DiGeorge syndrome (DGS) comprises thymic hypoplasia, hypocalcaemia, outflow tract defects of the heart, and dysmorphic facies. It results in almost all cases from a deletion within chromosome 22q11. We report the clinical findings in 44 cases. We propose that DiGeorge syndrome should be seen as the severe end of the clinical spectrum embraced by the acronym CATCH 22 syndrome; Cardiac defects, Abnormal facies, Thymic hypoplasia, Cleft palate, and Hypocalcaemia resulting from 22q11 deletions.

/pdf/digeorge-syndrome-part-of-catch-22-36qwo2b4yn.pdf

DiGeorge syndrome: part of CATCH 22.

Two cases of Noonan syndrome are observed. The Noonan syndrome is a Turner-like syndrome with normal chromosomal constitution. Essential criteria in diagnosing the syndrome are the facial expression (hyper-telorisme, low-set and malformed ears, micrognathie, fish-like mouth). The short webbed neck and the cubitus valgus. These children are rather small and mental retardation can be present, especially in comparison with their siblings. Associated cardiac malformations occur in approximately 50% of the cases. We insist on audiologic findings. One case has a hearing impairment due to a malformation of the middle ear, recognised radiologically. The other has a deafness of perception type. Yet, the familial occurrence of last patient makes it doubtful whether this hearing loss can be linked to the Noonan-syndrome.

The Noonan syndrome

Noonan syndrome is characterized by typical facies, short stature and congenital cardiac defects. Approximately half of all cases are sporadic, but autosomal dominant inheritance with variable expression is well established. We have performed a genome-wide linkage analysis in a large Dutch kindred with autosomal dominant Noonan syndrome, and localized the Noonan syndrome gene to chromosome 12 (Zmax=4.04 at θ=0.0). Linkage analysis using chromosome 12 markers in 20 smaller, two-generation families gave Zmax=2.89 at θ=0.07, but haplotype analysis showed non-linkage in one family. These data imply that a gene for Noonan syndrome is located on chromosome 12q, between D12S84 and D12S366.

Mapping a gene for Noonan syndrome to the long arm of chromosome 12

We describe the largest Noonan syndrome (NS) family reported to date. The manifestations of the affected relatives are discussed. In the absence of a biochemical marker NS is still a clinical diagnosis. The diagnostic criteria that were used are presented compared with other published criteria for diagnosing NS. The large size of this family enabled us to test the possible involvement of candidate regions by multipoint linkage analysis. Both the region surrounding the NF1 locus on chromosome 17 and the proximal part of chromosome 22 could be excluded. Since NS may well be heterogeneous, the use of such a large family in linkage studies of NS should prove indispensable.

Clinical and molecular studies in a large Dutch family with Noonan syndrome

Defining the Clinical Spectrum of Deletion 22q11.2

A boy with the dysmorphic features of Noonan's syndrome and pulmonary valve stenosis who had evidence of hypoparathyroidism and abnormal T lymphocyte numbers in the neonatal period is reported. He had a normal karyotype but molecular analysis revealed a submicroscopic deletion within chromosome 22q11, the region deleted in DiGeorge syndrome. Thus this child has both Noonan's syndrome and DiGeorge syndrome; 22q11 is a candidate region for a gene defective in Noonan's syndrome.

https://adc.bmj.com/content/archdischild/68/2/187.full.pdf

S Strobel

Papers

Noonan's and DiGeorge syndromes with monosomy 22q11.