18q-Syndrome with coeliac disease

Abstract

Sir: We report on a male patient of normal birth weight and length with a deletion of 18q21.31-qter. He presented with congenital hips subluxation, inguinal hernia, sublingual frenulum and prognathism. His ®rst months of life were characterized by frequent vomiting and drooling. His staturo-ponderal evolution followed the 3rd percentile except for a decline during the period preceding the diagnosis of coeliac disease at the age of 1 year. His adult height is 161 cm (mid-parental height is 158 cm). At the age of 1 year he developed clinically visible steatorrhoea. A gastro-intestinal work up showed coeliac disease according to the ESPGAN standard of three jejunal biopsies for diagnosis.His psychomotor development was slow. He walked alone at the age of 20 months. Psychological testing at the age of 4 years showed a real desire for communication with only short sentences of two words despite repetitive autistic behaviour. Playing was symbolic and relational. At the age of 10 he showed a verbal intelligence quotient (VIQ) of 97, a practical intelligence quotient (PIQ) of 87 and a total intelligence quotient (TIQ) of 90 on the Wechsler intelligence scale for children (WISC). At the age of 18 years a complete re-evaluation showed a VIQ of 97, a PIQ of 82 and a TIQ of 89 using the Wechsler Adult Intelligence Scale.Neurological examination showed a cerebellar syndrome (hypotonia, tremor and dysarthria). A CT scan of the brain performed at the age of 3 years revealed a small cerebellar caudal volume and enlarged ventricles. MRI at the age of 9 years con®rmed the cerebellar ®ndings. Further MRI at the age of 18 years showed a prominent cisterna magna, broad vallecula and small but normal cerebellar tonsils. The foramen of Magendie was relatively broad. He had sporadic short episodes of conscience loss without pathognomic signs of epilepsy on EEG. The visual evoked potentials showed a prolonged latention time.Cytogenetic analysis showed a deletion of the long arm of chromosome 18q. The karyotype was 46, XY, del(18) (q21.31-qter) (Fig. 1b). Since the basic myelin protein (MBP) gene is located in 18q22-qter, molecular analysis of a polymorphic marker in the MBP gene was performed. The paternal copy of the MBP gene was deleted. This was a de novo deletion as the father had two MBP copies. Fluorescence in-situ hybridisation with a total chromosome 18 paint probe (Fig. 1a,d) excluded the possibility of a translocation of the missing chromosome 18q region to another chromosome.A special feature in this case is the IQ which is higher than the IQ range found in the literature (73A<40) [2]. The variations seen in myelinization [1], evoked potentials and intelligence quotient, suggest that the MBP absence in the peripheral nervous system in the 18q-syndrome does not appear to have a clear functional eect.This is the ®rst time that an association has been observed between an 18q-syndrome and coeliac disease. It is unclear whether this is a casual association or whether chromosome 18q harbours a gene that plays a role in the pathogene...

Primary immunodeficiency associated with chromosomal aberration – an ESID survey

“…Although patients with complete 10p trisomy are not reported to have immunodeficiency [ 36 , 37 ], patients with terminal deletions of 10p have been reported with IgA- and IgG-deficiency before [ 21 , 38 ]. The 18q − syndrome is associated with IgA-deficiency and other autoimmune or immunodeficiency diseases, such as common variable immunodeficiency (CVID) [ 39 ], juvenile rheumatic arthritis [ 40 ], insulin-dependent diabetes mellitus [ 41 ], celiac disease [ 42 ] and thyroid hormone abnormalities [ 43 ]. This partly matches the clinical phenotypes of our related patients.…”

18q deletions: Clinical, molecular, and brain MRI findings of 14 individuals

“…IgA deficiency has been reported in about one quarter of individuals with 18q deletions [Cody et al, 1999]. In addition, there are case reports of other autoimmune disorders, including cases with celiac disease [Lipschutz et al, 1999], hypothyroidism [Faed et al, 1972], progressing vitiligo [Weiss et al, 1991], juvenile rheumatoid arthritis [Rosen et al, 2004], and early‐onset IDDM [Dacou‐Voutetakis et al, 1999]. In the present study, four patients had disorders, which are probably autoimmune in origin, including IgA deficiency, hypothyroidism, iritis, and alopecia.…”

Primary Immunodeficiency Associated With Chromosomal Aberration – An Esid Survey

“…Although patients with complete 10p trisomy are not reported to have immunodeficiency [36,37], patients with terminal deletions of 10p have been reported with IgAand IgG-deficiency before [21,38]. The 18q − syndrome is associated with IgA-deficiency and other autoimmune or immunodeficiency diseases, such as common variable immunodeficiency (CVID) [39], juvenile rheumatic arthritis [40], insulin-dependent diabetes mellitus [41], celiac disease [42] and thyroid hormone abnormalities [43]. This partly matches the clinical phenotypes of our related patients.…”