A patient with the classic features of Phelan‐McDermid syndrome and a high immunoglobulin E level caused by a cryptic interstitial 0.72‐Mb deletion in the 22q13.2 region

Abstract

Phelan-McDermid syndrome, also known as the 22q13 deletion syndrome, is a chromosomal microdeletion syndrome characterized by neonatal hypotonia, normal growth, profound developmental delay, absent or delayed speech, and minor dysmorphic features. Almost all of the 22q13 deletions published so far have been described as terminal. It is believed that the SHANK3 gene is the major candidate gene for the neurologic features of the syndrome. Here we describe a patient with a 0.72-Mb interstitial 22q13.2 deletion, intellectual disability, autistic behavior, epilepsy, mild dysmorphic features, and no deletion in the SHANK3 gene. The patient also has urticarial rash and an elevated level of immunoglobulin E, the latter has previously been described only once in a patient with monosomy 22q13.2-qter and SHANK3 gene deletion. To our knowledge, this is one of the smallest interstitial deletion in this region which has been published up to now. Although the patient has the classic phenotype of the 22q13 terminal deletion syndrome, the etiology for the neurologic and immunological features must be due to genes located more proximal to SHANK3 and this is also supported by other previously published cases of interstitial 22q13.2 deletions. The deleted area in our patient is gene-rich (26 genes), containing several known genes with different functions. Two of them-NFAM1 and TNFRSF13C are involved in immune system functioning. We suggest the haploinsufficiency of these genes might be related to hyper IgE syndrome in our patient.

A previously unrecognized 22q13.2 microdeletion syndrome that encompasses TCF20 and TNFRSF13C

“…In addition, two patients presenting with classic clinical features of PMS have been reported to have interstitial microdeletions in the 22q13.2 region that map proximal to the SHANK3 gene and the 950 kb minimally deleted region at 22q13.31 (Figure b) (Simenson, Õiglane‐Shlik, Teek, Kuuse, & Õunap, ; Thümmler et al, ). These deletions, located solely in the 22q13.2 region, span approximately 720 and 540 kb and encompass 15 and 14 OMIM genes, respectively.…”

Unilateral Opercular Polymicrogyria in a Girl with 22q13 Deletion Syndrome

“…Almost all of the 22q13 deletions published have been described as terminal [15,30,16,12,14,20]. However, there are several cases identified in the literature that have been described as 22q13 interstitial deletion and that presented a phenotype similar to the 22q13 terminal deletion syndrome [27,24,8,29]. These observations suggest that the etiology for the neurological features must also be due to genes located proximal to SHANK3.…”

Late-onset epileptic spasms in a patient with 22q13.3 deletion syndrome

“…Generalized tonic-clonic, myoclonic, absence, and focal seizures may occur in patients with 22q13.3 deletion syndrome. [2,[4][5][6][7][8]. Soorya et al reported that 13 of 32 (41%) patients with 22q13.3 deletion syndrome had clinical seizures, including seven (22%) with febrile seizures only, four (13%) with non-febrile seizures, and two (6%) with both febrile and non-febrile seizures [9].…”