Rafael Fabiano Machado Rosa

Central nervous system abnormalities in patients with oculo-auriculo-vertebral spectrum (Goldenhar syndrome)

OBJECTIVE To describe the central nervous system (CNS) alterations present in a sample of oculo-auriculo-vertebral spectrum (OAVS) patients, trying to correlate them with other clinical features. METHOD Seventeen patients with diagnosis of OAVS were evaluated. All presented radiological evaluation of the CNS, normal GTG-Banding karyotype and clinical features involving at least two from the four following areas: oro-cranio-facial, ocular, auricular and vertebral. RESULTS CNS alterations were verified in eight from seventeen patients (47%). Diffuse cerebral hypoplasia, dilated lateral cerebral ventricles (asymptomatic hydrocephalus), corpus callosum dysgenesis and frontal hypodensities were the most frequent abnormalities. Presence of ophthalmologic abnormalities was the only clinical association observed, being significantly more frequent among patients with cerebral alterations (63% versus 11%). CONCLUSION CNS abnormalities are frequent in patients with OAVS, especially in carriers of ophthalmologic alterations. However, the absence of detectable cerebral abnormalities did not exclude the possibility that these subjects will subsequently present neurological symptoms.

Gestational and family risk factors for carriers of congenital heart defects in southern Brazil.

Background:  Congenital heart disease (CHD) is a serious threat to public health. Despite this, its etiology is poorly understood and few cardiac teratogens have been defined. The aim of the present study was to identify gestational and family risk factors for CHD in a sample of patients from a pediatric hospital in southern Brazil.

Wilms tumor: experience of a hospital in southern Brazil.

Wilms tumor (WT) is the most common renal malignancy of childhood. The aim of this study was to verify the epidemiological profile and prognosis of a sample of patients from Brazil and compare them to similar data from other Latin American studies.

Trisomy 12p syndrome secondary to a balanced familial translocation

Trisomy of the short arm of the chromosome 12 (12p) is a rare chromosomal abnormality, whose natural history and life expectancy are still not largely known. Its first description was made by Uchida and Lin (1973), the estimate incidence being 1 for each 50 000 births. Trisomy 12p may occur both in the complete form (involving the whole short arm of the chromosome 12) and in the incomplete form (only part of this short arm), as a pure (single) lineage or in mosaic (involving more than one lineage of cells). However, the complete and pure form is considered very rare. It has been described both as a result of new mutations and, mainly, malsegregation of familial translocations. Here we present a new report on the trisomy 12p syndrome, in its complete and pure form, resulting from malsegregation of a balanced translocation of paternal origin, with additional clinical findings not previously described in the medical literature.

Blepharophimosis-ptosis-epicanthus inversus syndrome.

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Omphalocele‐exstrophy‐imperforate anus‐spinal defects (OEIS) complex in a child with nail‐patella syndrome

We report here the rare case of a 3-day-old girl with nail-patella syndrome presenting concomitantly with omphaloceleexstrophy-imperforate anus-spinal defects (OEIS) complex and a history of exposure to cocaine during the first five months of pregnancy. The mother did not specify the frequency or amount of the drug. At physical examination, the infant presented down-slanting palpebral fissures; low-set and posterior rotated ears with an overfolding of the helices; left hand with an ulnar deviation and absence of palmar creases, clinodactyly of the fifth finger and hypoplastic thumb with proximal implantation; right hand with single palmar crease; lack of dorsal and distal creases of some fingers on both hands; hypoplastic nails on feet and hands; omphalocele; cloacal exstrophy with undefined genitalia, imperforate anus; loose coxofemoral joints and bilateral clubfoot. Elbow movements were apparently normal, being that there was no evidence of cubital pterygium. Knees presented hyperextension, being that the patellas seemed of reduced size or even absent, altering its usual form (Fig. 1). Radiographic evaluation at 4 months of age demonstrated the presence of butterfly thoracic vertebrae, 11 pairs of ribs, pubic symphysis diastasis, sacral hypoplasia and bilateral hip luxation. The infant’s high-resolution karyotype by GTG-Banding was normal (46XX). In the mother’s clinical evaluation a limitation in the extension of both elbows was observed, as well as dysplastic nails. Similar findings were also present in two uncles and the grandfather on the mother’s side. The radiographic evaluation of the mother evidenced bilateral luxation on the radius head and hypoplasia of the patellas. Ungueal hypoplasia, lack of dorsal and distal creases in some fingers, hyperextension of the knees with patellas apparently absent or of reduced size in our patient and a family history of similar findings led to the diagnosis of nail-patella syndrome, a rare and pleiotropic autosomal-dominant disease. Besides the findings previously described, the presence in our patient of omphalocele, cloacal exstrophy, imperforate anus and thoracic vertebrae alteration associated with hypoplasia of the sacrum have led to the concomitant diagnosis of OEIS complex/cloacal exstrophy. In our literature review, we did not find any report of an association between nail-patella syndrome and this complex. However we did come across a report of a patient with OEIS complex presenting as a 9q34.1-qter deletion secondary to a de novo translocation between chromosome 9q and Yq, and the gene for nail-patella syndrome (LMX1B) is localized within this region. Cocaine, on the other hand, is an illicit drug that may lead to tachycardia, arrhythmia, high blood pressure and reduction of uterus blood flow during pregnancy, alterations that can cause fetal damage, secondary to hypoxia. Urinary tract abnormalities have been associated with maternal exposure to cocaine in some studies. Interestingly, despite the fact that we could not find any report of a specific association between the OEIS complex and use of cocaine during pregnancy in the literature, in the study by Chávez et al., one of the patients had cloacal persistency. The cause of OEIS complex is possibly heterogeneous, including genetic as well as environmental causes. Among the latter would be agents that would lead to a uterine-placental insufficiency in a very early period of the embryonary development, still during blastogenesis. Keppler-Noreuil described cases of OEIS where the mothers had made use of recreational drugs during pregnancy, but did not make any mention of cocaine. However, it is interesting to note that there are reports of associations of OEIS with the use of certain medicines, such as phenylhydantoin and methamphetamine, which present cardiovascular effects. Besides that, although cocaine may cause hypoxia to the embryo through the constriction of the uterine artery, it has been demonstrated that it blocks the human etherà-go-go-related gene potassium channel in humans, leading to fetal hypoxia secondary to arrhythmia, in a similar way to phenylhydantoin. Against this entire panorama and the history of fetal exposure to cocaine during the first five months of pregnancy, we cannot exclude the possibility that the OEIS complex observed in our patient has happened due to fetal exposure to this drug. On the other hand, there is still a chance that the association between the findings in our patient may have been merely occasional. Correspondence: Giorgio Adriano Paskulin, MD, PhD, Genética Clínica – UFCSPA/CHSCPA, Rua Sarmento Leite, 245 / 403, CEP: 90050-170, Porto Alegre, RS, Brazil. Email: paskulin@ufcspa.edu.br Received 13 January 2010; revised 15 April 2010; accepted 31 May 2010. Pediatrics International (2010) 52, 847–848 doi: 10.1111/j.1442-200X.2010.03216.x