome, a well-defined syndrome of the midline developmental field. Our patient, having a severe manifestation of complicated congenital heart disease, died in the neonatal period, which argues against the likelihood that this is an X-linked disorder with more severe manifestations in males.     

Further delineation of the Toriello-Carey syndrome: a report of two siblings

Toriello-Carey is a rare multiple malformation/mental retardation syndrome characterized by dysmorphic features, including telecanthus/hypertelorism, short palpebral fissures, a small nose with anteverted nares, malformed ears, and a Pierre Robin sequence. Affected patients also show several other important signs of midline field disruption: agenesis of the corpus callosum, laryngeal anomalies, and congenital heart defects. Hypotonia and developmental delay are present in most reported cases. Autosomal recessive inheritance was proposed, but an X-linked or sex-influenced gene disorder was also suspected. We report on two siblings, a brother and sister, supporting further an autosomal recessive type of inheritance. Both patients had severe clinical presentation with death in early infancy. Besides clinical findings typical for this condition, they showed additional traits, expanding further the phenotypic spectrum. A specific malformation pattern observed in the patients presented and, in the previously reported cases, suggests an early midline developmental field disruption, presumably caused by a developmental regulatory gene mutation.     

Toriello-Carey syndrome associated with respiratory failure and non-mechanical ileus

Toriello-Carey syndrome comprises agenesis of the corpus callosum, telecanthus, small palpebral fissures, Pierre Robin sequence, abnormal ears, and cardiac defects. We report a boy who has some additional findings, including a severe respiratory failure and intestinal dysmotility. The boy died of these two disorders at age 13 months. Histological examination revealed pulmonary immaturity and a defect of smooth muscle cells in the longitudinal muscle coat of the intestinal musculature, both of which might explain some aspects of the pathophysiology of the patient.     

Corpus callosum agenesis, facial anomalies, Robin sequence, and other anomalies: a new autosomal recessive syndrome?

We describe findings in four children, three of whom are sibs, who appear to have the same, previously undescribed multiple congenital anomaly (MCA) syndrome. The main manifestations include agenesis of the corpus callosum, telecanthus, short palpebral fissures, small nose with anteverted nares, Robin sequence, abnormal ears, redundant neck skin, laryngeal anomalies, cardiac defect, short hands, and hypotonia. The presence of this condition in sibs of each sex suggests that autosomal recessive inheritance is the most likely cause.     

Dup(lq)(q42→qter) syndrome: Case report and review of literature

We report on a patient with primordial growth retardation, mental retardation, and minor anomalies (triangular face, open sagittal suture, frontal bossing, telecanthus, upturned nose, micrognathia, and small mouth with downturned corners). The diagnosis of Russell-Silver syndrome (RSS) had been considered but was abandoned when cytogenetic evaluation showed a partial trisomy lq or duplication lq (46,XY,15, + der(15)t(l;15)(q42;qter). Data from another 5 reports of dup(l)(q42→qter) do not allow delineation of a typical syndrome. However, individuals with dup(lq), del(15q), and Russell-Silver syndrome share common manifestations (i.e., low birth weight, growth retardation, triangular face, low set/abnormal ears, micrognathia, renal anomalies). © 1993 Wiley-Liss, Inc.     

Oculoauriculofrontonasal syndrome (OAFNS) in a nine‐month‐old male

We report a nine‐month‐old Caucasian male with features seen in oculoauriculovertebral spectrum (OAVS) and frontonasal dysplasia sequence (FND) born to normal, non‐consanguineous parents and review the literature. His malformations included a left pre‐auricular skin tag, severely hypoplastic right pinna without an external canal, severely everted and hypoplastic left upper eyelid, bilateral cleft lip and palate, bifid broad nasal tip, ocular hypertelorism, micrognathia, hypoplastic mandible, an extra cervical rib on the left, hemivertebrae at T3–4, agenesis of the posterior corpus callosum with a midline lipoma, and an extra renal pelvis. This constellation of anomalies is consistent with the diagnosis of oculoauriculofrontonasal syndrome (OAFNS) which appears to be a distinct condition from either OAVS or FND but with overlapping features. © 2001 Wiley‐Liss, Inc.     

New syndrome?: MCA/MR syndrome with multiple circumferential skin creases

We describe a combination of multiple congenital anomalies, severe psychomotor retardation and symmetrical circumferential skin creases of arms and legs in a 4.5-year-old male. Craniofacial anomalies included: a high forehead, elongated face, bitemporal sparseness of hair, broad eyebrows, blepharophimosis, bilateral microphthalmia and microcornea, severe optic nerve hypoplasia, epicanthic folds, telecanthus, broad nasal bridge, puffy cheeks, microstomia, cleft palate, enamel hypoplasia, micrognathia, microtia with stenotic ear canals and posteriorly angulated ears. Head circumference was on the 10th centile and a CT scan showed dilated lateral ventricles. Intracranial pressure was not increased. Other abnormalities included: short stature, loose skin, hypotonia, pectus excavatum, inguinal and umbilical hernias, severe scoliosis, hypoplastic scrotum, long fingers and overlapping toes. Echocardiography showed tricuspid regurgitation. Chromosomes were apparently normal. Differentiation from “Michelin tire baby syndrome” and amniotic band sequence is discussed. © 1996 Wiley-Liss, Inc.     

Toriello‐Carey syndrome: Case report with additional findings

Toriello‐Carey syndrome comprises agenesis of the corpus callosum, telecanthus, small palpebral fissures, Pierre Robin sequence, abnormal ears, nuchal laxity and cardiac defects. We report on a female patient who has some additional findings including an anteriorly placed anus. This anomaly adds to the list of other midline anomalies seen in this syndrome. We compare the findings to those seen in the Opitz BBBG syndrome, a well‐defined syndrome of the midline developmental field. Our patient, having a severe manifestation of complicated congenital heart disease, died in the neonatal period, which argues against the likelihood that this is an X‐linked disorder with more severe manifestations in males. © 2001 Wiley‐Liss, Inc.     

Methotrexate and misoprostol teratogenicity: further expansion of the clinical manifestations

We describe a boy who was exposed to misoprostol and methotrexate in the first trimester of gestation as a result of a failed medical abortion. He presented with severe growth retardation, skull defects, proptotic eyes, cleft palate, and severe micrognathia. There were bilateral defects of the upper and lower extremities, missing and hypoplastic ribs, and undescended testicles. He had clinical features of pulmonary hypoplasia with severe persistent pulmonary hypertension and remained ventilator-dependent until he expired. An autopsy revealed brain anomalies consistent with arrhinencephaly. Methotrexate is frequently used in conjunction with misoprostol to induce medical abortion, an off-label use as abortifacient. Both of these medications are well-established teratogens and have an X classification during pregnancy. Data from eight patients who were exposed to both medications in the first trimester indicate a significant teratogenic risk to the developing fetus. Reported anomalies include growth retardation, absence or hypoplasia of the frontal bones, craniosynostosis, large fontanelle, ocular hypertelorism, short palpebral fissures, wide nasal bridge, malformed and low-set ears, and micrognathia. Skeletal anomalies are frequent consisting of syndactyly, mesomelic shortening of the forearms, missing ribs, dislocated hips, and talipes equinovarus. The findings in our case are consistent with the pattern of abnormalities that have been reported in the literature. In addition, our patient had severe pulmonary hypoplasia and arrhinencephaly, anomalies that have not been described previously. This case adds to the documentation of the teratogenic effects of methotrexate and misoprostol on the developing fetus.     

Proximal chromosome 8q deletion in a boy with femoral bifurcation and other multiple congenital anomalies

We describe a male infant with intra-uterine growth retardation and multiple congenital anomalies including prominent forehead, broad nasal bridge, hypertelorism, small upturned nose, flat philtrum, micrognathia, cleft hard palate, low-set and posteriorly rotated ears, short neck, micropenis, hypoplastic scrotum with prominent raphe and undescended testes, malformed lower extremities with contractures, bony protruberance of left thigh, bilateral absence of the fibula, bilateral equinovarus deformity with missing 4th toe on the right foot and short second fingers, congenital heart defect, renal anomalies, brain malformation, and bilateral choanal atresia. He was born at term by cesarean section because of breech presentation to a 19-year-old gravida 2 para 1 African-American female who had no prenatal care. He was admitted to the NICU because of low birth weight, respiratory distress, rule out sepsis and multiple congenital anomalies. Birth weight was 1,475 g, birth length was 33.8 cm, and head circumference was 30 cm. He expired at 5.5 weeks of age. The parents declined a request for autopsy. Chromosome analysis on blood showed that his karyotype was 46,XY,del(8)(q11.23q13.3). FISH studies for 22q deletion were normal. Parental karyotypes were normal. There is a paucity of reported patients with this specific chromosome disorder and this boy appears to be severely affected compared with the few published cases. A gene on chromosome 8q may be involved in limb development.     

A case of del(13)(q22) with multiple major congenital anomalies, imperforate anus and penoscrotal transposition.

"13q-"syndrome is known to have widely variable manifestations, including retinoblastoma, mental & growth retardation, malformation of brain & heart, anal atresia, and anomalies of the face and limbs. Here we report a case of del(13)(q22) with multiple major congenital anomalies for the first time in Korea. The patient was born at 36(+4) weeks of pregnancy by caesarian section. Birth weight was 1490g. On examination the following features were noted: - imperforate anus, ambiguous genitalia (bifid scrotum, penoscrotal transposition, hypospadia), syndactyly of toes, absence of thumbs, abnormal facies (dolichocephaly, telecanthus, large low set ears, saddle nose, high arched palate, micrognathia). Neurocranial ultrasonography showed atrophy of the corpus callosum and multiple calcifications. He died at 14 days. Post-mortem autopsy findings showed cholestasis and fatty metamorphosis of liver, abnormal lobulation (Rt:2, Lt:1) and lymphangiectasis of the lung, VSD, ASD, PDA of heart, and acute tubular necrosis of kidney. Cytogenetic studies was confirmed to 46,XY,del(13) (q22) by Giemsa banded chromosomes from peripheral blood lymphocytes.     

Blepharophimosis,hypoplastic radius,hypoplastic left heart,telecanthus, hydronephrosis,fused metacarpals,and “prehensile” halluces: A new syndrome?

We report on the prenatal ultrasound and postnatal findings in an infant born to a healthy, nonconsanguineous couple. The infant had microcephaly, telecanthus, blepharophimosis, cleft palate, micrognathia, abnormally modeled ears, hypoplastic left heart, hypoplastic radii and ulnae with radial subluxation, pseudoarthrotic distal humeri, fused metacarpals, tibial bowing, unusual feet with long halluces, hydronephrosis, patent urachus, abnormal electroencephalogram, and normal karyotype. To our knowledge, this combination of anomalies has not been recognized previously and may represent a new condition. Am. J. Med. Genet. 80:309–313, 1998. © 1998 Wiley-Liss, Inc.     

Agenesis of the corpus callosum with mental retardation and osseous lesions

We report on a patient with agenesis of corpus callosum, mental retardation, and unusual hitherto undescribed bone changes. The latter include multiple Wormian bones, thin ribs, short, straight, laterally tapering clavicles, small iliac bodies, high iliac angles, triangular areas of sclerosis in the iliac bones, minimal metaphyseal irregularity, striated trabecular pattern in some metaphyses, granular ossification pattern of the patellae, hypoplastic distal phalanges, minimal flatness of phalangeal epiphyses, and retarded bone age. This patient represents a new mental retardation syndrome with agenesis of corpus callosum and unusual bone changes. © 1993 Wiley-Liss, Inc.     

Deletion of the short arm of chromosome 3: a case report with necropsy findings.

A male infant with partial deletion of the short arm of chromosome 3 is described. The features this patient shares with six previously reported cases include microcephaly, dolichocephaly, micrognathia, epicanthic folds, ptosis, low set or malformed ears, postaxial polydactyly, and growth or mental retardation or both. In addition, visceral anomalies not previously reported in association with this chromosomal abnormality are described. These characteristics may constitute a recognisable clinical syndrome.     

Bladder exstrophy and extreme genital anomaly in a patient with pure terminal 1q deletion: expansion of phenotypic spectrum

We describe a 5 2/12 years old male patient with a de novo deletion 1q43q44 of approximately 10.4 Mb in size. The boy presented with the classic features of chromosome 1q43q44 deletion syndrome including growth and psychomotor retardation, microcephaly, distinct facial features and various midline defects as agenesis of corpus callosum, cardiac and urogenital anomalies. Fronto-parietal simplified gyral pattern was an additional neuroimaging finding. The urogenital anomalies in our patient were remarkable in form of bladder exstrophy and severe hypogenitalism with a marked hypoplastic scrotum, small sized retractile testis and absent phallus. To the best of our knowledge, bladder exstrophy and absence phallus have not been previously reported in terminal deletion 1q43q44 syndrome. This report provides further evidence of phenotype-genotype correlation and expands the phenotypic spectrum of midline defects described with this syndrome.     

A 26-month-old child with Marden-Walker syndrome and pyloric stenosis

We recently examined a 26-month-old boy with abnormal face, blepharophimosis, hypertelorism, apparently low-set ears, micrognathia, arachnodactyly, talipes equinovarus, and joint contractures. Subsequently he manifested failure to thrive, respiratory infections, and developmental delay. These congenital anomalies and associated findings are consistent with a diagnosis of the Marden-Walker syndrome. He also had mild pyloric stenosis and duodenal bands, not previously reported in this syndrome. This syndrome appears to be an autosomal recessive trait in some families. A summary of findings of the 16 previous published patients is presented.