Harlequin ichthyosis, prenatal diagnosis: the ultrasound recognition.

Harlequin ichthyosis (HI) is an extremely rare disease with a prevalence of less than 1/300 000 live newborns and no more than 100 cases reported worldwide. It corresponds to a genodermatoses autosomal recessive inheritance, typically, with postnatal recognition due to the complexity of prenatal diagnosis. Advances in prenatal genetic testing allow sequencing of the affected gene and confirmation of the diagnosis after recognition of ultrasound markers. The prenatal acknowledgement of the disease significantly marks the course of the pregnancy; considering the perinatal high risk and neonatal mortality, this entity can be classified as lethal. Taking into account the legislation of each country, the possibility of pregnancy termination should be considered as an acceptable option. We present a case of prenatally diagnosed HI in the first ultrasound evaluation by the Maternal Fetal Medicine unit at 29 weeks of gestation, in which after counselling to the parents, the interruption of the gestation was decided.

Two- and three-dimensional sonographic findings of harlequin ichthyosis: case report and literature review.

BACKGROUND: Harlequin ichthyosis (HI) is a rare skin disorder with extremely high lethality due to a mutation of the ABCA12 gene. Because of its rarity and the often-late onset, prenatal screening for HI is extremely difficult, and most pregnant women might easily miss the period for optimal examinations. OBJECTIVE: To summarize the sonographic features of HI for prenatal diagnostic purposes. METHODS: The authors describe a case of HI with no family history who was diagnosed by using prenatal ultrasound scanning. The sonographic features of HI and the clinical characteristics of pregnant women were summarized by searching relevant literature over nearly two decades. RESULTS: The unique sonographic presentations including peeling skin, clenched hands and clubfeet, ectropion, flat nose, fetal growth impairment, polyhydramnios and echogenic amniotic fluid may be primarily related to skin disorders in HI fetuses. The authors also identified a novel pathogenic ABCA12 gene mutation and explained the possible pathogenic mechanisms. STUDY LIMITATIONS: Caution should be exercised in summarizing disease characteristics because of the small number of cases, and the authors are faced with the possibility of incomplete case searching. CONCLUSIONS: HI has relatively unique sonographic features. Therefore, 2D-ultrasound combined with 3D-ultrasound may be an effective method for the prenatal diagnosis of HI. Moreover, a novel pathogenic ABCA12 gene mutation may provide important clues for future research on the etiology of HI. However, the authors consider that additional studies are needed to provide more evidence for prenatal diagnosis.

Prenatal diagnosis of a rare variant of harlequin ichthyosis with literature review.

BACKGROUND: Harlequin ichthyosis (HI) is a rare and severe genetic skin disorder that occurs within the developing foetus. Due to the extremely poor prognosis, prenatal diagnosis becomes very important, especially for foetuses with no family history. There are few reports on prenatal diagnosis in PubMed. CASE PRESENTATION: We report two cases of HI with no family history who were diagnosed by prenatal ultrasound. We searched for reports on the prenatal ultrasonic diagnosis of HI over nearly two decades and summarized the sonographic features of HI, the reasons for missed diagnoses and matters needing attention. A total of 10 articles of congenital harlequin ichthyosis diagnosed by prenatal ultrasound in PubMed were retrieved. There have been even fewer reports of late-trimester disease with no family history. Combining the two cases we reported with the literature review, we summarize the ultrasonic image characteristics of HI. CONCLUSION: HI can be easily detected by 2D ultrasound combined with 3D, but attention should be paid to a systematic examination in the third trimester of pregnancy according to the clinical characteristics of the disease.

Prenatal sonographic diagnosis of Harlequin ichthyosis.

Harlequin ichthyosis is the most severe form of autosomal recessive congenital ichthyoses. So far, there are only a few reports of prenatal diagnosis in the literature, as prenatal sonographic features are quite subtle. We report a case of prenatal diagnosis of Harlequin ichthyosis on third-trimester sonographic examination in a consanguineous couple with no history of the disease and describe its characteristic sonographic features.

Compound heterozygous missense mutations p.Leu207Pro and p.Tyr544Cys in TGM1 cause a severe form of lamellar ichthyosis.

TGM1 is the most common gene responsible for lamellar ichthyosis. Previous studies have suggested that patients with lamellar ichthyosis carrying two missense mutations in TGM1 show significantly less severe phenotypes than those with at least one truncating mutation in TGM1. Here, we report a patient with severe lamellar ichthyosis who was compound heterozygous for TGM1 missense mutations, including a novel one. A 22-year-old Japanese man presented with large, dark brown, plate-like scales on the extremities and small adherent scales on the face and trunk. His other clinical findings included ectropion, hair loss, hypohidrosis, hyperthermia in summer, palmoplantar keratoderma and constriction of the fingers. Dermoscopy revealed accentuated sulci cutis with numerous large keratotic plugs in the cristae cutis. Histologically, orthohyperkeratosis and mild acanthosis were noted. Electron microscopy showed reduced cornified envelope thickness and numerous lipid droplets in the stratum corneum. Mutation analysis revealed the patient to be compound heterozygous for missense mutations, c.620T>C (p.Leu207Pro) and c.1631A>G (p.Tyr544Cys), in TGM1. Furthermore, we showed that TGM1 enzymatic activity was largely absent in his epidermis. These findings led us to diagnose him as having lamellar ichthyosis. This study has two important notions. First, even two missense mutations in TGM1 can cause severe lamellar ichthyosis. Second, this is the first report of dermoscopic findings of lamellar ichthyosis, implicating the obstruction of sweat glands by keratotic plugs in the pathogenesis of hypohidrosis in the disease. In conclusion, this study provides further insights into genotype-phenotype correlations and pathogenesis in lamellar ichthyosis.

Prenatal diagnose of a fetus with Harlequin ichthyosis in a Chinese family.

OBJECTIVE: Harlequin ichthyosis (HI) was the most severe form of ichthyoses, which leaded to neonatal death in 50% of cases. It was the result of mutations in ABCA12 gene. With the development of ultrasound skills and genetic analysis, HI could be prenatal diagnosed. CASE REPORT: Here, we reported a case of HI, which was prenatal diagnosed by ultrasound examination and genetic analysis. The fetus was found that severe ectropion, eclabium, flattened nose, and rudimentary ears by ultrasound at 20 weeks gestation. A molecular genetic analysis was performed and revealed two mutations in the ABCA12 gene. One of two mutations were not reported in the past. The fetus was terminated. CONCLUSION: HI was associated with the poor prognosis of HI neonates. Prenatal ultrasound and genetic analysis were important for prenatal diagnosis of HI and were helpful to give sufficient prenatal counsels for the family with HI baby.

Prenatal diagnosis of Harlequin ichthyosis presenting as distal arthrogryposis using three-dimensional ultrasound.

We describe a case of Harlequin Icthyosis where the main 2D and 3D ultrasound findings were digital contractures as opposed to the more commonly described severe facial dysmorphisms. A prenatal finding of distal arthrogryposis can therefore include harlequin icthyosis as a differential diagnosis, where 3D ultrasound may then disclose the facial features more commonly associated with the condition.

Harlequin ichthyosis: report of one case.

Harlequin ichthyosis (HI) is the most devastating form of skin disorder, which is inherited as autosomal recessive trait related to consanguineous marriage. Although prenatal examination has become scheduled and convenient throughout Taiwan, an unexpected case of HI in a male premature infant born at 32 weeks of gestation was presented. The parents were healthy, neither relatives nor having history of congenital abnormality. We report our management and the massive impact left on both parents. We believe this is an extremely rare case in Taiwan.

Harlequin ichthyosis--difficulties in prenatal diagnosis.

Ichthyoses belong to the group of genodermatoses, characterized by hyperkeratosis and desquamation of the epidermis. Clinical manifestation is heterogeneous and depends on the type of the disease. Harlequin foetus is the most severe form of congenital ichtyosis, inherited as an autosomal recessive trait. The disfunction of the epidermis begins prenatally. Neonates are often born prematurely, in severe condition. At present better care and treatment prolong the length and quality of children's life. We report a case of harlequin ichthyosis. Parents were healthy and there was no history of ichthyosis or other congenital anomalies in the family. Sonography at the 26th week of gestation revealed anomalies of the fetal face; however, the diagnosis of harlequin ichthyosis was not established prenatally. The male child was born alive at the 37th week of the third pregnancy, with birth weight of 2900 g. Typical features of harlequin ichthyosis were present at birth. Intensive neonatological care was necessary. The child survived and at the time of the report was 6 months old and in good condition.

Short foot length: a diagnostic pointer for harlequin ichthyosis.

OBJECTIVE: Among the fetal skin disorders, harlequin ichthyosis is the one that has specific sonographic features in the antenatal period. A few cases of antenatal diagnosis of harlequin ichthyosis with typical facial features of ectropion and eclabium have been described. The manifestation of the phenotype is usually in the third trimester. Fetal skin biopsy can be done in the late second trimester for diagnosing fetal skin disorders. We aimed to see whether a short foot length could be a pointer for the diagnosis of harlequin ichthyosis in the second trimester before the full phenotypic manifestation, which is usually seen in the third trimester. METHODS: We report 3 cases of harlequin ichthyosis, 2 of them diagnosed in the third trimester with abnormal facial features and another second-trimester sonographic diagnosis based on short foot length, without eclabium and ectropion. RESULTS: In all 3 cases, the foot length was considerably smaller than the femur length, especially in the third case, in which the foot length was smaller than the femur length before the manifestation of the typical features of harlequin ichthyosis. CONCLUSIONS: Fetal foot length may be an important and probably the first marker seen in the second trimester for the diagnosis of harlequin ichthyosis.

Three-dimensional sonographic findings in congenital (harlequin) ichthyosis.

Harlequin ichthyosis is a lethal autosomal recessive disorder characterized by an extremely thickened keratin layer of skin, flattened ears, and diffuse platelike scales. Prenatal sonographic diagnosis has been described, with findings of a persistently open mouth, echogenic amniotic fluid, and fixed flexion of the extremities. Here we describe a case of harlequin ichthyosis in which the syndromic features were shown best on three-dimensional (3D) and four-dimensional (4D) real-time sonography.

Harlequin fetus: three-dimensional sonographic findings and new diagnostic approach.

Congenital ichthyosis, otherwise known as harlequin fetus, is a severe, generally lethal, anomaly. Prenatal diagnosis is usually possible in families at risk but requires invasive fetoscopy for skin biopsy. The application of three-dimensional ultrasound enables a greatly improved analysis of the facial morphology and thus provides an important contribution to prenatal diagnosis. Although such three-dimensional diagnostic procedures are performed in specialized centers, sonographers should be aware of the signs observed at routine two-dimensional ultrasound examination in order to ensure appropriate referral for diagnosis. We describe two consecutive pregnancies of the same parents in which two- and three-dimensional ultrasound were used in the prenatal diagnosis of harlequin fetus.