BBBG syndrome or Opitz syndrome: new family

We report on a family where the propositus had G syndrome, including laryngeal cleft, and another relative had the facial anomalies typical of the BBB syndrome. We review the literature on the BBB and G syndrome, and argue that no clinical or laboratory criteria permit a differential diagnosis of the two syndromes. Therefore, we suggest that they should be considered variable expression of the same gene. The name BBBG syndrome is proposed for the amalgamated syndrome.     

Platelet dysfunction in a patient with the Opitz (BBBG) syndrome

An 11-year-old girl with Opitz (BBBG) syndrome presented with a bleeding disorder. Studies showed an immune-mediated qualitative platelet dysfunction in the absence of thrombocytopenia. This is the first report of hemostatic dysfunction in a patient with the Opitz (BBBG) syndrome. This report considers the possible relationship of the platelet dysfunction to the Opitz (BBBG) syndrome and its treatment. © 1992 Wiley-Liss, Inc.     

Ring chromosome 22 karyotype in a patient with Opitz (BBBG) syndrome

We report on a patient with hypomelanosis of Ito (HI), developmental delay, recurrent pneumonia, and facial asymmetry. Chromosome analysis done on blood and on one of three skin biopsies showed trisomy 18 mosaicism. This is the first report of HI associated with trisomy 18 mosaicism. This neuroectodermal disorder appears to be a nonspecific manifestation of chromosome mosaicism.     

Platelet dysfunction in a patient with the Opitz (BBBG) syndrome.

An 11-year-old girl with Opitz (BBBG) syndrome presented with a bleeding disorder. Studies showed an immune-mediated qualitative platelet dysfunction in the absence of thrombocytopenia. This is the first report of hemostatic dysfunction in a patient with the Opitz (BBBG) syndrome. This report considers the possible relationship of the platelet dysfunction to the Opitz (BBBG) syndrome and its treatment.     

Opitz BBBG syndrome: new family with late-onset, serious complication

The Opitz BBBG syndrome is characterized by hypertelorism and (in male patients) hypospadias, in addition to a number of midline abnormalities: posterior laryngeal cleft, stridor, swallowing dysfunction, cardiac defects, imperforate anus, and urinary tract and CNS anomalies. Inheritance is autosomal dominant (McKusick number * 145410) with partial male sex limitation in most pedigrees. We report a Dutch family with Opitz BBBG syndrome in which the proband developed late-onset symptoms of a structural laryngeal abnormality.     

A patient with an interstitial duplication of chromosome 5p11-p13.3 further confirming a critical region for 5p duplication syndrome

Partial or complete trisomy 5p has been associated with characteristic facial features, developmental delay, seizures, congenital heart defects, and respiratory compromise. We present a child with developmental delay, seizures, and congenital cardiac anomalies found to have a previously unreported de novo interstitial duplication of chromosome 5p, 46,XX,dup(5) (p11p13.3). The breakpoints of the duplication were further confirmed by fluorescence in situ hybridization analysis using bacterial artificial chromosome probes specific for the affected region. Comparison with previously reported cases of patients with duplications of 5p suggests loci of interest for both congenital heart anomalies and seizures.     

Diagnosis of a terminal deletion of 4p with duplication of Xp22.31 in a patient with findings of Opitz G/BBB syndrome and Wolf-Hirschhorn syndrome

Opitz G/BBB syndrome (OS) is a congenital midline malformation syndrome characterized by hypertelorism, hypospadias, cleft lip/palate, laryngotracheoesophageal abnormalities, imperforate anus, developmental delay and cardiac defects. The X-linked form is caused by mutations in the MID1 gene, while no gene has yet been identified for the autosomal dominant form. Here, we report on a 15-year-old boy who was referred for MID1 mutation analysis with findings typical of OS, including apparent hypertelorism, hypospadias, a history of feeding difficulties, dysphagia secondary to esophageal arteria lusoria, growth retardation and developmental delay. No MID1 mutation was found, but subsequent sub-megabase resolution array CGH unexpectedly documented a 2.34 Mb terminal 4p deletion, suggesting a diagnosis of WHS, and a duplication in Xp22.31. Wolf-Hirschhorn syndrome (WHS) is a contiguous gene deletion syndrome involving terminal chromosome 4p deletions, in particular 4p16.3. WHS is characterized by typical facial appearance ("Greek helmet facies"), mental retardation, congenital hypotonia, and growth retardation. While the severity of developmental delay in this patient supports the diagnosis of WHS rather than OS, this case illustrates the striking similarities of clinical findings in seemingly unrelated syndromes, suggesting common or interacting pathways at the molecular and pathogenetic level. This is the first report of arteria lusoria (esophageal vascular ring) in a patient with WHS.     

一例新发生的5p部分单体合并隐匿18p微小重复

目的 对1例临床表型严重的疑似猫叫综合征患者的核型进行确诊,为评估该家庭的再发风险提供依据.方法 采用高分辨G-显带核型分析患者及其父母,应用猫叫综合征关键区基因位点特异性探针(5p15.2,D5S23/D5S721)、Tel 5p/5q、Tel 18p/18q亚端着丝粒探针和18号染色体涂染探针进行荧光原位杂交(fluorescence in situ hybridization,FISH)检测患者及其父母,SNP-Array对患者全基因组DNA进行扫描分析.结果 高分辨G-显带核型分析发现患者5p末端有微小缺失.应用猫叫综合征关键区基因位点特异性探针荧光原位杂交结果发现患者D5S23/D5S721位点缺失.高密度的SNP-Array芯片检测结果显示该患者5号染色体短臂末端存在15 Mb片段的缺失合并18号染色体短臂末端存在约2 Mb的重复.应用5p亚端着丝粒探针和18p亚端粒探针进行FISH进一步确定了患者携带一条源于5p和18p易位而来衍生的5号染色体.最终确定其染色体核型为46,XY,der(5)t(5;18)(p15.1;p11.31)dn.结论 SNP-Array结合FISH技术确诊了患者为新发生的5p部分缺失合并隐匿的18p部分重复,在其家庭复发风险低.SNP-Array能检出微细的染色体不平衡改变,对于染色体的病因学分析及复发风险评估具有重要价值.     

Direct duplication of 9p22→p24 in a child with duplication 9p syndrome

A de novo direct duplication of 9p22→p24 was shown in a child with a duplication 9p phenotype by GTG banding and fluorescence in situ hybridization (FISH) using a chromosome-9 specific painting probe as well as 6 YAC DNA probes localized to the 9p13–9p23 region. The breakpoints in this patient and previously reported patients suggest that 9p22 may be the critical region for duplication 9p syndrome. Am. J. Med. Genet. 77:268–271, 1998. © 1998 Wiley-Liss, Inc.     

De novo partial 2p duplication with postmortem description

A new syndrome characterized by sensorineural hearing loss (beginning in early infancy), progressive optic nerve atrophy, and dementia (beginning in adult-hood) is described in 3 males in the same family. This is probably an X-linked recessive trait.     

Apparent Fryns syndrome in a boy with a tandem duplication of 1q24-31.2

We report on a newborn boy with manifestations of Fryns syndrome who also had a mosaic tandem duplication of chromosome 1q24-31.2. The child had a diaphragmatic hernia, cleft palate, hypoplastic and absent digits, micrognathia, long philtrum, thin upper lip, and anteverted nose. The baby died at age 5 hours. An autopsy demonstrated absent right middle lobe of the lung, bilateral renal cysts, hypoplastic renal arteries, urethral stricture, hydronephrosis, and aortic coarctation. The brain was abnormal with absent olfactory tracts and cerebral and cerebellar heterotopias. This is the first report of a chromosome anomaly in a child with Fryns phenotype. It suggests that the gene for Fryns syndrome may be located in the region 1q24-31.2.     

De novo partial duplication of chromosome 7p in a male with autistic disorder

We describe a de novo partial duplication of 7p in a 25-year-old male with autistic disorder (AD). High-resolution chromosome analysis revealed an extra segment added to the proximal short arm of chromosome 7. The G-band pattern was consistent with an inverted duplication of 7p11.2-p14.1. Fluorescent in situ hybridization (FISH), using a whole chromosome 7 DNA probe (Cytocell, Inc., UK), confirmed that the extra chromosome material is derived from chromosome 7, indicating that the patient is partially trisomic for a region of the short arm of chromosome 7. Partial duplication of the short arm of chromosome 7 is uncommon with little more than 30 cases in the literature. This is the first report of an individual with a 7p duplication who also has AD.     

16p subtelomeric duplication: a clinically recognizable syndrome

We report on two patients with duplication of the subterminal region of chromosome 16p (dup16p) recognized by fluorescent in situ hybridization (FISH) telomere analysis, presenting with closely overlapping facial features and neurological impairment. Distinct facial anomalies included high forehead, sparse eyebrows, blepharophimosis, short nose, everted upper lip, high-arched palate, wide-spaced teeth, and cupped anteverted ears. Susceptibility to vascular anomalies, in particular pulmonary hypertension and portal cavernoma, was found in one patient. Subtelomeric analysis by FISH demonstrated a de novo duplication of the subtelomeric region of chromosome 16p and a deletion of the subtelomeric region of chromosome 4q in case 1, and duplication of the subtelomeric region of 16p and a deletion of the subtelomeric region of 21q, resulting from malsegregation of a balanced maternal traslocation t(16pter;21qter) in case 2. The extension of duplicated regions measured by array-comparative genome hybridization was about 12 Mb on 16p13.3p13.13 in case 1, and about 8.5 Mb on 16p13.3p13.2 in case 2. In conclusion, we reported a clinically recognizable disorder in two patients with dup16p. Pulmonary hypertension, vascular ring, and manifestations of vascular disruption, as terminal hypoplasia of hands and aplasia cutis, have been previously described in association with dup16p. Thus, susceptibility to pulmonary vascular disease and other vascular anomalies can be a feature of dup16p, suggesting that this subtelomeric region in some respect could be related to vascular anomalies.     

Interstitial tandem duplication of 6p: a case with partial trisomy (6)(p12p21.3)

A de novo interstitial tandem duplication of 6p12p21.3 was observed in a 7-month-old boy with growth retardation, psychomotor delay and craniofacial, brain, limb, and genital anomalies. Fluorescent in situ hybridization using a chromosome 6 paint probe demonstrated that the extra material belonged to chromosome 6. Although it has been suggested that 6p25 is the critical band involved in the expression of the phenotype of 6p duplication, comparison of the clinical findings of this case with those from the literature cases showed strong similarities.     

Apparent Smith–Lemli–Opitz syndrome in a child with a previously undescribed form of mucolipidosis not involving the neurons

A diagnosis of Smith–Lemli–Opitz syndrome was made shortly after birth in a small-fordates infant, on the basis of a characteristic face, penoscrotal hypospadias, bilateral postaxial hexadactyly, and bilateral syndactyly of toes 2–3. The clinical course was marked by failure to thrive, severe delay, refractory myoclonic jerks beginning at age 2 months, and increasing hepatosplenomegaly. He developed corneal clouding and increased gingival hypertrophy and died at age 18 weeks. Autopsy disclosed widespread storage of mucopolysaccharides and lipids within the macrophages and, to a lesser extent, parenchymal cells, of all organ systems. There was extensive demyelination of the cerebral white matter, and dystrophic calcification in the cerebrum, cerebellum, and brainstem. There was no evidence of primary neuronal involvement in the storage. Although the chance concurrence of 2 uncommon diseases is rare, a causal link between the clinical anomalies and the storage disorder cannot be argued convincingly on the basis of one case. Careful pathologic studies of other children who die with clinical signs compatible with Smith–Lemli–Opitz syndrome are indicated.     

Probable Opitz trigonocephaly C syndrome with medulloblastoma

We report on a patient with trigonocephaly, biparietal widening as a result of metopic synostosis, strabismus, upslanted palpebral fissures, apparently low-set ears with abnormal helices, deeply furrowed palate, postaxial polysyndactyly of the feet, ankle flexion deformities, cryptorchidism, loose skin, and severe mental retardation, findings compatible with a diagnosis of the Opitz trigonocephaly C syndrome (OTS). At the age of 12 years this patient presented with symptoms of raised intracranial pressure. A biopsy showed findings diagnostic of a medulloblastoma WHO Grade IV, an unprecedented finding in OTS. The possibility of coincidence should not prevent continued surveillance of OTS patients in the future for the occurrence of malignancy. Am. J. Med. Genet. 69:395–399, 1997. © 1997 Wiley-Liss, Inc.