Congenital disorder of glycosylation type Ix: review of clinical spectrum and diagnostic steps.

Congenital disorder of glycosylation type I (CDG I) represent a rapidly growing group of inherited multisystem disorders with 13 genetically established subtypes (CDG Ia to CDG Im), and a high number of biochemically unresolved cases (CDG Ix). Further diagnostic effort and prognosis counselling are very challenging in these children. In the current study, we reviewed the clinical records of 10 CDG Ix patients and compared the data with 13 CDG Ix patients published in the literature in search for specific symptoms to create clinical subgroups. The most frequent findings were rather nonspecific, including developmental delay and axial hypotonia. Several features were found that are uncommon in CDG syndrome, such as elevated creatine kinase or arthrogryposis. Distinct ophthalmological abnormalities were observed including optic nerve atrophy, cataract and glaucoma. Two subgroups could be established: one with a pure neurological presentation and the other with a neurological-multivisceral form. The first group had a significantly better prognosis. The unique presentation of microcephaly, seizures, ascites, hepatomegaly, nephrotic syndrome and severe developmental delay was observed in one child diagnosed with CDG Ik. Establishing clinical subgroups and increasing the number of patients within the subgroups may lead the way towards the genetic defect in children with a so far unsolved type of the congenital disorders of glycosylation. Raising awareness for less common, non-CDG specific clinical features such as congenital joint contractures, movement disorders or ophthalmological anomalies will encourage clinicians to think of CDG in its more unusual presentation. Clinical grouping also helps to determine the prognosis and provide better counselling for the families.

A girl with cutaneous hyperpigmentation, café au lait spots and ring chromosome 15 without significant deletion.

Ring chromosome 15 [r(15)] syndrome is characterised by specific facial features, café au lait spots, failure to thrive, mental retardation and typically with a terminal deletion of the long arm of chromosome 15. We report a 2.5 year old girl showing normal growth and development, large hyperpigmented skin changes showing hypopigmentated areas inside, multiple café au lait spots and premature graying-like hypopigmentation of scalp hair. She had a karyotype of r(15) in peripheral lymphocytes and fibroblasts. By FISH analysis the breakpoint was located distal to locus D15S936 (15q26.3) and within 300 kb of the end of the chromosome, indicating no deletion of functional genes on 15q. Hyperpigmentation and café au lait spots are rare signs in ring chromosome syndromes, but with r(15) syndrome, café au lait spots have been described in about 30% of patients and have been considered to result from the deletion of gene(s) on distal 15q. Based on the frequent observation of patchy hyperpigmentation with the r(15) syndrome, absent hyperpigmentation in cases of distal 15q deletion without a ring chromosome, and the telomeric breakpoint location in our patient indicating no significant deletion, we propose that the cutaneous hyperpigmentation and café au lait spots in our proband represent effects of the r(15) chromosome but are not caused by the deletion of specific gene(s) on distal 15q. Patchy skin hypopigmentation is a well known nonspecific sign in cytogenetic mosaicism which is commonly seen in ring syndrome.

[Kennedy disease in a patient with progressive speech disorder]. / Kennedy-betegség egy progresszív beszédzavarban szenvedó férfiben.

Kennedy disease is an adult onset neuromuscular disease characterized by slowly progressive proximal and bulbar muscle weakness. The disease associates with gynecomastia, adult onset infertility and sensory neuropathy, and caused by pathologic expansion of CAG repeats at the N-terminal region of the androgen-receptor gene at Xq11-q12. We report on a patient presenting with slowly progressive muscle weakness of the lower extremities, progressive dysartry and swallowing difficulties. The clinical symptoms were not fully specific for the disease. Moreover the family history was suggestive for an autosomal dominant trait meaning a diagnostic pitfall at the original examination. Finally the firm diagnosis of the Kennedy disease was established by a polimerase chain reaction based method.