Ambiguous genitalia in the Proteus syndrome.

An 11-year-old girl was followed up since birth because of hemihypertrophy of the left leg and thigh, multiple pigmented nevi and subcutaneous tumors typical of the Proteus syndrome. Because of clitoromegaly and scrotal-like hypertrophy of the labia majora, she had an endocrine evaluation the results of which were normal. The findings are thought to represent local genital hypertrophy. Ambiguous genitalia have to be added to the phenotype of the Proteus syndrome.

Trigonocephaly: a new familial syndrome.

Trigonocephaly was found in six relatives through three generations of one family. The propositus was ascertained at birth because of omphalocele. In addition to trigonocephaly, he had minor ear, vertebral, and genital abnormalities. His father had mild microcephaly, and both had minor eye abnormalities. None of the other four affected individuals had any other malformations. In this family, trigonocephaly is an autosomal dominant trait. The ratio of affected males to affected females was 5 to 1, and although the paucity of affected females is not statistically significant, we speculate that it may reflect variable expressivity or sex limitation of the trait. We conclude that the condition in this family represents a unique syndrome in which trigonocephaly is not associated with functional brain abnormalities and where craniosynostosis is limited to the metopic region.

Váradi syndrome (OFD VI) or Opitz trigonocephaly syndrome: overlapping manifestations in two cousins.

We report on 2 cousins, offspring of consanguineous matings, with multiple congenital anomalies. Square face, frontal bossing with metopic ridge, small anteverted nose, flat nasal bridge, slanted palpebral fissures, and epicanthal folds contributed to an unusual appearance. Multiple bucco-alveolar frenula and notched inferior alveolar ridges were present at birth and one had a notched uvula and submucous cleft of the hard palate. Both had congenital heart anomalies, micropenis, and cryptorchidism. Persistence of Müllerian structures was documented at necropsy in one patient. The surviving patient was mentally retarded and had unilateral central hexadactyly and partial agenesis of the corpus callosum. Bulimia and episodic hyperthermia were attributed to hypothalamic dysfunction. Results of unstimulated endocrine studies and gonadotropin releasing hormone (GnRH), and human chorionic gonadotropin (HCG) stimulation tests were normal. The manifestations of the 2 patients overlap those reported in the OFD VI and Opitz trigonocephaly syndromes.

Familial simple hypohidrosis with abnormal palmar dermal ridges.

A brother and sister born to nonconsanguineous, Iranian Jewish parents were found to have simple hypohidrosis. Pilocarpine produced only little sweating, and external heat and physical effort were associated with elevation of body temperature. Abnormal palmar dermal ridges were considered to be associated with paucity of sweat pores and glands. Biopsy supported this view since only one normal sweat gland and duct was found in a 5 mm punch.

Familial lipoid adrenal hyperplasia: genetic marker data and an approach to prenatal diagnosis.

Some of the anatomic endocrine, and genetic aspects of lipoid adrenal hyperplasia were studied in an inbred Israeli-Arab family with two affected sibs. One sib, a genetic female, presented with acute Addisonian crisis. Endocrine studies documented elevated ACTH levels and no detectable steroids of gonadal or adrenal origin. The other patient, a male pseudo-hermaphrodite, was found at autopsy to have typical lipoid adrenal hyperplasia and ectopic adrenal tissue adjacent to an intra-abdominal testicle. Complete vagina, uterus, and fallopian tubes were present in addition to the Wolffian structures. This unique observation supports the view that steroids may be necessary for Müllerian inhibitory factor to induce regression of Müllerian structures. The segregation of 27 autosomal markers was studied in one affected and five unaffected sibs. Genetic linkage to HLA, MNS, and GPT is unlikely. In addition, the affected sib is heterozygote for a haplotype of chromosome 1 which includes the Rh, Fy, PGM-1 systems. Determination of fetal gender by the combined use of ultrasonography and amniocentesis is suggested for prenatal diagnosis and improved risk counselling.

MODED: microcephaly-oculo-digito-esophageal-duodenal syndrome.

We report on 4 families with microcephaly, type A brachydactyly, variable learning disabilities, short stature, duodenal atresia, patent ductus arteriosus (PDA), hallux valgus, restricted elbow and finger movements, and amesophalangy and syndactyly of toes. Three previous families manifested all signs of the syndrome, and in another four reports the phenotype was incomplete. These cases are reviewed. Penetrance of digital and toe anomalies is almost complete and microcephaly is present in 78% of known cases. Short stature was present in 70% of our cases, but this is probably an overestimation. Esophageal and duodenal atresias were present in 25% of known cases. Correction for ascertainment bias gave a lower estimate of 16.6%. Learning disabilities were present in 31% of all patients. Longitudinal follow-up suggested that hypoplasia or absence of the diaphyseal ossification centers is the primary cause of the phalangeal changes. Observations in a 9-year-old girl, followed since age 3.3, suggest that the eventual absence of the middle phalanges of the toes may be caused by fusion.

Syndrome of alopecia totalis and 17b-hydroxysteroid dehydrogenase deficiency.

A distinct and previously undescribed syndrome of alopecia totalis, ichthyosis, and male pseudohermaphroditism due to steroid 17b-hydroxysteroid dehydrogenase deficiency was observed in an Israeli-Arab newborn infant.

Phenotypic expression of tissue mosaicism in a 45,X/46,X,dicY(q11.2) female.

We describe a girl who presented at the age of 11 years with short stature. She had female external genitalia and some clinical features of Turner syndrome. At laparotomy a uterus and Fallopian tubes and small gonad-like tissue masses in the region of the Fallopian fimbria were found. The tissue masses were removed and histological examination revealed no organized testicular or ovarian morphology. Remnants of Fallopian tubes, epididymis, and clusters of Leydig cells were seen but no Sertoli cells were found. Endocrine studies showed levels of sex hormones consistent with primary gonadal failure. G-banding analysis of 16 blood lymphocytes revealed the karyotype 46,X,dicY(q11.2) in all cells. Varying proportions of X and Y centromeres in blood lymphocytes, skin fibroblasts, and in the incompletely formed Wolffian and Müllerian duct derivatives were demonstrated by FISH. Molecular studies confirmed the absence of most of the long arm of the Y chromosome and an intact short arm. The SRY gene was shown to be present, but we presume that due to the mosaicism the dose was insufficient to allow normal testicular development.

Genotype-phenotype associations in non-classical steroid 21-hydroxylase deficiency.

OBJECTIVE: To evaluate whether genotype differences can explain the clinical variability of non-classical steroid 21-hydroxylase deficiency (NC21-OHD) and to determine if genotype is related to ethnic origin. DESIGN: Genotyping for mutations in the steroid 21-hydroxylase (CYP21) gene was performed in 45 unrelated Israeli Jewish patients (nine males) with NC21-OHD (60min 17-hydroxyprogesterone (17-OHP), 45-386nmol/l) who were referred for evaluation of postnatal virilization or true precocious/early puberty. Eleven siblings diagnosed through family screening were genotyped as well. METHODS: Patients were divided by genotype into three groups: (A) homozygous or compound heterozygous for the mild mutations (V281L or P30L) (n=29; eight males); (B) compound heterozygous for one mild and one severe mutation (Q318X, I2 splice, I172N) (n=12; no males); (C) mild mutation detected on one allele only (n=4; one male; peak 17-OHP 58-151nmol/l). We then related the genotype to the ethnic origin, clinical phenotype and hormone level. Since group C was very small, comparisons were made between groups A and B only. RESULTS: At diagnosis, group B tended to be younger (5. 8+/-3.0 vs 8.1+/-4.3 years, P=0.09), had greater height SDS adjusted for mid-parental height SDS (1.6+/-1.1 vs 0.7+/-1.4, P=0.034), tended to have more advanced bone age SDS (2.9+/-1.5 vs 1.7+/-2.1, P=0.10) and had a higher peak 17-OHP level in response to ACTH stimulation (226+/-92 vs 126+/-62nmol/l, P<0.01). Group B also had pubarche and gonadarche at an earlier age (5.1+/-2.4 vs 7.4+/-2.2 years, P<0.01 and 7.4+/-1.8 vs 9.9+/-1.4 years, P<0.001, respectively) and a higher rate of precocious puberty (50 vs 17%, P=0.04). Stepwise logistic regression analysis (excluding males) yielded age at gonadarche as the most significant variable differentiating the two groups, with a positive predictive value of 86% for a cut-off of 7.5 years. CONCLUSIONS: The findings suggest that genotype might explain some of the variability in the phenotypic expression of NC21-OHD. Compound heterozygotes for one mild and one severe mutation have a higher peak 17-OHP associated with pubarche and gonadarche at an earlier age and more frequent precocious puberty. Hence, the severity of the enzymatic defect might determine the timing and pattern of puberty.

XY gonadal dysgenesis associated with the congenital nephrotic syndrome.

The occurrence of a nephrotic syndrome in a female infant with a 46,XY karyotype is reported. The internal genitalia were female but a microscopic region of immature testicular tissue was present in 1 of 2 streak gonads. The relationship of this child's abnormal genital differentiation to her renal disease is discussed in the light of reported cases of infantile nephritis and Wilms' tumor in male pseudohermaphrodites. It is suggested that a common teratogen operating on the embryonic urogenital ridge may cause both genital and renal anomalies.

Hyperprolactinemia after treatment of long-acting gonadotropin-releasing hormone analogue Decapeptyl in girls with central precocious puberty.

OBJECTIVE: To clarify the effects of prolonged treatment with long-acting GnRH analogue on serum PRL levels. DESIGN: Blood PRL levels were measured at 9 A.M. every 28 days for a period of 6 months. SETTING: Pediatric Endocrine Clinic, Hasharon Hospital, Petah Tiqva, Israel. PATIENTS: Thirteen girls with idiopathic central precocious puberty. RESULTS: Hyperprolactinemia developed in 5 of 13 girls after treatment with long-acting GnRH-a; mean blood PRL in all 13 girls rose significantly from 11.9 +/- 5.6 to 21.5 +/- 12.5 micrograms/L (mean +/- SD). CONCLUSIONS: The mechanism of hyperprolactinemia in our patients is unclear. It may have resulted from a decline in the release of the hypothalamic PRL inhibitory factor. Clinically, transient hyperprolactinemia during long-acting GnRH-a treatment for central precocious puberty also may reflect a constant depression of LH secretion.

Assessment of the hypothalamic-pituitary-testicular function in male patients with Wilson's disease.

Sixteen male patients with Wilson's disease were studied to detect potential endocrine dysfunctions. There was no clinical evidence of feminization in any of the patients, and the patient group spanned most pubertal stages. Gonadotropin, testosterone, sex hormone binding globulin (SHBG), dehydroepiandrosterone sulphate, androstenedione, estradiol, prolactin, cortisol, thyrotropin, and free thyroxine levels were determined. Low or borderline luteinizing hormone (LH) levels were present in most of the patients. In six of the adult patients, a standard gonadotropin-releasing hormone (GnRH) test was performed. Five of the six patients had blunted LH and follicle-stimulating hormone (FSH) responses to GnRH. Increased androgen levels were found in eight of the patients. Sex hormone-binding globulin was normal in eight of nine tested patients. Three single-dose human chorionic gonadotropin (hCG) stimulation tests of six adult patients showed normal responses. Three other patients who had elevated baseline levels responded with modest increases. Since liver disease is usually associated with decreased androgen levels, it is difficult to account for the elevated androgen levels. Both increased androgen levels and copper accumulation in the hypophysis could be responsible for the blunted GnRH response.

Melkersson-Rosenthal syndrome.

Four patients with recurrent upper lip and facial swelling and lingua plicata together with peripheral facial nerve palsy involvement were diagnosed as having Melkersson-Rosenthal syndrome. Because of the rarity of this syndrome in children, we present the results of follow-up evaluations of our patients and review the literature.

Preoperative treatment of intractable hyperthyroidism with acute lithium administration.

We present a 15-year-old girl with an unusual clinical course of intractable thyrotoxicosis that was resistant to thiocarbamide therapy and propranolol. Although the latter beta-adrenergic blocking agent has been used as the sole drug in the preparation of thyrotoxicosis patients for thyroidectomy, it was unsatisfactory for control of our case. In contrast, the patient's clinical response to lithium carbonate 900-1500 mg/d for 10 days was very good and no side effects were observed. This demonstrates the importance of lithium as the drug of choice in thyrotoxic emergencies and uncontrolled preoperative patients when rapid and safe inhibition of thyroid hormone secretion is required.

Extraordinary daytime urinary frequency in children.

BACKGROUND: Sudden onset of daytime urinary frequency of a small amount of urine in a previously toilet-trained child can be a disturbing problem. Psychosocial problems, problems at school, or problems within the family have to be taken into consideration. METHODS: Fifteen children with sudden onset of isolated daytime urinary frequency were evaluated and followed for a period of 12 to 18 months. A thorough medical and family history was obtained for each child, with special attention given to any psychosocial problems the child had experienced. All the children underwent a physical examination, complete urinalysis, and ultrasonography of the kidneys and bladder. RESULTS: In all of the patients, the urinalysis and ultrasonographic findings were within normal limits. A trigger factor was identified as the cause of urinary frequency in each case. CONCLUSIONS: Because urinary frequency is usually a benign self-limited condition, an extensive urological evaluation is not indicated. In most cases, providing reassurance to the parents and the child is the only intervention necessary.

Swimming and grommets.

BACKGROUND: Traditionally, children with tympanostomy ventilating tubes, or grommets, were advised that water should not enter their ears in order to prevent ear infections. This group of children has been considered somewhat handicapped regarding swimming. We conducted a prospective study to determine if there is a relation between suppurative otitis media and surface swimming in children with grommets. METHODS: Forty-two children with tympanostomy ventilating tubes were included in this study. Of the 42 children, 22 were swimmers and 20 were nonswimmers, who served as the control group. The age range was 3 to 12 years, and there was no difference in the age distribution between the groups. Surface swimming was allowed without earplugs or a bathing cap, although it was mandatory to use polymyxin B-neomycin-hydrocortisone eardrops at bedtime on the day of swimming. No diving was allowed. RESULTS: Three of 22 swimmers and 2 of 20 nonswimmers developed otorrhea. In 4 of the 5 children, the otorrhea was followed by an upper respiratory tract infection. In all cases, a bacterial culture revealed Pseudomonas. The ear drainage was easily controlled with local otic treatment in all the patients. CONCLUSIONS: Taking into consideration the possible risks of infection and bearing in mind the value and joy of swimming to children and parents, families should be reassured that surface swimming does not increase the risk of infection in children with tympanostomy tubes.