Studies of malformation syndromes of man VB: The hypertelorism-hypospadias (BBB) syndrome

We describe a boy with the hypertelorism-hypospadias (BBB) syndrome. His mother and his maternal grandmother showed minor manifestations suggestive of the syndrome. The BBB syndrome is a syndrome of multiple congenital anomalies with mental retardation due a segregating mendelian mutation, either X-linked or autosomal. This paper reviews the literature on the subject and emphasizes the problem of identifying females at high risk of transmitting the condition.Supported by Grant 75/0186 from FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo), São Paulo, BrazilSupported by DHEW/PHS Grant GM 20 130 from the National Institute of General Medical Sciences. Paper No. 2055 from the University of Wisconsin Laboratory of Genetics     

Female hypospadias with neurogenic bladder

Female hypospadias is a rare anomaly in which the urethral orifice is located on the anterior vaginal wall close to the introitus. The condition is also associated with a neurogenic voiding disorder that is poorly understood [3]. We report two children aged 3 and 9 years who were managed with clean intermittent catheterization after a Mitrofanoff operation.     

Velofacial hypoplasia (Sedlackova syndrome): a variant of velocardiofacial (Shprintzen) syndrome and part of the phenotypical spectrum of del 22q11.2

In 1955, a pattern of velar hypoplasia causing hypernasal speech and associated facial dysmorphism was observed in 26 children of Czech origin. Further cases with submucous cleft and/or cardiac anomalies were described. In 1978 velocardiofacial syndrome (VCFS) was reported, a condition very similar to velofacial hypoplasia (Sedlackova syndrome) apart from overt clefts instead of velar hypoplasia. In 1990 it was suggested that both syndromes might be variants of the same clinical entity. To test this hypothesis we performed fluorescence in situ hybridisation using the DiGeorge/VCFS region specific probe D22S75 on 20 patients originally classified as Sedlackova syndrome as well as molecular investigations for a subset of these patients. A 22q11.2 deletion was found in 16/20 patients. Thus, our results confirm the aforementioned hypothesis and expand the long list of clinical diagnoses associated with del 22q11.2. CONCLUSION: Velofacial hypoplasia (Sedlackova syndrome) and velocardiofacial (Shprintzen) syndrome have a corresponding phenotype and are both associated with del 22q11.2.     

The Mathieu Righini technique for mid-distal hypospadias repair

In a series of 1,989 operated cases of hypospadias, the technical details, precise indications, and results in 408 consecutive cases of distal and mid-penile hypospadias without chordee using the one-stage Mathieu-Righini procedure are described. This technique employs a meatal flap in which the prepuce is preserved and reconstructed. Twelve fistuals occurred, the majority in the initial phase of the experience, and 2 cases of meatal stenosis were easily managed by dilations. The overall complication rate was 3.4%. This technique provides very good cosmetic and functional results: the penis is normal in appearance as well as function. In the author's opinion, the Mathieu-Righini technique is the procedure of choice for mid-distal hypospadias without chordee repair.     

Disturbances in bile acid metabolism of infants with the Zellweger (cerebro-hepato-renal) syndrome

The bile acid pattern in bile and serum from two infants with the cerebro-hepato-renal syndrome of Zellweger was severely disturbed. An increased concentration particularly of trihydroxycoprostanic acid and also of dihydroxycoprostanic acid could be demonstrated. A generalized mitochondrial defect could explain these increased concentrations. This hypothesis is supported by the abnormal structure of the mitochondria in the liver biopsy of one of our patients. It is possible that the abnormal bile acids contribute to the liver damage of infants with Zellweger syndrome.     

Rubinstein-Taybi syndrome (RTS) with postaxial polydactyly of the foot: 4-year follow-up until improvement of dysbasia

Rubinstein-Taybi syndrome (RTS), also known as 'broad thumbs syndrome' or 'broad thumb-hallux syndrome', is a malformation syndrome characterized by the triad of broad thumbs or first toes, a peculiar facial expression called 'comical face' and mental retardation. Although various malformations are combined with the triad, polydactyly is rare. We treated a male patient with RTS complicated by postaxial polydactyly of the foot. His clinical course was different from typical patients with polydactyly, especially in the aspect of walking development. Osteoplasty-combined surgery, which was ideal for anatomical reconstruction, was performed on the patient at 2 years and 11 months of age. A 4-year follow-up period was required until there was an improvement of dysbasia.     

Bilateral Swyer-James (Macleod's) syndrome

Swyer James syndrome (SJS) is a rare disorder. It is generally discovered on a chest radiograph as increased translucency involving one hemithorax with diminished vascular markings. We present a 5-year-old girl admitted for the treatment of recurrent bronchiolitis. She was diagnosed as having Swyer James syndrome from the results of CT scan and ventilation perfusion scintigraphy, which revealed unsuspected bilateral involvement. This condition should be considered as a differential diagnosis in a patient with Swyer James (Macleod’s) syndrome without an obvious etiology.     

Eosinophilic chromophobe renal cell carcinoma in a child with hypospadias

Chromophobe renal cell carcinoma (CRCC) is a distinct variant of renal carcinoma generally affecting adults. We report a case of an unusual CRCC, arising in a male child affected by hypospadias. This case demonstrates that CRCC can occur in the pediatric patients and can be associated with genital tract anomalies such as Wilms tumor.     

Gonadal function and glycoprotein hormones in the carbohydrate-deficient glycoprotein (CDG) syndrome

Six females and six males with carbohydrate-deficient glycoprotein (CDG) syndrome type I, aged 4 months to 43 years, were examined for gonadal function and electrophoretic isoform patterns of four glycoprotein hormones: FSH, LH, TSH and erythropoietin. The female patients had a hypergonado-trophic hypogonadism from an early age without detectable ovaries in three cases. In the males, testosterone levels tended to be low with normal or slightly raised gonadotrophin values. None of the four glycoprotein hormone showed any signs of carbohydrate deficiency of the same type as in many liver-synthesized circulating glycoproteins. It is concluded that females with CDG syndrome type I have primary ovarian failure, and that the syndrome does not affect the terminal charged carbohydrate portion in gonadotrophins, TSH or erythropoietin. The characteristic carbohydrate deficiency in some circulating glycoproteins is thus not a generalized feature in this disease.     

Fragile X syndrome among children with mental retardation

Prospective screening for fragile X syndrome was carried out among 1,111 patients with mental retardation who attended the Genetic clinic. Using defined clinical criteria, 55 patients were selected for cytogenetic studies to detect folate sensitive fragile sites. Twenty patients were diagnosed to have the fragile X syndrome. The prevalence of fragile X (A) syndrome was 18 per 1,000 patients of both sexes with mental retardation, 2.8% among male patients with mental retardation, and 5.8% among subjects with nonspecific mental retardation.     

Prospective study of children with Guillain-Barre syndrome

Objectives  To see the pattern, and outcome of Guillain Barre syndrome in this country. Methods  All the children under fifteen years with final diagnosis of Guillain-Barre syndrome formed the subjects of the study. All children with acute flaccid paralysis were investigated for the underlying cause. The diagnosis of Gullain-Barre syndrome was made on clinical criteria, cerebrospinal findings and the nerve conduction studies. Intravenous immunoglobulins were given to all and only two children needed plasmapharesis. Result  Fifty-two children were seen and constituted 20% of total acute flaccid paralysis cases. Cranial nerves were involved in fifty percent children. Albuminocytological dissociation in cerebrospinal fluid was seen in 97.5 percent cases. Acute relapse was seen in 11.5%. Seventeen percent required ventilation. The complete recovery was seen in 45 to 282 days (mean 68 days). Three children (5.8%) were left with minimal residual defecit. There was no mortality. Conclusion  The Guillain-Barre syndrome, though is a serious disease, recovery is the rule in children. Very low mortality and morbidity is seen. Immunoglobulins have reduced the length of hospital stay and also reduced the total time for recovery.     

Pituitary function in a patient with septo-optic dysplasia and pituitary dwarfism (Kaplan-Grumbach-Hoyt syndrome)

The case of a seventeen-year-old female patient with septo-optic dysplasia and pituitary dwarfism is presented. Mental retardation and epilepsy, in addition to absence of the septum pellucidum, point to a widespread lesion of the central nervous system. There is unilateral hypoplasia of the optic nerve. She is of small stature. The dynamic pituitary tests point to deficiency of GH, TSH and ACTH, and an adequate reserve of prolactin, gonadotrophins and vasopressin. TSH insufficiency is probably of primary pituitary origin.     

Urethral advancement in hypospadias with a distal division of the corpus spongiosum: Outcome in 158 cases

ObjectiveOutcome of urethral mobilization and advancement (Koff procedure) in hypospadias with a distal division of the corpus spongiosum and redo cases with distal urethral failure.Materials and methodsFrom January 1999 to November 2012, 158 children with a distal hypospadias (115 primary cases and 43 redo cases) underwent surgical repair using the Koff technique with a median age at surgery of 21 months (range, 12–217 months).ResultsMean follow-up was 19 months (median, 14 months). Thirty patients (19%) presented with a complication (13.9% in primary cases and 32.5% in redo surgery) mostly at the beginning of our experience. Meatal stenosis was the most common one (3.5% in primary case, 6% overall). Ventral curvature (>10°), which is considered as a possible long-term iatrogenic complication of the Koff procedure, was not found in patients with fully grown penis except in one redo patient who had, retrospectively, an inadequate indication for this type of repair. Of 158 patients, 33 reached the age of puberty (>14 years old) with a mean follow-up of 34 months, only one presented with a significant ventral curvature.ConclusionUrethral mobilization and advancement is a reasonable alternative for anterior hypospadias and distal fistula repair in selected cases. It has two major advantages compared to other techniques: it avoids any urethroplasty with non-urethral tissue and eliminates dysplastic tissues located beyond the division of the corpus spongiosum, which may not grow at the same pace as the rest of the penis. Significant iatrogenic curvature in fully grown penis is not supported by this series.     

Formative evaluation to improve prevention of sudden infant death syndrome (SIDS): a prospective study

Aim: To evaluate formative evaluation, a pedagogic method that sensitizes mothers to sudden infant death syndrome (SIDS), as a new way to improve prevention of SIDS. Methods: Prospective and randomized study. Mothers in a test group (n = 148) received an educative questionnaire about SIDS during maternity stay. Three months later, we evaluated, by a telephonic interview, their scores of knowledge and observance of the recommendations in comparison with a control group (n = 144). Results: Mothers’ scores at the educative questionnaire was 5.12 (1.52) [mean(standard deviation)]. The scores performed 3 months later were better in test group for knowledge [7.64 (1.56) vs. 7.16 (1.61), p < 0.01] and for observance [8.28 (1.51) vs. 7.62 (1.72), p < 0.001]. Logistic regression analysis confirmed the benefits in test group regarding knowledge of SIDS risk factors [ORa = 1.69 (1.02–2.77), p < 0.05], of the advice to avoid overheating infants [ORa = 2.50 (1.43–4.38), p < 0.01] and of the risks of bed sharing [ORa = 2.7 (1.6–4.5), p < 0.001]. There was a significant association between non‐compliance with the sleeping position recommendation and unemployment (p < 0.01) and absence of postsecondary school education (p < 0.01). Conclusion: Formative evaluation using an educative questionnaire could improve maternal awareness on SIDS risk factors and their compliance with recommendations about SIDS prevention.     

The neonatal pseudo-hydrocephalic progeroid syndrome (Wiedemann-Rautenstrauch)

A boy with the pseudo-hydrocephalic progeroid syndrome (McKusic 26409) [7] is presented and compared to five previously reported children. The boy presented with major skeletal abnormalities, which receded during the first few months of life. Special investigations like studies on collagen, electron microscopy, and growth studies of fibroblasts did not contribute to our knowledge of the pathogenesis of this rare disease.Abbreviations WRS Wiedemann-Rautenstrauch syndrome (pseudohydrocephalic progeroid syndrome) - HGP Hutchinson-Gilford progeria - VLDL very low density lipoproteins - LDL low density lipoproteins - HDL high density lipoproteins     

Congenital central hypoventilation syndrome (Ondine's curse syndrome) in two siblings: Delayed diagnosis and successful noninvasive treatment

Congenital central hypoventilation syndrome (CCHS, Ondine's curse syndrome) is a rare respiratory disorder; less than 100 cases have been reported. Familiality of the disease has been discussed, but only few familial cases have been reported so far. In this report we describe the occurrence of CCHS in two male siblings. Diagnosis was established only at the age of 4 years in the first case, although the patient had disease related symptoms since early infancy. The second patient was one of dizygotic twins, he was diagnosed with CCHS at the age of 8 months. Up to that age only moderate desaturations had been observed. The other twin was unaffected by the disease. Both patients were successfully treated by nocturnal positive-pressure ventilation via a specially adapted face mask. They show satisfactory physical and neurologic development.     

The tay syndrome (congenital ichthyosis with trichothiodystrophy)

We report a 5-year-old boy affected with the Tay syndrome, and give a review of 12 pertinent cases previously reported under various designations. The Tay syndrome is a distinct type of congenital ichthyosis characterized by a peculiar anomaly of hair growth which has been termed trichothiodystrophy. The hair shafts are extremely brittle, and they show alternating light and dark banding when examined microscopically between polarizing filters. Other features of this syndrome are low birth weight, short stature, mental retardation, delayed neuromuscular development and other CNS anomalies, dysplasia of nails, hypoplasia of subcutaneous fatty tissue, prematurely aged facial appearance, hypogonadism, cataracts, osteosclerosis, dysphonia, and increased susceptibility to infections. The syndrome is inherited as an autosomal recessive trait. We delineate the criteria for distinguishing this gene defect from other types of congenital ichthyosis associated with disturbed hair growth, as well as from other types of trichothiodystrophy which are not associated with ichthyosis.