Case Report: A Case Report and Literature Review of 3p Deletion Syndrome

Abstract

Objective: The aim of the present study is to explore the clinical and genetic characteristics of 3p deletion syndrome to improve clinicians' understanding of the disease.Methods: The clinical manifestations, process of diagnosis and treatment, and genetic characteristics of an individual case of 3p deletion syndrome were analyzed. CNKI, Wanfang Data, and the Biomedical Literature Database (PubMed) were searched. The search time limit, using “3p deletion syndrome” and “BRPF1” as keywords, was from the creation of the database up to June 2020. Related data were reviewed.Results: The proband was a male child with general developmental and intellectual disabilities, special facial features and congenital heart disease. The child was the parents' first pregnancy and first born. Gene microarray analysis showed a 10.095 Mb deletion in the 3p26.3-p25.3 region, resulting in a heterozygous mutation of the BRPF1 gene; thus, the patient was diagnosed with 3p deletion syndrome. At the time of diagnosis, the child was 1 year of age and was responding to comprehensive rehabilitation training. A total of 29 well-documented cases were found in the literature, of which 19 cases had an onset within 1 year of birth, and mainly manifested with mental and motor development disabilities and abnormal facial features, with different gene deletions, depending on the size and location of the 3p deletion.Conclusion: The genetic test results of the child in this study indicated a heterozygous deletion of the BRPF1 gene on the short arm of chromosome 3, which was a unique feature of this study, since it was rarely mentioned in other reports of 3p deletion syndrome. The clinical phenotype of this syndrome is complex as it can include intellectual and motor development backwardness, low muscle tone, certain abnormal facial features (low hairline, bilateral ptosis, widely spaced eyes, a forward nose, left ear auricle deformity, a high-arched palate, a small jaw), and the deformation of systems such as the gastrointestinal tract and the urinary tract malformation or symptoms of epilepsy. As clinical manifestations can be relatively mild, the syndrome is easy to miss or misdiagnose. Clinical workers need to be aware of this disease when they find that children have special features, such as stunted growth, low muscle tone or ptosis, and it needs to be diagnosed through genetic testing. Most children are able to develop certain social skills after rehabilitation treatment.

Intellectual developmental disorder with dysmorphic facies and ptosis caused by copy number variation including the BRPF1 gene in Peruvian patient

“…From the CNV perspective, 31 patients with interstitial and terminal deletions in chromosome 3p have been previously described with phenotypic characteristics like those presented by this patient. The characteristics of the 3p deletion syndrome (MIM #613792) are ID, motor delay, microcephaly, micrognathia, ptosis, long philtrum, polydactyly, hypotonia; heart, renal, and gastrointestinal anomalies; hypothyroidism, epilepsy, short stature, and risk of tumors [7,[31][32][33]. However, as it is a contiguous gene syndrome, the clinical characteristics will be variable and depend on the number of genes involved.…”

Porokeratotic eccrine ostial and dermal duct nevus associated with an 11 megabase 3p deletion

“…Our patient did not exhibit these features. Patients additionally can have dermatologic findings including hyperhidrosis, 9 recurrent rashes, 10 hypotrichosis, 11 hyperkeratosis, 12 and reticular hyperpigmentation 13 . No patient had confirmed or suggested PEODDN.…”

De novo 3p25-deletiós szindróma genotípus-fenotípus vizsgálata

“…Rövidítések aCGH = (microarray comparative genome hybridization) microarray-komparatív genomhibridizáció; CMA = (chromosomal microarray analysis) kromoszomális microarray-analízis; DNS = dezoxiribonukleinsav; EEG = elektroencefalográfia; FISH = fluoreszcens in situ hibridizáció; IUGR = (intrauterine growth restriction) méhen belüli növekedési elmaradás; LoF = (loss-offunction) funkcióvesztéses; Mb = megabázis; OMIM = (online Mendelian inheritance of man) a "Mendeli öröklődés emberben" projekt online adatbázisa; RMD = (rippling muscle disease) ritmikus mozgászavar; SNP = (single nucleotid polymorphism) egyszeres nukleotidpolimorfizmus; TBX1 = T-box transzkripciós faktor-1 A 3-as kromoszóma p-karjának distalis deletiójáról (3pszindróma, OMIM: 613792) a szakirodalom nagyon kevés információval rendelkezik. Mostanáig kevesebb mint 60 esetet publikáltak világszerte [1]. A kórkép leggyakoribb velejárói az alacsony születési súly, a microcephalia, a hypotonia, a növekedési és pszichomotoros retardáció, a ptosis és/vagy blepharophimosis és a congenitalis szívbetegség.…”

“…Egy másik, szintén központi szereppel bíró gén a BRPF1, melynek terméke egy kromatinregulátor, amely acetilálja a H3-hisztonok oldalláncait, s ezzel szintén számos gén transzkripcióját szabályozza, illetve az idegsejtek migrációját befolyásolja. A gén deletiója már önmagában is felelős az intellektuális fejlődési zavarok, a rendellenes arcvonások és a ptosis kialakulásáért [1].…”

“…Páciensünk hallásvesztésének hátterében az ATP2B2gén deletiója állhat. Az ATP2B2-gén LoF-mutációja autoszomális domináns öröklésmenetű, az érintetteknél gyors, progresszív, nagy frekvenciájú halláskárosodás figyelhető meg [1]. A normál hallású újszülötteknek általában 3-6 éves korukra lesz diagnosztizálható halláskárosodásuk.…”