Another patient with an interstitial deletion of chromosome 9: case report and a review of six cases with del(9)(q22q32).

We report a case of del(9)(q22q32) in a severely mentally retarded boy. The most prominent clinical features are short stature, microcephaly, dysmorphic facies, and delayed bone age. Although six cases of this deletion have now been reported, confirmation of a definite syndrome is not yet possible.     

Atypical phenotype associated with deletion (15) (pter → q11::q13 → qter)

We report on a 10-year-old boy with an interstitial deletion within the region of bands 15q11 → q13. Authors have associated the manifestation of the Prader-Willi syndrome (PWS) with variable deletions involving the bands q11 → q13. Our patient had atypical manifestations not usually associated with PWS, ie, normal stature, proportionally sized hands and feet, normal genitalia, and was nonambulatory and severely mentally retarded. This case emphasized the clinical diversity seen in proximal 15q deletions in the region considered to be correlated with the PWS.     

Atypical phenotype associated with deletion (15) (pter----q11::q13----qter)

We report on a 10-year-old boy with an interstitial deletion within the region of bands 15q11----q13. Authors have associated the manifestation of the Prader-Willi syndrome (PWS) with variable deletions involving the bands q11----q13. Our patient had atypical manifestations not usually associated with PWS, ie, normal stature, proportionally sized hands and feet, normal genitalia, and was nonambulatory and severely mentally retarded. This case emphasized the clinical diversity seen in proximal 15q deletions in the region considered to be correlated with the PWS.     

Syndromes associated with deletion of the long arm of chromosome 18[del(18q)].

We studied eight persons whose karyotypes demonstrated deletion of a portion of the long arm of chromosome 18. Seven of these persons who showed the typical del(18q) syndrome had a common deletion in band 18q21, most likely band q21.3, and in at least two persons the deletion was interstitial. Another mentally retarded child, dissimilar in appearance, had a more proximal deletion within band 18q12. Two different clinical syndromes resulted from deletions of these different segments of the long arm of chromosome 18.     

Interstitial deletion, del(4)(q12q21.1), owing to de novo unbalanced translocation in a 2 year old girl: further evidence that the piebald trait maps to proximal 4q12.

A very short, microcephalic, and mentally retarded 2 year old girl showed minor anomalies including prominent occiput, delayed closure of the anterior fontanelle, high frontal hairline, prominent ears, upward slanting palpebral fissures, a small nose with bulbous tip, delayed tooth eruption and bone maturation, and short and tapering fingers and toes. She did not have a white forelock. Cytogenetic investigation disclosed a de novo unbalanced translocation between chromosomes 4 and 18 with deletion of 4q12-->q21.1. Molecular investigation showed lack of a paternal allele for the microsatellite markers D4S392 and D4S398. This case shows indirect evidence that the piebald gene maps to proximal 4q12.     

Interstitial deletion of chromosome 18[del(18)(q11.2q12.2 or q12.2q21.1].

A 27-month old boy with mild developmental delay, growth delay, strabismus, midface hypoplasia, relative telecanthus, downslanting palpebral fissures, epicanthal folds, dental hypoplasia, and cardiac defects was found to have an interstitial deletion of chromosome 18 involving band q12.1 or q12.3     

Syndromes associated with deletion of the long arm of chromosome 18[del(18q)]

We studied eight persons whose karyotypes demonstrated deletion of a portion of the long arm of chromosome 18. Seven of these persons who showed the typical del(18q) syndrome had a common deletion in band 18q21, most likely band q21.3, and in at least two persons the deletion was interstitial. Another mentally retarded child, dissimilar in appearance, had a more proximal deletion within band 18q12. Two different clinical syndromes resulted from deletions of these different segments of the long arm of chromosome 18.     

Endocrine abnormalities in a patient with partial trisomy 4q.

Partial trisomy of the long arm of chromosome 4, usually resulting from a familial segregation of a balanced translocation, has been described in a number of patients. This report describes the genetic and endocrine findings in a 16 year old 46,XY,12q+ mentally retarded male. The banding pattern of the extra chromatin material from this de novo unbalanced translocation shows that the distal segment of the long arm of chromosome 4 is involved. Comparison of the clinical features in this patient with cases of partial trisomy 4q previously reported support the cytogenetic evidence for this translocation involving the distal portion of 4q. Endocrine data suggested an end-organ resistance, characterised by extreme hyperinsulinaemia, primary hypothyroidism, and hypergonadotrophic hypogonadism associated with no signs of autoimmunity. To our knowledge, no endocrine evaluation has been previously reported in patients with partial trisomy 4q.     

De novo 3q/7q translocation and associated interstitial 7q35 deletion

In the present report we describe a severely mentally retarded and dysmorphic female child with a de novo 3q/7q reciprocal translocation and loss of band 7q35. This finding supports the hyothesis that the occurrence of mental retardation and/or congenital malformations in de novo autosomal reciprocal translocation may be due to the loss of a small amount of chromatin material during this chromosomal rearrangement.     

Interstitial deletion 2q32.1----q34 in a child with half normal activity of ribulose 5-phosphate 3-epimerase (RPE).

High resolution banding analysis showed a de novo interstitial deletion, 46,XX, del(2) (q32.1q34), in a malformed and severely mentally retarded girl aged nine years. Biochemical studies showed that the proband had half normal activities of both erythrocyte isocitrate dehydrogenase (IDH1) and ribulose 5-phosphate 3-epimerase (RPE). It is suggested that the gene for RPE is located on the segment 2q32.1----q34.     

Interstitial deletion, del(4)(q33q35.1), in a mother and two children.

The inheritance of autosomal deletions from affected parents has only rarely been reported. We report an unbalanced interstitial deletion, del(4)(q33q35.1), in a mother and two male offspring. The mother and older sib are mentally retarded but have only mild dysmorphic features. The younger sib, at five months, is showing signs of developmental delay. All three patients show some abnormalities in common with cases that have terminal deletions of 4q with breakpoints at 4q33, but in general exhibit less severe abnormalities. The family illustrates the importance of detailed cytogenetic analysis of children with developmental delay who do not display major dysmorphic features.     

Meiotic segregation in familial reciprocal translocation t(8q;22q)

We studied the chromosomes of a mentally retarded boy with minor anomalies and of his parents using a G-band stained high-resolution chromosome method. This documented dup (8q24.1 → 8qter) and dup(22pter → 22q11.2) in the boy due to a maternal balanced reciprocal translocation of chromosomes 8 and 22 and 3:1 disjunction during meiosis I. The karyotype of the boy is 47, XY, + der(22) (22pter → 22q11.2::8q24.1 → 8qter). The der(22) was involved in satellite associations and stained positively with AgNO₃ in mother and child. The case is compared to similar cases in the literature and the function of the small acrocentric marker chromosome during meiosis is discussed.     

Adult with an interstitial deletion of chromosome 10 [del(10)(q25. 1q25.3)]: overlap with Coffin-Lowry syndrome

We recently evaluated a mentally retarded 48 year old man found to have a cytogenetic deletion of chromosome 10 [46,XY,del(10) (q25. 1q25.3)]. Of interest, he shares many clinical findings with those described in Coffin-Lowry syndrome (CLS). These include severe mental retardation, short stature and a coarse facial appearance with widely spaced eyes, and patulous lips. He also had an extra transverse hypothenar crease, a finding that is seen in CLS. Furthermore, he has characteristic radiographic hand findings described in 95% of patients with CLS. The CLS gene, located at Xp22. 2, has recently been identified, and mutations in the Rsk-2 gene have been identified in several CLS patients. Rsk2 is part of a gene family implicated in cell cycle regulation through the mitogen-activated protein (MAP) kinase cascade. None of the currently recognized components of this pathway maps to the region deleted in our patient, nor are we able to identify any likely candidate genes in the deleted region, although several G protein coupled receptors have been cloned from the region. This patient's findings have some overlap with those seen in CLS, suggesting that a gene involved in MAP kinase signaling may be present in the deleted region of chromosome 10q25.1-25.3. Patients with a phenotype consistent with CLS, but lacking a family history suggestive of an X-linked disorder, should be evaluated with chromosome analysis paying particular attention to the region 10q25.     

Paracentric inversion of the X chromosome [inv(X)(q12q28)] in familial FG syndrome.

FG syndrome is an X-linked incomplete recessive condition comprising mental retardation, congenital hypotonia, macrocephaly, a distinctive facial appearance, and constipation or anal malformations. Here, we report on a chromosome X inversion [inv(X)(q12q28)] in a boy with FG syndrome and in his mentally retarded maternal uncle, and we discuss the possible involvement of this paracentric inversion in the FG syndrome.     

Deletion of chromosome region 18q21.1 --> 18q21.3 in a patient without clinical features of the 18q- phenotype

In a 16-month-old boy referred because of developmental delay and asymmetric motor development, chromosome analysis showed an aberrant chromosome 18 in all 25 metaphases examined. The chromosome aberration was initially interpreted either as an interstitial deletion of chromosome region 18q21.1 --> 18q21.3 or an unbalanced translocation involving the distal part of the long arm of chromosome 18. Chromosome microdissection in combination with fluorescence in situ hybridization demonstrated that the aberrant chromosome 18 had an interstitial deletion, the karyotype being: 46,XY,del(18)(q21.1q21.3). At age 27 months, his development was moderately retarded. He showed craniofacial asymmetry but no other anomalies. The clinical and cytogenetic findings are compared with previously reported patients with a terminal or interstitial deletion in the long arm of chromosome 18.     

Mosaicism for a tandem duplication dup(1)(q12q22) in an 18 year old female.

The clinical features and cytogenetic results of an 18 year old mentally handicapped female found to be a mosaic for a tandem duplication of chromosome 1 (46,XX,dup(1)(q12q22)/46,XX) are reported. The case is compared with the three previously described cases and possible mechanisms for the origin of the duplication are discussed. This patient was not found to have features of Proteus syndrome which was previously reported in a subject mosaic for a tandem duplication involving chromosome (1)(q11q25).     

Deletion mapping of a retinal cone-rod dystrophy: assignment to 18q211

Deletion of 18q211 was observed in a mentally retarded young man with electrophysiologically demonstrated cone-rod dystrophy, present since childhood. He had hypogonadism and a central postsynaptic hearing impairment. This is the first case of a chromosome deletion in a patient with a cone-rod dystrophy. Three patients with more distal deletions on chromosome 18 did not present retinal dystrophies. We suggest that one of the loci for cone-rod dystrophy may be located on chromosome 18 at q211-213. Reports of similar findings will be necessary for confirmation of this assumption.     

Angelman syndrome with a chromosomal inversion 15 inv(p11q13) accompanied by a deletion in 15q11q13.

A family is described in which an inversion of chromosome 15, 15 inv(p11q13), is segregating. All family members are healthy except the proband who is a 10 year old boy with Angelman syndrome. Although the chromosomal inversion has been passed from the grandfather to both his son and his daughter with no ill effect, passage from daughter to grandson has resulted in a deletion of chromosome 15 material which is presumed to be the cause of Angelman syndrome in this boy. The probabilities of an inversion of this type being instrumental in causing the syndrome are discussed.     

De novo 21q interstitial deletion in a retarded boy with ulno-fibular dysostosis

A 9-year-old boy was referred for evaluation of multiple anomalies and mental retardation. Skeletal abnormalities had been noted at birth: joint contractures, right acetabular "dysplasia," ulno-fibular dysostosis, and bilateral talipes equinovarus with calcaneocuboid fusion. Additional findings at 9 years included short stature, unusual facial appearance, camptodactyly of several digits, undescended testes, and syndactyly of toes 4 and 5. On psychological testing he was found to be moderately retarded. Cytogenetic analysis of chromosome bands using Q, GTG, R, and C banding showed an interstitial deletion of 21q; karyotype designation: 46,XY, del (21)(pter----q11.2::q22.1----qter). Parental chromosomes were normal. Manifestations in this boy, including the joint contractures, are similar to those described in the monosomy 21 syndrome. Ulno-fibular dysostosis has not been reported previously with abnormalities of chromosome 21. To our knowledge, this is the second patient reported with an interstitial deletion of chromosome 21, and the patients are phenotypically dissimilar.     

Another patient with a de novo deletion further delineates the 2q33.1 microdeletion syndrome

A male patient, who had intra-uterine growth retardation, a low birth weight and hypotonia due to a chromosome 2q33.1 deletion, is described. At the age of 20 years, he displays short stature, microcephaly, a high forehead, microstomia, large teeth and is hypertonic. He is severely mentally retarded, has not developed speech, is hyperactive, anxious and at times aggressive. Full tiling array showed a de novo 14 Mb deletion at chromosome region 2q32.3q33.2, further delineating the 2q33.1 microdeletion syndrome.