Sefik Guran

Persistent mullerian duct syndrome with transverse testicular ectopia

A 15-month-old boy was discovered to have internal female genitalia during an operation for bilateral inguinal hernia. The biopsies showed normal testicular tissue and the karyotyping result was 46XY, so the diagnosis of persistent mullerian duct syndrome (PMDS) was made. At the second operation, the uterine fundus and fallopian tubes were excised. Then, he underwent bilateral orchiopexy. We discuss a rare presentation of this disorder, its management, and genetic implications together with a review of the literature.

Gorlin-Chaudhry-Moss syndrome revisited: expanding the phenotype.

Gorlin–Chaudhry–Moss syndrome (OMIM 233500) is a rare congenital malformation syndrome with the cardinal manifestations of craniofacial dysostosis, hypertrichosis, underdeveloped genitalia, ocular, and dental anomalies. Since 1960, only six affected individuals have been reported. We report a 4‐year and 6‐month‐old female patient with this phenotype and review the clinical presentation of all patients known so far. Previously unreported malformations of the extremities, larynx, and nose are also described, expanding the phenotype of this rare syndrome. Array‐CGH analysis did not show pathological deletions or duplications.

A new syndrome associated with absence of lower lid lacrimal punctum, ptosis, elevation deficiency of both eyes and mild facial dysmorphism.

A considerable volume of literature has been published on the association of lacrimal outflow dysgenesis with developmental anomalies or systemic syndromes. We report three affected individuals in a consanguineous family those are associated with bilateral ptosis, upper ocular movement limitation, and absence of the lacrimal punctum. T our knowledge, this is the first article reporting the association of bilateral ptosis, facial dysmorphism, upper ocular movement limitation, and absence of the lacrimal punctum in a hereditary form. As a sole example, these findings may be accepted as a new syndrome with autosomal recessive pattern because of consanguinity.

A papillary thyroid carcinoma case associated with hereditary colon carcinoma due to familial adenomatous polyposis with no hereditary mutation finding

Dear Editor: Familial adenomatous polyposis (FAP) is characterized by multiple intestinal adenomatous polyps, congenital hypertrophic retinal pigment epithelial (CHRPE) lesions, epidermoid cysts, and osteomas on the mandible. If left untreated, one or more of these colorectal polyps will progress to colorectal cancer typically by the age of 40 years with consequent need for prophylactic surgery. Cases with accompanying thyroid carcinoma had been reported with only 1–2% of patients with a history of FAP and are found mostly in young women aged 30 or below at the time of diagnosis. We present a case with hereditary colorectal carcinoma due to a history of FAP and papillary thyroid carcinoma with no hereditary mutation observed in the analyses of APC, TP53, BRCA1, and BRCA2 genes. A 34-year-old woman was admitted complaining of dyspepsia and constipation. Her physical examination revealed tenderness and a palpable mass in the left pelvic area. In her past medical history, she was diagnosed with papillary thyroid carcinoma, underwent a total thyroidectomy with central compartment of neck node dissection in 1996, and was still in remission. In pelvic ultrasound examination a huge tumor (15.3×10.7 cm) was reported; pelvic magnetic resonance imaging also revealed a large tumor (17.0×13.0×9.0 cm) in the left parametrium. Results for tumor markers (CEA, CA 19-9, CA 15-3, and CA 125) were unremarkable. She was subjected to pelvic exploration with a diagnosis of an ovarian tumor. Exploration showed an infiltrating tumor in the left ovary originated from the rectosigmoid junction. Further exploration showed that there was a synchronous tumoral mass in the left colon and polyposis coli throughout the entire colon. Subtotal colectomy with Hartman pouch was performed, and the pathology was reported as polyposis coli with undifferentiated adenocarcinoma of the colon in two localizations, which infiltrated to the ovary and tuba uterine. After the surgical examination, adjuvant chemotherapy was planned. In her detailed pedigree analyses, a history of FAP was observed in her father and one of her uncles. The patient and her brother had no routine colonoscopy analyses. Different molecular analyses were performed on the candidate genes to find the hereditary gene mutations in this family. The DNA was isolated from peripheral blood of the patient by using standard protocol; mutation analyses of APC gene (exons 1 to 15) were amplified. Exons 5–9 of the p53 gene were amplified using primers designated from the published sequence. PCR was performed according to standard methods. The common mutations of BRCA1 and BRCA2 genes (2312del5, 2800delAA, 3166ins5, G. Yagci (*) Department of Surgery, Gulhane Military Medical Academy, Etlik, 06018 Ankara, Turkey e-mail: gyagci@gata.edu.tr Tel.: +90-312-3045113 Fax: +90-312-3045002

Rare chromosomal complement of trisomy 21 in a boy conceived only by IVF.

In the article ‘Rare chromosomal complement of trisomy 21 in a boy conceived by IVF and cryopreservation’ presented in Reproductive BioMedicine Online (Quiroga et al., 2009) a case of mosaic Down syndrome with an unusual karyotype was reported. The chromosomal complement consisted of two different cell lines, one predominantly trisomic with a derivative chromosome due to a Robertsonian translocation (21;21) and another carrying a ring chromosome 21. The assisted reproductive techniques and cryopreservation were held responsible in this rare type of mosaic Down syndrome case. This letter presents a similar case with three different cell lines including predominantly a ring 21 chromosome, a Robertsonian translocation (21;21) and a monosomy 21 (Figure 1). The karyotype was 46,XY r(21) [87], 45,XY, 21 [21], 46,XY, t(21;21)(q10;q10) [6] (Figure 1). This one-month old case was born to a non-consanguineous family as the first child. His mother was 29 years old and his father was

NONFUNCTIONING ADRENOCORTICAL CARCINOMA IN A CHILD

Pediatric nonfunctioning adrenocortical carcinoma is a very rare tumor. A 4-year-old girl was admitted complaining of abdominal pain. Physical examination revealed an abdominal mass. There were no clinical or laboratory signs of hormonal abnormality. Abdominal ultrasonography revealed a polylobular mass. Intravenous pyelography showed marked compression of the kidney by a tumor. The tumor was excised together with the right kidney. The histopathological diagnosis was adrenocortical carcinoma. Although there is a greater incidence of germ line p53 mutations with adrenocortical carcinoma, the tumor suppressor gene p53 was not mutated in our case. The girl died 2 months after surgery from complications of chemotherapy.

The progeny of homozygous identical reciprocal translocation carrier mother.

The prevalence of reciprocal translocations among fetuses and newborn infants is estimated at 2–5/1,000. Approximately half of the reciprocal translocation carrier cases inherit these translocations from their parents. The occurrence of a marriage between two balanced reciprocal translocation carriers among all marriages was reported as 1/150,000 [Zaki et al., 2007]. As known, consanguinity between the parents is the most likely cause for the occurrence of identical balanced reciprocal translocation in each parent [Cook et al., 1998; Kupchik et al., 2005; Omrani and Gargari, 2007; Zaki et al., 2007]. The probability of balanced translocation carrier gamete is 1/6 for each parent by 2:2 segregation. Thus, the theoretical risk of having homozygous translocation carrier baby is 1/ 36, if both of the consanguineous couples are carriers for the identical translocation [Cook et al., 1998]. Up to now, very few studies had been reported on balanced reciprocal translocation carriers in homozygous state [Martinet et al., 2006; Zaki et al., 2007]. In this report, we present a healthy mother (the proband; II-3) with homozygous translocation and her progeny (III-3) with heterozygous translocation (Fig. 1A). The proband was referred to our department for recurrent fetal losses. At the time of admission, the proband (II-3) was pregnant. The cytogenetic evaluation of the proband (II-3) showed the homozygous carrier state. To determine the origin of homozygous translocation we performed the parental karyotype analyses. The father (I-3) and the mother (I-4) of the proband (first cousins) had the same translocation each in heterozygous state (Fig. 1A). Finally, the index case (II-3) had ‘‘46,XX,t(5;16)(q22;q24)mat,t(5;16)(q22;q24)pat’’ karyotype, whereas her unconsanguineous healthy husband (II-2) had 46,XY normal constitutional karyotype (Fig. 1B). In the obstetric history of the proband (II-3), the termination of first pregnancy at 6th week of gestation due to absence of fetal heartbeat was noted (III-1). The second pregnancy was complicated by intrauterine death at 28th week of gestation; the autopsy did not reveal any pathological findings (III-2). These kinds of losses are commonly observed in families due to mispairing of homologous chromosomes during gametogenesis if one of the parents has a heterozygous type reciprocal translocation [Zaki et al., 2007]. But theoretically, we do not expect to see mispairing of homologous chromosomes during gametogenesis in a homozygous translocation carrier individual. The change in imprinting pattern due to the translocation may be another probable cause of recurrent fetal loses in our family [Paoloni-Giacobino, 2007]. In the obstetric history of the proband (II-3), an operation for septate uterus was noticed. Septate uterus may be accepted as one of the probable reasons for recurrent fetal loses [Saravelos et al., 2008]. After the operation the uncomplicated pregnancy occurred. The third pregnancy of the proband (II-3) has been followed up to 36th week of gestation. Antenatal ultrasonography showed normal results for the balanced reciprocal translocation carrier fetus (III-3). The fetal karyotype (III-3) performed on amniotic cell culture at the 18th week of gestation revealed the heterozygous carrier state for balanced reciprocal translocation. The heterozygous translocation carrier fetus (III-3) was delivered at the 40th week of gestation, and the neonate was male and according to his physical examination, he was normal (Fig. 1A and 1B). The occurrence of a marriage between two balanced reciprocal translocation carriers estimated as 1/150,000 [Zaki et al., 2007]. As expected, consanguineous parents with the identical balanced reciprocal translocations may have chromosomally unbalanced gametes, and healthy balanced gametes [Kupchik et al., 2005]. In this family, the proband (II-3) had homozygous state balanced reciprocal translocation and her husband (II-2) had normal karyotype results. The chromosomes included in translocation in our family were derived from heterozygous carrier father (I-3) and mother (I-4) of the proband (II-3). The homozygous state translo-