Rheumatoid arthritis in the 46, XX, 18p- syndrome

Some of the evidence suggesting a relationship between autoimmunity and chromosomal aberrations is reviewed and an example which may support such a relationship is presented. The propositus was a 5-year-old Caucasian female who had juvenile rheumatoid arthritis and a deletion of the short arm of a chromosome 18 (46, XX, 18p-). Her serum I_KA was normal, although I_gA deficiency has been reported in a significant number of patients having an 18 deletion syndrome as well as in patients having rheumatoid arthritis. This patient focuses attention on the presently unresolved problem of the association between autoimmune disease and chromosomal aberrations.     

Prenatal recognition of 4p- syndrome.

A fetus with the rare 4p- syndrome was detected by chromosome analysis of amniotic cell culture, and the pregnancy terminated. The fetus showed a number of the physical stigmata of the syndrome.     

Familial 5p- syndrome

This report concerns a mother and son with a small terminal deletion of the short arm of chromosome 5 (del(5)(qter → pi5.1:). Both mother and son had superficial resemblance to patients with classical Cri-du-Chat Syndrome, but lacked the severe mental and growth retardation generally associated with such cases.     

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure.

A 35-month-old black boy with Hallermann-Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T4 and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be somewhat altered due to his racial back-ground. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.     

Towards mapping phenotypical traits in 18p- syndrome by array-based comparative genomic hybridisation and fluorescent in situ hybridisation

Molecular karyotyping holds the promise of improving genotype-phenotype correlations for frequent chromosome conditions such as the 18p- syndrome. In spite of more than 150 reported cases with deletions in 18p, no reliable phenotype map for the characteristic clinical findings such as mental retardation, post-natal growth retardation and typical facial features has been established yet. Here, we report on four patients with partial monosomy 18p of different sizes owing to unbalanced translocations that were thoroughly characterised clinically and by molecular karyotyping. One patient had a terminal deletion of 1.6 Mb in 18p and a trisomy of 8q24.23-qter as determined by array-based comparative genomic hybridisation and large insert clone fluorescent in situ hybridisation. In two sibs and a fourth patient, cytogenetic and molecular-cytogenetic analyses showed the terminal deletions in 18p (8.0 and 13.84 Mb, respectively) to be accompanied by partial trisomies of 20p. Literature analyses of typical phenotypic features of 18p-, 8q+ and 20p+ syndromes allowed the attribution of clinical findings in our patients to the respective chromosomal aberration. Based on these data, we propose a phenotype map for several clinical features of the 18p- syndrome: Round face was tentatively mapped to the distal 1.6 Mb of 18p; post-natal growth retardation and seizures to the distal 8 Mb and ptosis and short neck to the proximal half of 18p.     

CALL gene is haploinsufficient in a 3p- syndrome patient.

The 3p- syndrome results from deletion of a terminal segment of the short arm of one chromosome 3 (3p25-->pter), and is characterized by multiple congenital anomalies and mental retardation. Due to its variable expression, it is assumed this disorder is a contiguous gene syndrome with an undefined number of genes contributing to the phenotype. In an effort to discover genes contributing to mental defects in 3p- syndrome, we determined whether the CALL gene, mapped to 3p26.1 and coding for a neural recognition molecule, is deleted in a boy with this disorder. We found that the break in this patient is distal to the VHL gene, removing D3S18 and the CALL loci. The deletion of one copy of the CALL gene might be responsible for mental defects in patients with 3p- syndrome. Am. J. Med. Genet. 86:482-485, 1999. Published 1999 Wiley-Liss, Inc.     

The Wolf-Hirschhorn (4p-) syndrome

In a review of 43 cases, the phenotypic spectrum of the Wolf-Hirschhorn syndrome is analyzed and the frequency of clinical anomalies is tabulated. The characteristic features are intrauterine growth retardation, severe psychomotor retardation, typical facies, and various major and minor congenital anomalies suggestive of a midline fusion defect. Diagnosis is established by karyotyping - deletion of the short arm of chromosome No. 4. All cases so far reported are de novo occurrences with no sibling involvement and normal parents. Prognosis is poor, with death in the first 2 years of life in 34 % of cases, usually due to cardiac decompensation or infection. Psychomotor retardation is profound, so that heroic medical efforts probably need to be reconsidered.     

Turner's syndrome with concomitant hypopituitarism: case report

The unique case of a young woman with concomitant pituitary insufficiency and gonadal dysgenesis due to Turner's syndrome is described. At the age of 17 years, when first examined elsewhere, this patient was prepubertal and short and a diagnosis of growth hormone deficiency was made. One year later, while on growth hormone (GH) substitution, thyrotrophin deficiency and hypogonadotrophic hypogonadism were confirmed and thyroxine and sex steroid substitution therapy was initiated. Upon evaluation in our clinic, at the age of 30 years, the low final height achieved with the GH substitution therapy, a number of clinical characteristics and the absence of ovarian tissue on ultrasound led to examination of the patient's karyotype, which revealed concurrent gonadal dysgenesis due to Turner's syndrome. This case illustrates that the co-existence of primary and secondary hypogonadism may obscure and delay the diagnosis of Turner's syndrome, a diagnosis which alters the counselling of the patient from the reproductive perspective.     

Hallermann-Streiff syndrome with hypopituitarism contributing to growth failure

A 35-month-old black boy with Hallermann–Streiff syndrome (HSS) was evaluated for anterior hypopituitarism when he presented with ketotic hypoglycemia, microgenitalia, and short stature. Endocrine evaluation showed a low T₄ and TSH levels, suggesting hypothalamic hypothyroidism; this was confirmed by TRH stimulation. Metyrapone test confirmed ACTH deficiency as a contributing factor to the ketotic hypoglycemia. A superagonist GnRH test suggested hypothalamic GnRH deficiency. Growth hormone provocative testing conclusively demonstrated complete growth hormone deficiency. MRI investigation of the brain suggested hypopituitarism. Although facial findings were not completely classical of the HSS, we suggest these may be some what altered due to his racial background. We recommend endocrine evaluation of HSS patients with manifestations suggesting hypopituitarism since treatment of this condition will improve the quality of life of these patients.     

Trisomy 18 syndrome with cleft foot.

Ectrodactyly of the feet has been reported only twice in association with trisomy 18 syndrome. A severe form of this anomaly, the first with published illustrative x rays, is described in a male infant with trisomy 18 syndrome. It is suggested that this may represent an extreme expression of the foot anomalies more commonly associated with this syndrome.     

Neurologic manifestations in 18q- syndrome.

We report a mother and son with a deletion at 18q22.3. Both have the typical manifestations of the 18q- syndrome. In addition, both have an action tremor which became apparent in childhood. The mother subsequently developed chorea and dysmetria in late adolescence. Magnetic resonance imaging of their brains showed poor myelination of the central white matter tracts with relatively normal myelination of the corpus callosum. We propose that these neurologic findings are most likely due to a failure of expression of the myelin basic protein gene.     

Intrasellar paraganglioma associated with hypopituitarism.

A 37-year-old with a history of postpubertal arrest of sexual development and delayed growth was found to have an enlarged sella turcica. The clinical and biochemical features were consistent with hypopituitarism. A tumor was removed transsphenoidally that, through light microscopy, histochemistry, and electron microscopy, proved to be a paraganglioma. We report the possible origin of intrasellar paraganglioma, as well as the pathogenesis of hypopituitarism.