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Re: Small Lesion or Chorioangioma?From: James S Smeltzer MD (gaperina@mindspring.com)Wed Sep 8 22:46:02 1999
Dear EJ, You need to go over these with a geneticist to answer these good questions. Ultrasound can identify taht the fetusd is having trouble with the placenta or with heart failure. At least in theory, the abnormal flow in the arteries feeding and pulsatile flow in veins draining these may be detectable as well. The most common form of this is chorangioma or hemangioma of the palcenta and possibly other organs. These get better without too much problem if the baby does not have heart failure or and lives long enough. There are two dominant conditions (about 50% chance that the infant will inherit the gene, most affected) that come to mind as possibilities: First, Hemangioma-thrombocytopenia syndrome Description: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?141000.cs 141000 HEMANGIOMA-THROMBOCYTOPENIA SYNDROME CLINICAL SYNOPSIS Skin : Giant hemangiomas Heme : Thrombocytopenia Microangiopathic hemolytic anemia Cardiac : Hyperkalemic ventricular arrhythmia Lab : Red cell changes compatible with trauma Hyperkalemia Inheritance : Autosomal dominant Second, especially with the large head: http://www3.ncbi.nlm.nih.gov/htbin-post/Omim/dispmim?153480 #153480 MACROCEPHALY, MULTIPLE LIPOMAS, AND HEMANGIOMATA Alternative titles; symbols BANNAYAN-ZONANA SYNDROME; BZS MACROCEPHALY, PSEUDOPAPILLEDEMA, AND MULTIPLE HEMANGIOMATA BANNAYAN-RILEY-RUVALCABA SYNDROME, INCLUDED; BRRS, INCLUDED BRR SYNDROME, INCLUDED RILEY-SMITH SYNDROME, INCLUDED RUVALCABA-MYHRE-SMITH SYNDROME, INCLUDED; RMSS, INCLUDED Gene Map Locus: 10q23.3 TEXT A number sign (#) is used with this entry because of evidence that this disorder results from mutations in the PTEN gene (601728). The genetic etiology may be heterogeneous since Carethers et al. (1998) could find no PTEN germline mutations in 3 sporadic cases of this disorder. Bannayan (1971) first described this disorder in a single child observed at autopsy at the Johns Hopkins Hospital. Zonana et al. (1975, 1976) described the disorder in a father and 2 sons. One son had overgrowth of the right index finger and involvement of the small bowel mesentery by hamartoma with angiomatous, lipomatous, and lymphangiomatous components. Miles et al. (1981) documented the syndrome in 11 persons in 4 additional families. Features included high palate, scaphocephaly, lipomas of the anterior abdominal wall, thigh, perineum, scapula area, etc., hemangiomas of the anterior abdominal wall, wrist, knee, and foot, bleeding from intracranial hemangioma, and arteriovenous malformation leading to leg amputation. Computerized axial tomography showed no enlargement of the cerebral ventricles. The lipomas spontaneously regress with age. The affected persons show high birthweight and length, but growth levels off at age 6 or 7 years. Bone age is normal. Motor development is delayed and incoordination is a lifelong feature. Speech development is delayed and intelligence is usually mildly retarded. Seizures result from intracranial hemorrhage. Drooling is a problem in children. Some children have pectus excavatum. No pseudopapilledema is observed in this disorder. The disorder appears to be an autosomal dominant but about 80% of affected persons have been male. In 1 instance the disorder was transmitted by a man with a head of normal size. Higginbottom and Schultz (1982) described the syndrome in 3 generations of an American black kindred. They concluded that affected persons may have an increased risk of intracranial tumors: a woman in their family had meningothelial meningioma removed at age 28. Riley and Smith (1960) described mother and 2 of 7 children who had macrocephaly, pseudopapilledema, and multiple hemangiomata. Two other sibs had macrocephaly and pseudopapilledema. Intellect and vision were unimpaired. Ruvalcaba et al. (1980) described as instances of the Sotos syndrome (117550) 2 unrelated patients with macrocephaly, intestinal polyposis, and pigmented macules of the penis. Smith (1982) subsequently suggested that these patients had a different disorder. DiLiberti et al. (1983) described a patient with RMSS whose mother was probably affected. The proband was a 7.5-year-old boy with macrocephaly, hamartomatous intestinal polyps, and cafe-au-lait spots on the penis. The mother had macrocephaly, a facial appearance similar to the son's, and a hamartomatous intestinal polyp. DiLiberti et al. (1983) added prominent Schwalbe lines (a frequent normal finding but a consistent feature of 'anterior chamber cleavage syndromes'), prominent corneal nerves, and lipid storage myopathy as features of the disorder. On the basis of 4 patients, DiLiberti et al. (1984) extended the description of the lipid storage myopathy associated with this disorder. The patients had delayed psychomotor development and/or hypotonia in childhood. Electromyography in 3 patients showed evidence of a myopathic process. Muscle biopsy in all 4 showed a lipid storage myopathy with increased numbers of neutral lipid droplets--predominantly in type 1 fibers. Type 2 fibers were consistently smaller than expected. Dvir et al. (1988) described a patient with macrocephaly, pseudopapilledema, enlarged penis, lipoangiomatosis, and spotted pigmentation of the glans penis. The patient's father and a brother had macrocephaly; the father had enlarged penis. The authors suggested that the Riley-Smith syndrome and the Bannayan-Zonana syndrome (BZS) are the same as the disorder first reported by Riley and Smith (1960). Dvir et al. (1988) proposed to unify the 3 conditions in 1 hereditary syndrome and name it macrocephaly-hamartomas-papilledema. Gorlin (1988) also suggested that RMSS is the same as the Bannayan-Zonana syndrome. He referred to the case of an 8-year-old male who had 50 or more hamartomas of the bowel through which he lost serum protein. The diagnosis of BZS had been made, but Gorlin found that the patient had speckled penis. In a 38-year-old man (R.D.T., JHH 2358085) with macrocephaly, multiple lipomas, and vascular anomalies, Pyeritz (1988) observed 'unstable angina,' dilated aortic root, and ascending aorta. Halal and Silver (1989) described an 8.5-year-old boy with slowly progressive macrocephaly, psychomotor retardation, multiple subcutaneous angiolipomas, hypertelorism, exotropia, prolonged drooling to age 5 years, cutis marmorata, telangiectases over the shoulders, atrial septal defect repaired at age 4 years, broad thumbs and great toes, and muscle wasting. The angiolipomas were bluish subcutaneous nodules scattered all over his body. The parents were second cousins. The father was thought to have minor manifestations of the disorder, i.e., mild hypertelorism and broad thumbs and great toes, as well as mild cutis marmorata over the inner aspect of the forearms and a cluster of telangiectases and dilated vessels on the anterior aspect of both legs. Halal and Silver (1989) concluded that the proband and his father may have had the BZ syndrome (with previously undescribed additional anomalies) overlapping with the syndrome of cutis marmorata telangiectatica congenita (CMTC; 219250); or, alternatively, that the disorder in the father and son represents a new syndrome of macrocephaly and hamartomas with overlapping manifestations with the BZ and CMTC syndromes. Moretti-Ferreira et al. (1989) commented on the variability of severity, which may represent different allelic mutations or genetic heterogeneity. In the sporadic cases of Bannayan (1971) and of Okumura et al. (1986), death occurred as a result of severe visceral lipomatosis at ages 3.5 years and 5.75 years, respectively. Cohen (1990) suggested the designation of Bannayan-Riley-Ruvalcaba syndrome (BRRS). DiLiberti (1990) questioned the evidence that these syndromes are the same. In an 11-year-old male with features of the Bannayan-Zonana syndrome, Israel et al. (1991) found a 19;Y translocation in circulating lymphocytes: 46X,t(Y;19)(q11;q13). They raised the possibility that a small deletion or position effect of chromosome 19q is responsible for this syndrome. DiLiberti (1992) extended the boundaries of this entry further to include benign familial macrocephaly (153470, 248000). He examined the muscle biopsy results from 14 children with macrocephaly and hypotonia/weakness and correlated them with clinical findings. Of the 14, 13 had evidence of lipid storage myopathy, either generalized or focal. All 13 had examinations consistent with either benign familial macrocephaly, Ruvalcaba-Myhre-Smith syndrome, or Bannayan-Zonana syndrome. DiLiberti (1992) suggested that all 3 of these disorders may represent phenotypic variability resulting from mutation at a single genetic locus. Gorlin et al. (1992) reported a kindred with 12 affected members. They expanded the phenotypic spectrum to include Hashimoto thyroiditis, which occurred in 7 of the patients. Fryburg et al. (1994) suggested that a defect in long-chain fatty acid oxidation resulting from deficiency of long-chain-L-3-hydroxyacyl-CoA dehydrogenase (LCHAD; 143450) may be responsible for the lipid myopathy in the Bannayan-Riley-Ruvalcaba syndrome. Their patient had macrocephaly with prominent frontal bossing and low-set ears, hypertelorism, and hemangiomas. Zigman et al. (1997) localized the gene for the Bannayan-Riley-Ruvalcaba syndrome to 10q23 by study of 2 patients with intestinal juvenile polyposis and karyotypic abnormalities involving 10q. Patient 1 was a boy who displayed cognitive and developmental delay, macrocephaly, subcutaneous hamartoma, and hypotonia, in addition to multiple intestinal juvenile polyps. He ultimately underwent a total abdominal colectomy for refractory anemia and failure to thrive. Patient 2 was a girl who had features consistent with Bannayan-Riley-Ruvalcaba syndrome, including hypotonia, cognitive and developmental delay, and multiple intestinal juvenile polyps. This patient also had additional features not typical of BRRS, including atrial and ventricular septal defects, dysplastic pulmonic valve, left superior vena cava draining into a dilated coronary sinus, and bilateral clubfoot. (Three other unrelated patients with the diagnosis of BRRS but without karyotypic abnormalities were also studied; 2 of the 3 patients had pigmentary changes of the penis.) Patient 1 had an unbalanced translocation between chromosomes 10 and 9; patient 2 has an interstitial deletion of 10q23.1-q24.2. In each case, DNA markers allowed localization of the defect to 10q23. Arch et al. (1997) described an 18-month-old patient previously thought to have the BRR syndrome. They found an interstitial deletion of 10q23.2-q24.1. This is the same region as that to which Cowden disease (CD; 158350) maps, as well as the PTEN gene (601728), which is the site of causative mutations in Cowden disease. Cowden disease has been described mainly in adults. Because of the considerable phenotypic overlap between the BRR syndrome and Cowden disease and because of a demonstration in their patient that the PTEN gene was deleted on chromosome 10, Arch et al. (1997) suggested that these are allelic disorders. The 18-month-old patient had macrocephaly (head circumference more than 4 S.D. above mean for age), facial dysmorphism (prominent forehead and hypertelorism), a lipoma on the right abdomen and on the right thumb, 2 small hemangiomas on the back and shoulder, and 2 skin tags at the base of the spine and in the groin area. Psychomotor development was delayed. Ophthalmologic examination showed pseudopapilledema bilaterally. Neither parent had any features of either Cowden disease or BRR syndrome. Hematochezia prompted upper and lower gastrointestinal endoscopy, which showed multiple sessile polyps throughout the duodenum and large intestine. Histology showed that these were hamartomatous. Marsh et al. (1997) demonstrated germline mutations in the PTEN gene in patients with Bannayan-Zonana syndrome. Thus, Cowden disease and BZS are allelic disorders. One of the mutations that Marsh et al. (1997) found associated with BZS, R233X (601728.0002), had previously been reported in association with Cowden disease. The identical mutation occurred in 2 unrelated families with 2 distinct syndromes on 2 different 10q22-q23 haplotypes, arguing against a common ancestor or a founder effect. Longy et al. (1998) identified 4 new mutations in the PTEN gene in 6 patients from 4 unrelated families with Bannayan-Riley-Ruvalcaba syndrome. In 1 family, 1 individual had features more suggestive of Cowden disease, whereas the overall family phenotype was that of Bannayan-Riley-Ruvalcaba syndrome. Celebi et al. (1999) reported a further family with a single PTEN mutation (601728.0021) in which 2 female members had phenotypic findings of Cowden syndrome and 2 males had phenotypic findings of BZS. Carethers et al. (1998) failed to find PTEN germline mutations in 3 sporadic cases of Bannayan-Riley-Ruvalcaba syndrome. One patient, a male, presented with macrocephaly, hypotonia, cognitive and developmental delays, cutaneous lipomas, and a 2-cm intestinal metaplastic polyp located in the ascending colon. The second patient, also a male, presented with macrocephaly, multiple intestinal juvenile polyps, pigmentation of the genitalia, cutaneous and visceral lipomas, cutaneous hemangiomas, and hyporeflexia. Patient 3, another male, presented with macrocephaly, multiple rectal juvenile polyps, pigmentary spotting of the penis, cutaneous lipomas, and cognitive and developmental delay. DiLiberti (1998) proposed a new nomenclature reflecting the unification of multiple syndromes that are now known to be caused by mutations in the PTEN gene. He proposed that it be called the PTEN MATCHS syndrome; MATCHS was derived from macrocephaly, autosomal dominant, thyroid disease, cancer, hamartomata, and skin abnormalities. Marsh et al. (1999) screened for PTEN mutations in constitutive DNA samples from 43 Bannayan-Riley-Ruvalcaba syndrome individuals comprising 16 sporadic and 27 familial cases, 11 of which were families with both Cowden disease and BRRS. Mutations were identified in 26 of 43 (60%) BRRS cases. Genotype-phenotype analyses within the BRRS group suggested a number of correlations, including the association of PTEN mutations and cancer or breast fibroadenoma in any given CD, BRRS, or BRRS/CD overlap family (P = 0.014), and, in particular, truncating mutations were associated with the presence of cancer and breast fibroadenoma in a given family (P = 0.024). Additionally, the presence of lipomas was correlated with the presence of PTEN mutation in BRRS patients (P = 0.028). In contrast to the report of Carethers et al. (1998), in which no PTEN mutations or deletions were found in sporadic cases of BRRS, Marsh et al. (1999) found that identification of germline PTEN mutations was equally likely in sporadic and familial BRRS (P = 0.113). Comparisons between BRRS and a previously studied group of 37 CD families suggested an increased likelihood of identifying a germline PTEN mutation in families with either CD alone or both CD and BRRS when compared with BRR alone (P 0.002). Among CD, BRRS and BRRS/CD overlap families that were PTEN mutation positive, the mutation spectra appeared similar. Thus, PTEN mutation-positive CD and BRRS may be different presentations of a single syndrome and, hence, both should receive equal ttention with respect to cancer surveillance. ... I therefore recommend that you gather up the babies & their medical information & see the geneticist for an answer to these questions. It is an areal of current research and better genetic prenatal diagnosis tools may be possible some day - if not now. Hope this helps, Jim Smeltzer MD
At 05:13 PM 9/6/1999 -0500, you wrote:
>I had placenta chorioangiomas with both of my children. The pathologist
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