Interstitial deletion of chromosome 4, del(4)(q12q21.1), in a child with multiple congenital abnormalities.

Abstract

Deletions of. the distal region of the long arm of chromosome 4 are well documented and characterised, whereas deletions ofthe proximal region are apparently rare. We report another child with a proximal interstitial deletion of chromosome 4, del(4)(q12q21.1), and multiple congenital anomalies, including bilateral colobomata, which has not previously been described in patients with similar deletions.The proband was the second child of a 22 year old mother and 47 year old father who were healthy and unrelated. He has three sibs and five half sibs, all phenotypically normal. Delivery was at 41 weeks after an unremarkable pregnancy. There was fetal distress during the second stage, but a spontaneous vaginal delivery occurred before obstetric intervention could be arranged. Apgar scores were 9 and 10 at one and five minutes respectively. Birth weight was 3240 g (10th centile), length 52 cm (50th centile), and head circumference 35-5 cm (50th centile).The baby was referred for cytogenetic investigation on day 14 because of abnormal facial appearance, poor feeding, and an apnoeic episode. He was noted to be hypotonic and to have bilateral iris colobomata. Further ophthalmic examination showed right microphthalnia with a coloboma involving the optic disc and macula. The coloboma on the left involved part of the optic disc with sparing of the macula. Additional dysmorphic features were a high arched palate and widely spaced nipples. He had a transient heart murmur. Skull and spinal x rays, CT scan, and ultrasound examination of the head showed no further abnormalities.His growth and development have been delayed and on re-examination at 3 years 10 months his head circumference and weight had fallen below the 3rd centile. His head was an unusual shape with bitemporal narrowing and sparse hair (fig 1). He sat with support but had developed a scoliosis. He had a persistent nasal discharge although there was no evidence of choanal atresia. He had bilateral deafness but responded to loud low notes.Cytogenetic analysis of a peripheral blood sample using GTG and RBG banding indicated an interstitial deletion of the proximal region of the long arm of chromosome 4 (fig 2). The karyotype was interpreted as 46,XY,del(4)(pter-qql2::q21.1--qter). Parental karyotypes were normal.

Interstitial deletion of chromosome 4, del(4)(q12q21.1), in a mentally retarded boy with a piebald trait, due to maternal insertion, ins(8;4)

“…Pigmentary changes were not found in 3 of the 8 patients summarized in Table I. The patients of Lech et al [1982], Beall et al [1988], and Curtis et al [1990] were free of the piebald trait. Because 4q12 is a large unstained band, the deletion in these 3 patients may be distal to the location of the piebald gene.…”

“…Only 7 children with proximal deletion involving a segment from bands 4q12 to 4q21 have been described [Beall et al, 1988;Curtis et al, 1990;Funderburk and Crandall, 1974;Hoo et al, 1986;Lacassie et al, 1977;Lech et al, 1982;Yamamoto et al, 1989]. The deletion occurred as a de novo interstitial deletion in all cases except in the patient reported by Funderburk and Crandall [1974], who had an intercalary deletion and a de novo reciprocal translocation.…”

4q12–4q21.21 deletion genotype–phenotype correlation and the absence of piebaldism in presence of KIT haploinsufficiency

“…A review of the literature identified four other patients who were hemizygous for KIT and lacked piebaldism [Lech et al, 1982;Beall et al, 1988;Curtis et al, 1990;Schinzel et al, 1997]. Consistent with incomplete penetrance of KIT haploinsufficiency in piebaldism is the report of decreasing severity of piebaldism throughout the life of a patient with Waardenburg syndrome [Chang et al, 1993].…”

“…Joint Laxity Neurological Hypotonia Patients: (1) [Chen et al, 2011]; (2) [Slavotinek and Kingston, 1997]; (3) [Funderburk and Crandall, 1974]; (4) [Lech et al, 1982]; (5) [Thiel et al, 2000]; (6) [Beall et al, 1988]; (7) [Curtis et al, 1990]; (8) [Fujimoto et al, 1998]; (9) [Hoo et al, 1986]; (10) [Hsu et al, 1998]; (11) [Schinzel et al, 1997]; (12) [Sijmons et al, 1993]; (13) [Yamamoto et al, 1989]. Abn, abnormal; DD, developmental delay; GER, gastroesophageal reflux; ID, intellectual disability; LO, lens opacities; MCD, motor coordination difficulties; MD, motor development; NA, not applicable; NR, not reported, PF, palpebral fissures; Post, posteriorly; PT, peripheral tone; TR, tendon reflexes; OM, obliquus muscle.…”

“…To the best of our knowledge, only 13 cases of proximal 4q interstitial deletions, with a breakpoint in 4q12 have been reported in the literature [Funderburk and Crandall, 1974;Lech et al, 1982;Hoo et al, 1986;Beall et al, 1988;Yamamoto et al, 1989;Curtis et al, 1990;Sijmons et al, 1993;Schinzel et al, 1997;Kingston, 1997;Fujimoto et al, 1998;Hsu et al, 1998;Thiel et al, 2000;Chen et al, 2011].…”