Adult ; Female ; Foot Deformities, Congenital ; diagnosis ; genetics ; Hand Deformities, Congenital ; diagnosis ; genetics ; Humans ; Male ; Pedigree ; Young Adult

Female ; Hand Deformities, Congenital ; diagnosis ; genetics ; Humans ; Male ; Phenotype ; Syndactyly ; diagnosis ; genetics

Schinzel-Giedion syndrome is a rare autosomal dominant genetic disease and has the clinical features of severe delayed development, unusual facies, and multiple congenital malformations. In this case report, a 14-month-old boy had the clinical manifestations of delayed development, unusual facies (prominent forehead, midface retraction, hypertelorism, low-set ears, upturned nose, and micrognathia), and multiple congenital malformations (including cerebral dysplasia, dislocation of the hip joint, and cryptorchidism). The karyotype analysis and copy number variations showed no abnormalities, and whole exon sequencing showed a de novo heterozygous missense mutation, c.2602G > A (p. D868N), in SETBP1 gene. Therefore, the boy was diagnosed with Schinzel-Giedion syndrome. Myoclonic seizures in this boy were well controlled by sodium valproate treatment, and his language development was also improved after rehabilitation treatment. Clinical physicians should improve their ability to recognize such rare diseases, and Schinzel-Giedion syndrome should be considered for children with unusual facies, delayed development, and multiple malformations. Gene detection may help with the diagnosis of this disease.
Abnormalities, Multiple ; diagnosis ; genetics ; Craniofacial Abnormalities ; diagnosis ; genetics ; Developmental Disabilities ; diagnosis ; Face ; abnormalities ; Hand Deformities, Congenital ; diagnosis ; genetics ; Humans ; Infant ; Intellectual Disability ; diagnosis ; genetics ; Male ; Nails, Malformed ; diagnosis ; genetics

OBJECTIVETo identify genomic aberrations underlying pathogenesis of split hand foot malformation (SHFM) in two Chinese families, and to provide genetic counseling and prenatal diagnosis for them.

METHODSTwo sets of peripheral blood and amniotic fluid samples were collected from the patients. One was processed with routine culture and karyotype analysis. For another set, DNA was extracted and analyzed with array-based comparative genomic hybridization (array-CGH).

RESULTSKaryotype analysis of peripheral blood samples for both probands was normal. Karyotype analysis of the amniotic fluid from family 1 has found no abnormality. However, analysis of amniotic fluid samples from the second family showed del(7)(q21q22.1). By array-CGH analysis, both blood and amniotic fluid samples from the first family showed a 662.3 kb dup(10q24.31q24.32). Array-CGH analysis of the blood sample from the second family was normal, whilst analysis of amniotic fluid sample revealed a 19.97 Mb del(7q11.23q21.3).

CONCLUSIONArray-CGH features high resolution, high accuracy and rapid diagnosis for unbalanced chromosomal aberration. The dup(10q24.31q24.32) and 19.97 Mb del(7q11.23q21.3) have been the cause of SHFM in the two families. Genetic counseling and prenatal diagnosis have been provided for both families in order to prevent this birth defect.

Adult ; Asian Continental Ancestry Group ; genetics ; China ; Chromosome Deletion ; Chromosome Duplication ; Chromosomes, Human, Pair 10 ; genetics ; Chromosomes, Human, Pair 7 ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Foot Deformities, Congenital ; diagnosis ; genetics ; Hand Deformities, Congenital ; diagnosis ; genetics ; Humans ; Infant, Newborn ; Male ; Pedigree ; Pregnancy ; Prenatal Diagnosis

No abstract available.
Bone Diseases, Developmental/diagnosis/drug therapy/*genetics ; Child ; Fibrillin-1/*genetics ; Hand/diagnostic imaging ; Heterozygote ; Human Growth Hormone/therapeutic use ; Humans ; Limb Deformities, Congenital/diagnosis/drug therapy/*genetics ; Male ; Pelvis/diagnostic imaging

PURPOSE: To present a case of Weill-Marchesani syndrome with corneal endothelial dysfunction due to anterior dislocation of a spherophakic lens and corneolenticular contact. METHODS: A 17-year-old woman presented with high myopia and progressive visual disturbance. She was of short stature and had brachydactyly. Her initial Snellen best corrected visual acuity (BCVA) was 20/50 (-sph 20.50 -cyl 3.00 Ax 180) in her right eye and 20/40 (-sph 16.00 -cyl 6.00 Ax 30) in her left eye. Slit lamp examination revealed a dislocated spherophakic lens touching corenal endothelium. A microspherophakic lens, hypoplastic ciliary body, and elongated zonules were confirmed on rotating Scheimpflug camera (Pentacam(R)) and on ultrasound biomicroscopy. Specular microscopy showed corneal endothealial dysfunction. Systemic evaluation was performed, and chromosomal study showed 46, XX, inv (15) (q13qter). The patient was diagnosed with Weill-Marchesani syndrome. RESULTS: Due to impending corneal decompensation, phacoemulsification and suture fixation of the intraocular lens were performed. The operation and postoperative course were uneventful. Three months postoperatively, the visual acuity was 20/30 (OD) and 20/40 (OS) without correction, and BCVA was 20/20 (+sph 0.50 -cyl 2.00 Ax 160 : OD) and 20/25 (+sph 1.50 -cyl 3.00 Ax 30 : OS). During the follow-up period, increased corneal endothelial counts, hexagonality, and decreased corneal thickness were achieved. CONCLUSIONS: In Weill-Marchesani syndrome with a chromosomal anomaly, a dislocated spherophakic lens may cause severe corneal endothelial dysfunction due to corneolenticular contact, and prompt lensectomy is important to prevent such complications.
*Abnormalities, Multiple ; Adolescent ; *Chromosomes, Human, Pair 15 ; Diagnosis, Differential ; Dwarfism/*genetics ; Endothelium, Corneal/pathology/ultrasonography ; Female ; Fingers/*abnormalities ; Hand Deformities, Congenital/diagnosis/*genetics ; Humans ; Inversion, Chromosome/*genetics ; Lens Implantation, Intraocular/methods ; Lens Subluxation/diagnosis/*genetics/surgery ; Microscopy, Acoustic ; Phacoemulsification/methods ; Syndrome