Neonatal diagnosis of circumferential skin creases.

BACKGROUND: Circumferential skin creases is a rare and heterogeneous disorder characterized by multiple and redundant skin folds, which can present as an isolated feature or in association with other phenotypic anomalies. Here, we report the case of a newborn who immediately captured our attention because of his phenotype. CASE: A male Caucasian infant was born at 39 weeks and 4 days of gestational age with an instrumental delivery, after a pregnancy characterized by threat of preterm birth at 32 weeks. Fetal ultrasounds were reported to be normal. The patient was the first child of non-consanguineous parents. Anthropometry at birth: weight 3.590 kg (0.57 SDS); length 53 cm (1.73 SDS); cranial circumference 35.5 cm (0.83 SDS). Clinical examination soon after birth revealed multiple, asymmetric and deep skin folds involving forearms, legs and lower eyelids (right > left). These folds seemed not to cause any physical discomfort. In addition, hypertrichosis, micrognathia, low-set ears and a thin, down-turned border of upper lip were observed. Cardio-respiratory, abdominal and neurological examination was unremarkable. There was no family history of similar appearance or other physical abnormalities. Given the clinical picture, an array-CGH was performed, which was normal. A genetic counseling was requested and Circumferential Skin Creases disorder was diagnosed based on the typical cutaneous involvement and, given the absence of other clinical signs, it was supposed a benign evolution, with skin folds tending to disappear over time. In addition, the baby's DNA was requested for a targeted genetic analysis, which resulted negative. CONCLUSIONS: This clinical case underlines the need of performing a detailed neonatal physical examination in order to realize a timely diagnostic approach. Our patient presented with multiple skin folds, facial dysmorphism but normal systemic and neurological examination. Anyways, since Circumferential Skin Creases may be associated with later neurological symptoms, a regular reevaluation is recommended.

First case of two supernumerary markers derived from chromosome 5 and chromosome 8.

BACKGROUND: Small supernumerary marker chromosomes (sSMC) are additional centric chromosome fragments too small to be identified by banding cytogenetics alone. A sSMC can originate from any chromosome and it is estimated that 70% of sSMC are de novo, while 30% are inherited. Cases of sSMC derived from chromosome 5 (sSMC5) are rare, accounting for1.4% of all reported sSMC cases. In these patients, the most common reported features are macrocephaly, dysmorphic facial features, heart defects, growth retardation, hypotonia, and intellectual disability. Also sSMC derived from chromosome 8 are very rare and the phenotype of patients with sSMC8 is very variable. Common clinical features of the patients include developmental delay, mental retardation, intellectual disability, hypotonia, hypospadias, attention deficit hyperactivity disorders (ADHD), skeletal anomalies, dysmorphic facial features, and renal dysplasia. To the best of our knowledge, in literature there are no cases with coexistence of sSMC5 and sSMC8, so we reviewed the literature to compare cases with SMC5 and those with SMC8 separately. This study is aimed to highlight the unique findings of a patient with the coexistence of sSMC5 and sSMC8. CASE PRESENTATION: We describe a female patient with two supernumerary markers derived from chromosome 5 (SMC5) and chromosome 8 (SMC8). The patient was born prematurely at 30 weeks with respiratory distress and bronchodysplasia. On physical examination she presented dysmorphic features, respiratory issues, congenital heart defect, developmental delay, and intellectual disability. The G-banded chromosome analysis on cultured lymphocytes revealed in all the analyzed cells a female karyotype with the presence of two supernumerary chromosomal markers and the array-CGH highlighted the region and the size of these two duplications. We also used the fluorescent in situ hybridization analysis (FISH) using painting of chromosomes 5 and 8 to confirm the origin of the two sSMC. So, the karyotype of the patient was: 48, XX, +mar1, +mar2. CONCLUSIONS: This is the first case with two markers: one from chromosome 5 and one from chromosome 8. Based on the data reported, we can affirm that the phenotype of our patient is probably caused mainly by the presence of the sSMC.

Array-CGH characterization of a de novo t(X;Y)(p22;q11) in a female with short stature and mental retardation.

We report the clinical and molecular investigations in a girl with 46,X,-X,+der(X)t(X;Y)(p22;q11) de novo karyotype who presented an intricate phenotype characterized by mental retardation and facial dysmorphisms in combination with short stature. The structure of the derivative X chromosome was studied using BAC array-CGH which disclosed the Xp22 breakpoint between the STS and the VCX3A gene and the presence of the Yq11.1qter chromosome. It is common that females with Xp;Yq translocations present only short stature and are normal in every other aspect. Thus, this would be the first case in which a girl with Xp;Yq translocation presents an unusual phenotype with intermediate male clinical features with Xp;Yq translocations. The risk of developing gonadoblastoma in females with Y chromosome material is also discussed and, to this effect, different explanations related to this apparent variation are also presented.

16q22.1 microdeletion detected by array-CGH in a family with mental retardation and lobular breast cancer.

We describe the case of a boy with psychomotor delay and dysmorphic features, with a germline 16q22.1 microdeletion identified by array-CGH. The deletion spans 0.24Mb and encompasses three genes (ZFP90, CDH3 and CDH1). The deletion has been demonstrated to be inherited from his mother who was affected by lobular breast cancer (LBC) without any other apparently phenotypic features. We suppose that the microdeletion, in particular ZFP90 which is cerebrally expressed, is causative for the boy's phenotype. Mental retardation in the affected boy can recognize several mechanisms such as variable expressivity, non-penetrance, multifactorial/polygenic inheritance, recessive inheritance, a second rearrangement event and epigenetics. Furthermore, we suggest that the deletion of the CDH1, a tumor suppressor gene, involved in hereditary diffuse gastric cancer (HDGC) and LBC predisposed the mother to the carcinoma.