• Dandy–Walker-Malformation
• Dandy–Walker-Syndrome
• fourth ventricle

• MR/L010305/1 Medical Research Council
• School of Psychology, Cardiff University

• Brain malformations
• FLNA
• Genetics
• Malformations of cortical development
• Periventricular nodular heterotopia
• Subcortical band heterotopia

X‐linked ichthyosis (XLI) is the second most common type of ichthyosis, which is characterized by wide and symmetric distribution of adherent, dry, and polygonal scales on the skin. Steroid sulfatase (STS) gene, which is located at chromosome Xp22.31, has been identified as the pathogenic gene of XLI.

In this study, chromosome karyotype analysis, bacterial artificial chromosomes‐on‐Beads™ (BoBs) assay, fluorescence in situ hybridization (FISH), and single nucleotide polymorphism array (SNP‐array) were employed for the prenatal diagnoses in three pregnant women with high‐risk serological screening results and a pregnant woman with mental retardation.

STS deletion was identified at chromosome Xp22.31 in all four fetuses. Postnatal follow‐up confirmed the diagnosis of ichthyosis in two male fetuses and revealed normal dermatological manifestations in other two female fetuses carrying ichthyosis.

The results of the present study demonstrate that a combination of karyotypying, prenatal BoBs, FISH, and SNP‐array may avoid the missed detection of common microdeletions and ensure the accuracy of the detection results, which provides a feasible tool for the reliable etiological diagnosis and better genetic counseling of XLI.

• STS gene
• X-linked ichthyosis
• epidermal barrier function
• prenatal diagnosis
• steroid sulfatase deficiency

• copy-number
• developmental
• epilepsy and seizures
• genome-wide

• Argentina
• Cholinergic Neurons
• DNA Copy Number Variations
• Epilepsy, Rolandic/genetics
• Female
• Genetic Predisposition to Disease
• Genetic Testing
• Humans
• India
• Italy
• Male
• Synapses
• United States

• Wellcome Trust
• MR/K006584/1 Medical Research Council
• European Union Grant
• Eli Lilly and Company
• European Union Marie Curie International Reintegration Award of the Seventh Framework Programme
• Charles Sykes Epilepsy Research Trust
• Ali Paris Fund for Epilepsy Research
• Waterloo Foundation
• NIHR Specialist Biomedical Research Centre for Mental Health of South London and Maudsley NHS Foundation Trust

Short arm deletions of the X-chromosome are challenging issues for genetic counseling due to their low penetrance in population. Female carriers of these deletions have milder phenotype than male ones, considering the intellectual ability and social skills, probably because of the X-chromosome inactivation phenomenon.

A female patient with a 10Mb distal Xp deletion and an Xq duplication, showing mild intellectual disability, is described in this report. While the deletion arose from a maternal pericentric inversion, the duplication was directly transmitted from the mother who is phenotypically normal.

This report underlines the usefulness of molecular cytogenetic technics in postnatal diagnosis.

• Array CGH
• Classical cytogenetics
• Genetic counseling
• Pericentric inversion
• Xp deletion
• Xq duplication

• Autism
• Brain development
• Neurogenetics
• Neuroimaging
• Sex differences

X-linked ichthyosis is a dermatological condition caused by deficiency for the enzyme steroid sulfatase. Previously, X-linked ichthyosis/steroid sulfatase deficiency has been associated with developmental and neurological phenotypes. Here, we show for the first time, that X-linked ichthyosis may be comorbid with an additional psychiatric phenotype (psychosis).

We report the case of an 11-year-old Saudi Arabian boy with X-linked ichthyosis associated with psychosis, mental retardation, autism spectrum disorder, inattentive attention deficit hyperactivity disorder, and epilepsy. Genetic analysis revealed a 1.68 Mb deletion encompassing STS in 95% of cells while biochemical analysis revealed correspondingly low steroid sulfatase activity consistent with a diagnosis of X-linked ichthyosis. The psychotic symptoms could be reasonably well controlled by administration of an atypical antipsychotic.

This report describes a case of comorbid X-linked ichthyosis and psychosis (most closely corresponding to early-onset schizophrenia) for the first time, and suggests that deficiency for steroid sulfatase and contiguous genes may increase vulnerability to psychosis as well as other psychological disorders.

• Attention deficit hyperactivity disorder
• Autism spectrum disorder
• Case report
• Epilepsy
• Psychosis
• Steroid sulfatase
• X-linked ichthyosis

• Comorbidity
• growth and development
• malformations of cortical development
• nervous system malformations

X-linked ichthyosis (XLI) is an X-linked recessive skin disorder generally restricted to males, which arises from mutations in the steroid sulfatase (STS) gene located on Xp22.3. Crigler-Najjar syndrome (CN-I) is a rare autosomal recessive disease caused by the homozygous or compound heterozygous mutations in the UPD-glucuronosyltransferase 1 family, polypeptide A1 (UGT1A1) gene on chromosome 2q37. A male patient was referred to the Department of Medical Genetics with of severe icterus and ichthyosis. The patient and his family members underwent genetic tests related to XLI and CN-I. Quantitative polymerase chain reaction on genomic DNA was performed to determine the gene copy number, while single nucleotide polymorphism array analysis was conducted to identify deletion mutations. Family pedigree analysis showed that the patient and his two cousins were all affected by ichthyosis, which was in accordance with the inheritance pattern of an X-linked recessive disease. In addition, the patient's serum bilirubin concentration (>340 mmol/l) was markedly greater than the normal level. The patient presented with kernicterus and phenobarbital treatment was ineffective. The clinical diagnosis of XLI was confirmed molecularly by laboratory evidence of a maternal 1.61 M deletion (including the STS gene) on ChrXp22.31. Coincidentally, the male patient was also confirmed to carry a rare maternal inherited microdeletion (374 Kb) comprising the entire UGT1A1 gene combined with a paternal UGT1A1 mutation (c.1253delT), a causative event of CN-I. To the best of our knowledge, this study reported for the first time the comorbidity of XLI and CN-I in a male patient. The results suggested that co-occurrence of these two recessive diseases in a patient may be incidental.

• X chromosome
• genodermatology
• mosaicism
• multidisciplinary
• review

The enzyme steroid sulfatase (STS) desulfates a variety of steroid compounds thereby altering their activity. STS is expressed in the skin, and its deficiency in this tissue has been linked to the dermatological condition X-linked ichthyosis. STS is also highly expressed in the developing and adult human brain, and in a variety of steroidogenic organs (including the placenta and gonads); therefore it has the potential to influence brain development and function directly and/or indirectly (through influencing the hormonal milieu). In this review, we first discuss evidence from human and animal model studies suggesting that STS deficiency might predispose to neurobehavioural abnormalities and certain psychiatric disorders. We subsequently discuss potential mechanisms that may underlie these vulnerabilities. The data described herein have potential implications for understanding the complete spectrum of clinical phenotypes associated with X-linked ichthyosis, and may indicate novel pathogenic mechanisms underlying psychological dysfunction in developmental disorders such as attention deficit hyperactivity disorder and Turner syndrome.

• Acetylcholine
• Aggression
• Attention
• Attention deficit hyperactivity disorder
• Dehydroepiandrosterone sulfate
• Impulsivity
• Hippocampus
• Postpartum psychosis
• Serotonin

• Female
• Humans
• Male
• Mental Retardation, X-Linked
• Mosaicism
• Sex Chromosome Aberrations
• Sex Chromosomes
• X Chromosome Inactivation

• aldh3a1
• fatty aldehyde
• ichthyosis
• mutation
• slc47a1
• ulk2

• Aldehyde Oxidoreductases/genetics
• Aldehyde Oxidoreductases/metabolism
• Base Sequence
• Chromosomes, Human, Pair 17/genetics
• Comparative Genomic Hybridization
• DNA Primers/genetics
• Female
• Gene Deletion
• Genotype
• Humans
• In Situ Hybridization, Fluorescence
• Infant
• Microarray Analysis
• Molecular Sequence Data
• Mutation, Missense/genetics
• Pedigree
• Polymerase Chain Reaction
• Sequence Analysis, DNA
• Sjogren-Larsson Syndrome/genetics
• Sjogren-Larsson Syndrome/pathology
• Young Adult

• R01 MH092902 NIMH NIH HHS
• R01 AR044552-14 NIAMS NIH HHS
• AR044552 NIAMS NIH HHS
• R01 AR044552-15 NIAMS NIH HHS
• R01 AR044552-13 NIAMS NIH HHS
• R01 AR044552 NIAMS NIH HHS

• Adult
• Basal Cell Nevus Syndrome/complications
• Basal Cell Nevus Syndrome/genetics
• Carcinoma, Basal Cell/diagnosis
• Carcinoma, Basal Cell/surgery
• Chromosomes, Human, Pair 9/genetics
• Humans
• Male
• Skin Neoplasms/diagnosis
• Skin Neoplasms/surgery