LINC-16. MEDULLOBLASTOMA IN A BOY WITH RUBINSTEIN-TAYBI SYNDROME: A CASE REPORT

BACKGROUND Rubinstein–Taybi syndrome (RTS) is characterized by multiple congenital anomalies and associated with mutations in CREBBP (70%) and EP300 (5–10%). Previous reports have suggested an increased incidence of benign and possibly also malignant tumors, but the correlation remains unclear. Here we present a case of a patient with RTS and medulloblastoma. CLINICAL CASE: A 5-year-old male presented with increased intracranial pressure. An MRI revealed a 4.2 x 4.7 cm mass in the midline of cerebellum arising from the floor of 4th ventricle. The patient underwent a complete resection and pathology revealed medulloblastoma, classic histology. Staging established no disseminated disease. At diagnosis, a peculiar phenotype consisting in mild mental retardation, microcephaly, down-slanting palpebral fissures, broad nasal bridge, highly arched palate, mild micrognathia, screwdriver incisors and wide thumbs and toes was noted. Clinical genetics evaluation was consistent with RTS. Karyotype was performed and normal. Further genetics testing was not done. Treatment consisted in 8 cycles of chemotherapy and craniospinal radiation (2300 cGy to spine, 5500 cGy Total). At the end of treatment, there was no evidence of disease. He was under surveillance for 33 months free of disease, but relapsed with a supratentorial meningeal disease that ultimately resulted in death. CONCLUSION This report highlights the fact that pediatric medulloblastoma can be associated to RTS, in this case associated to classical histology and recurrent disease.

A rare case of combined immunodeficiency due to a deletion of 11(q) – Jacobsen syndrome

Jacobsen syndrome (JS) is a rare combined immunodeficiency caused by partial deletion of the long arm of chromosome 11. Clinical features include physical growth retardation, psychomotor retardation, characteristic facial dysmorphism (skull deformities, hypertelorism, ptosis, coloboma, epicanthal folds, broad nasal bridge, short nose, v-shaped mouth, small low set ears). Patients commonly have malformations of the heart, kidney, gastrointestinal tract, genitalia, central nervous system and skeleton. Abnormal platelet function and immunological problems are usually present. Here we describe a patient with deletion of 11(q) chromosome resulting in clinical phenotype of the facial dysmorphisms, congenital malformations, neurological symptoms, as well as clinical and laboratory features of immunodeficiency. Features of immune dysregulation in a patient with JS are clearly characterized. Patient's parents agreed to use personal dats and photos in research and publications.

Recurrent spontaneous intracranial hemorrhage in a patient with Jacobsen syndrome

Jacobsen syndrome (JS) is an 11q terminal deletion disorder. Affected individuals have developmental delay, cognitive impairment, heart defects, hypertelorism, broad nasal bridge, and a thin upper lip. Most patients with JS have Paris-Trousseau syndrome (PTS), which is characterized by neonatal thrombocytopenia and persistent platelet dysfunction due to 11q terminal deletion including FLI-I gene causing platelet alpha-granule abnormalities.1

You “Cantu”: Multidisciplinary Collaboration Resulting in Successful Orthognathic Surgery

Cantú syndrome (CS) is a rare autosomal dominant disorder caused by a heterozygous pathogenic variant in the ABCC9 or KCNJ8 gene. The disorder is characterized by congenital generalized hypertrichosis, coarse acromegaloid facial features (broad nasal bridge, epicanthal folds, wide mouth, macroglossia), skeletal abnormalities (calvarial thickening, metaphyseal flares, coxa valga, scoliosis), tortuous vasculature (meningeal arteriovenous malformations), and cardiac abnormalities (patent ductus arteriosus, pericardial effusion). Despite the constellation of craniofacial features, there are currently no documented cases of a patient with CS having orthognathic surgery. The purpose of this report is to highlight the multidisciplinary collaboration, including establishment of a genetic diagnosis, cardiac management, and orthodontic therapy, in performing successful orthognathic surgery in a patient with CS.

Partial trisomy 15: a rare occurrence

Partial trisomy 15q is a very rare entity and most of them are characterized by duplication of regions 15q21-15q26.3. This duplication is frequently associated with deletions in another chromosome resulting in unbalanced translocations. Authors report here, a rare case of partial trisomy 15, with breakpoints between 15q11.1 to q23, probably the first reported case with these breakpoints. Irrespective of the breakpoints, the phenotypic features are consistent in all affected cases and predominantly consist of craniofacial anomalies. In addition, finger abnormalities, very short neck, skeletal malformations and congenital heart disease may be present. Our neonate had typical dysmorphic features of arachnocamptodactyly, narrow face, large prominent, nose with broad nasal bridge, long philtrum, pointed chin, short neck, and low set deformed ears. Neonates’ cytogenetic analysis revealed additional chromosomal material on the long arm of the chromosome 15 from q11.1 to q23.1, which was suggestive of partial trisomy of chromosome 15. Most cases reported have had a stormy clinical course, however, our proband had only mild respiratory distress at birth and she was discharged in a few days.

Partial deletion of the long arm of chromosome 7: a case report

Study advances with a childhood case of partial deletion of the long arm of chromosome 7. The patient is a 36-month-old girl with growth retardation, mild mental retardation and delayed bone age. She showed no signs of hypotelorism, upslanting palpebral fissures, epicanthal folds, low-set ears, or flat and broad nasal bridge. Microarray testing using the Affymetrix CytoScan HD array revealed an approximately 58 kb deletion at 7q31.1 in the girl and her father, suggesting paternal origin. As the patient had no characteristic facial features, 7q deletions had not been considered. This case broadens the range of case presentations for microdeletions of chromosome 7.

P.074 Myopathic aspects of Mowat-Wilson Syndrome

Background: Mowat-Wilson Syndrome (MWS) is a genetic syndrome (ZEB2, OMIM: 235730) that occurs in 1 in 50000 births. It is characterized by microcephaly, intellectual disability, dysmorphisms (prominent chin, cupped ears, broad nasal bridge) and Hirschsprung’s disease. Although motor delay and hypotonia are common components, a myopathy has not been described in MWS literature. A childhood case with myopathic features prompted further study of this rare disease. Methods: Patients were recruited from the Mowat-Wilson Foundation via email or social media to complete a survey. Results: Thirteen surveys were returned to date. Although 54% of the patients reported motor delay, none of the patients had myopathy investigations. The index patient, presented at 1 year old, with hypotonia and developmental delay. Pregnancy and family history were unremarkable. Investigations revealed high CK levels (range 300 to 500 U/L), EMG confirmed myopathic motor units, and muscle biopsy showed type 1 fibre predominance. Single gene sequencing revealed pathogenic mutations of ZEB2, confirming a diagnosis of MWS. Conclusions: The description of myopathic features expands the spectrum of this rare syndrome and adds to the differential diagnosis of hyperCKemia in early childhood.

A Case of Multiple Spontaneous Keloid Scars

Keloid scars result from an abnormal healing response to cutaneous injury or inflammation that extends beyond the borders of the original wound. Spontaneous keloid scars forming in the absence of any previous trauma or surgical procedure are rare. Certain syndromes have been associated with this phenomenon, and few reports have discussed the evidence of single spontaneous keloid scar, which raises the question whether they are really spontaneous. Here, we present a 27-year-old mentally retarded single female with orbital hypertelorism, broad nasal bridge, repaired cleft lip and high-arched palate who presented with progressive multiple spontaneous keloid scars in different parts of her body which were confirmed histologically by the presence of typical keloidal collagen. This report supports the fact that keloid scars can appear spontaneously and are possibly linked to a genetic factor. Furthermore, it describes a new presentation of spontaneous keloid scars in the form of multiple large lesions in different sites of the body.

Clinical, Cytogenetic, and Biochemical Analyses of a Family with a t(3;13)(q26.2;p11.2): Further Delineation of 3q Duplication Syndrome

Chromosomal abnormalities that result in genomic imbalances are a major cause of congenital and developmental anomalies. Partial duplication of chromosome 3q syndrome is a well-described condition, and the phenotypic manifestations include a characteristic facies, microcephaly, hirsutism, synophrys, broad nasal bridge, congenital heart disease, genitourinary disorders, and mental retardation. Approximately 60%–75% of cases are derived from a balanced translocation. We describe a family with a pure typical partial trisomy 3q syndrome derived from a maternal balanced translocation t(3;13)(q26.2;p11.2). As the chromosomal rearrangement involves the short arm of an acrocentric chromosome, the phenotype corresponds to a pure trisomy 3q26.2-qter syndrome. There are 4 affected individuals and several carriers among three generations. The report of this family is relevant because there are few cases of pure duplication 3q syndrome reported, and the cases described here contribute to define the phenotype associated with the syndrome. Furthermore, we confirmed that the survival until adulthood is possible. This report also identified the presence of glycosaminoglycans in urine in this family, not related to the chromosomal abnormality or the phenotype.