Brain anomalies, retardation of mentality and growth, ectodermal dysplasia, skeletal malformations, Hirschsprung disease, ear deformity and deafness, eye hypoplasia, cleft palate, cryptorchidism, and kidney dysplasia/hypoplasia BRESEK/BRESHECK: New X-link

Mowat-Wilson syndrome (MWS) is a rare autosomal dominant syndrome characterized by distinctive facial features, congenital heart defects, Hirschsprung disease, genitourinary anomalies, various structural brain anomalies, and intellectual disability. Pathogenic mutations that result in haploinsufficiency in the ZEB2 gene cause MWS. In this study, we aimed to evaluate the clinical features and molecular analysis results of 4 MWS patients. All patients were examined by an expert clinical geneticist. Dysmorphological abnormalities were recorded. Data including demographic, clinical, and laboratory findings were obtained from hospital records. ZEB2 gene analysis was performed using a Sanger sequencing method. All patients had typical facial features of MWS such as widely spaced eyes, broad eyebrows with a medial flare, low-hanging columella, prominent or pointed chin, open-mouth expression, and uplifted earlobes. Four different heterozygous mutations were identified; 2 mutations were frameshift (c.246_247delGGinsC, c.980_980delG), 1 was nonsense (c.2083C>T), and 1 was splice site (c.808–2A>G). Two of them (c.246_247delGGinsC, c.980_980delG) have not been previously reported in the literature. By defining 2 novel mutations, this study contributes to the molecular spectrum of MWS, while also providing a further insight for genetic counseling. It also demonstrates the importance of dysmorphological examination in clinical diagnosis.

Download Full-text

Total colonic aganglionosis and cleft palate in a newborn with Janus-cysteine 618 mutation of RET proto-oncogene: a case report

Italian Journal of Pediatrics ◽

10.1186/s13052-020-00901-9 ◽

2020 ◽

Vol 46 (1) ◽

Author(s):

Ingrid Anne Mandy Schierz ◽

Marcello Cimador ◽

Mario Giuffrè ◽

Claudia Maria Aiello ◽

Vincenzo Antona ◽

...

Keyword(s):

Cleft Palate ◽

Retinal Dystrophy ◽

Hirschsprung Disease ◽

Copy Number Variations ◽

Chromosomal Anomalies ◽

Single Mutation ◽

Loss Of Function ◽

Ileal Loop ◽

Total Colonic Aganglionosis ◽

Developmental Abnormalities

Abstract Background Hirschsprung disease, the most important congenital colonic dysmotility in children results from neural crest migration, differentiation, proliferation, or apoptosis defects where the rearranged during transfection (RET)-Protooncogene pathway has a central role. Although palatal and retinal anomalies in the context of chromosomopathies and some mono−/oligogenic syndromes are reported associated with Hirschsprung disease the role of inactivating RET mutations in these cases is not clarified. Case presentation We report on a dysmorphic newborn with cleft palate and palatal synechia, who showed intestinal obstruction after 24 h of life. Transient ileostomy and surgical biopsies were performed to diagnose aganglionosis of the colon and last ileal loop. No chromosomal anomalies or copy number variations were found. We identified a paternal heterozygous germline mutation c.1852 T > C, which results in the substitution of cysteine by arginine in the RET-receptor tyrosine kinase (p.C618R mutation). There was no family history of Hirschsprung disease, but the father underwent surgery for medullary thyroid carcinoma and was affected by retinal dystrophy. Conclusions The occurrence of Hirschsprung disease and carcinoma shows how a single mutation may be responsible for adverse effects: gain and loss of function of the same receptor. Furthermore, it would be interesting to study its dual role in face and retina embryology, and to extend targeted investigations of RET hotspots in these developmental abnormalities to facilitate counselling, follow-up, and tumor prevention. Complex surgical procedures and genetic testing as well as socio-economic impact are a challenge for familiar compliance.

Download Full-text

Clinical evaluation of a patient with single maxillary central incisor

Journal of Clinical Pediatric Dentistry ◽

10.17796/jcpd.26.2.k521j56563773367 ◽

2003 ◽

Vol 26 (2) ◽

pp. 181-186 ◽

Cited By ~ 1

Author(s):

Youko Kamasaki ◽

Satoshi Fukumoto ◽

Kazumi Kubota ◽

George Goto

Keyword(s):

Clinical Evaluation ◽

Cleft Lip ◽

Ectodermal Dysplasia ◽

Primary Dentition ◽

Developmental Anomaly ◽

Radiological Examination ◽

Central Incisor ◽

Maxillary Central Incisor ◽

Brain Anomalies ◽

Maxillary Lateral Incisor

Hypodontia in permanent dentition is the most common developmental anomaly and frequently found in the second premolar and maxillary lateral incisor. In the primary dentition, however, hypodontia appears to be less frequent, with the exception of cases such as ectodermal dysplasia and cleft lip and palate.We report a child with one primary maxillary central incisor at midline. The presence of a single permanent maxillary central incisor was also confirmed by radiological examination. Other intraoral abnormalities were detected including absence of upper labial frenulum and abnormal palatal structure, but no other facial or brain anomalies. Although the condition is exceedingly rare, a thorough examination for more serious anomalies should be conducted since it is suggested to be the mildest feature of holoprosencephaly.

Download Full-text

Goldberg-Shprintzen Syndrome Associated with a Novel Variant in the KIFBPGene

Molecular Syndromology ◽

10.1159/000514531 ◽

2021 ◽

pp. 1-4

Author(s):

Pelin Ozyavuz Cubuk

Keyword(s):

Developmental Delay ◽

Clinical Features ◽

Hirschsprung Disease ◽

Missense Mutations ◽

Dysmorphic Features ◽

Brain Anomalies ◽

Responsible Gene ◽

Novel Variant ◽

Exome Analysis ◽

Kinesin Family

Goldberg-Shprintzen syndrome (GOSHS) is characterized by microcephaly, developmental delay, dysmorphic features, Hirschsprung disease (HSCR), and brain anomalies. The kinesin family binding protein (KIFBP; MIM 60937) gene has been identified as the responsible gene of the syndrome. To date, 16 different biallelic KIFBP mutations have been identified in 34 patients with GOSHS. Even though most of these mutations are nonsense and frameshift, 3 missense mutations have also been described. Here, we report an 18-month-old patient with microcephaly, developmental delay, dysmorphic features and HSCR. Exome analysis was performed to clarify the etiology of the clinical features. A previously unreported homozygous c.1723delC (p.H575Ifs*19) variant was detected in the last exon 7 of KIFBP which led to GOSHS. According to our findings, we suggest that this mutation expands mutational databases and contributes to the understanding of the phenotypic features of the syndrome.

Download Full-text

Novel missense mutation of the TP63 gene in a newborn with Hay-Wells/Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) syndrome: clinical report and follow-up

Italian Journal of Pediatrics ◽

10.1186/s13052-021-01152-y ◽

2021 ◽

Vol 47 (1) ◽

Author(s):

Gregorio Serra ◽

Vincenzo Antona ◽

Mario Giuffré ◽

Federica Li Pomi ◽

Lucia Lo Scalzo ◽

...

Keyword(s):

Cleft Palate ◽

Missense Mutation ◽

Cleft Lip ◽

Ectodermal Dysplasia ◽

Clinical Signs ◽

Clinical Report ◽

Sequencing Analysis ◽

Genetic Syndrome ◽

Cleft Lip Palate

Abstract Introduction Ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, also known as Hay-Wells syndrome, is a rare genetic syndrome with ectodermal dysplasia. About 100 patients have been reported to date. It is associated to a heterozygous mutation of the tumor protein p63 (TP63) gene, located on chromosome 3q28. Typical clinical manifestations include: filiform ankyloblepharon adnatum (congenital adherence of the eyelids), ectodermal abnormalities (sparse and frizzy hair, skin defects, nail alterations, dental changes and hypohidrosis), and cleft lip/palate. Diagnostic suspicion is based on clinical signs and confirmed by genetic testing. Patient’s presentation We hereby report on a female newborn with erythroderma, thin lamellar desquamations, extensive skin erosions, sparse and wiry hair, filiform ankyloblepharon adnatum, agenesis of the lachrymal puncta, cleft palate and nail dysplasia. Her phenotype was compatible with AEC syndrome. Then, based on the clinical suspicion, sequencing analysis of the TP63 gene was performed, and revealed a de novo novel missense mutation. Eyelids adherence and cleft palate underwent surgical correction, while skin erosions were treated with topical antibiotics/antifungals and emollient/re-epithelizing creams. A surgical reconstruction is presently planned for the agenesis of the lachrymal puncta. The infant currently is 17 months of age and is included in a multidisciplinary follow-up. At present shows growth impairment and mild developmental delay, and typical signs of ectodermal dysplasia with small areas of dermatitis lesions on the scalp, without further abnormalities. Conclusions Our report underlines the relevance of an early and careful clinical evaluation in neonates with ankyloblefaron, facial dysmorphism, and signs of ectodermal dysplasia. In these cases, the suspicion of AEC syndrome must be promptly raised, and sequencing analysis of TP63 early performed as well. An individualized, multidisciplinary and long-term follow-up should be guaranteed to affected subjects and their families, also to identify associated morbidities and prevent possible serious complications and adverse outcomes.

Download Full-text

Il neonato con gli occhi socchiusi. La displasia ectodermica legata al gene TP63

Medico e Bambino pagine elettr ◽

10.53126/mebxxiv101 ◽

2021 ◽

Vol 24 (4) ◽

pp. 101-104

Author(s):

Mandy Schierz ◽

Giovanni Corsello

Keyword(s):

Genetic Analysis ◽

Cleft Palate ◽

Epidermolysis Bullosa ◽

Ectodermal Dysplasia ◽

Maxillary Hypoplasia ◽

Distal Phalange ◽

Target Sequencing ◽

Wells Syndrome ◽

Congenital Ichthyosiform Erythroderma ◽

Short Philtrum

An Italian female newborn presented with cleft palate, erythroderma, desquamations, skin erosions, ankyloblepharon filiforme adnatum, broad nasal root, short philtrum, thin vermillion border, maxillary hypoplasia, microstomia, microglossia, cupped ears, hypoplasia of the distal phalange of left index, widely spaced nipples and polythelia. The hallmarks of ankyloblepharon-ectodermal dysplasia-clefting syndrome (or Hay-Wells syndrome) as well as persistent scalp erosions led to exclude more frequent skin disorders like congenital ichthyosiform erythroderma or epidermolysis bullosa and to diagnose Hay-Wells syndrome by genetic analysis. Target sequencing of the tumour protein p63 (TP63) gene revealed a novel heterozygous missense mutation I576T in exon 13 (c. 1727T>C) in the sterile alpha motive domain. The paper reports the clinical features, differential diagnoses and prognosis in TP63-related ectodermal dysplasia.

Download Full-text