ichthyosis

Sjogren-Larsson syndrome is a rare autosomal neurocutaneous disease, dermatologically manifested by congenital ichthyosis, associated with para/tetraplegia and developmental delay.

We present the case of two triplet patients, a girl, and a boy, 3 months old, admitted to the intensive care unit (ICU) due to respiratory distress, swallowing, and spasticity. The dermatological evaluation was requested due to the presence of generalized cutaneous xerosis, predominantly facial, in the girl and mild xerosis on the soles and face in the boy. The set of clinical signs and symptoms, together with the histopathological examination that revealed findings of ichthyosis, corroborated the diagnosis of this syndrome.

The importance of describing this case is mainly due to the rarity of the presentation, especially in the case of triplets in which two of the brothers have the syndrome and one does not, as well as an alert to physicians for the correct diagnosis and multidisciplinary and dermatological follow-up.

 Ichthyosis is an epidermal disruption that increases insensible water loss. Hypernatremic dehydration is a consequence of skin disruption. This study reviewed the treatment of hypernatremic dehydration in patients with ichthyosis comparing to patients with intact skin.

 We studied five neonates with hypernatremia, including three ichthyosis cases and two normal-skin neonates. This case-series study showed that the sodium correction rate is slower in infants with ichthyosis than in infants with normal skin. The first and second neonates needed less sodium than fluid intake than normal skin infants, although fluid requirement was lower in the third ichthyosis infant than in others due to less skin disruption in this infant.

 Fluid therapy in hypernatremic dehydration in ichthyosis patients is different from neonates with intact skin because of excessive insensible water loss in these patients. It may be needed to give more fluid and less sodium depending on the degree of skin disruption, which may not be determined by physical examination.

Cerebral dysgenesis, neuropathy, ichthyosis, and keratoderma (CEDNIK) syndrome is an autosomal recessive neuro-cutaneous disorder characterized by a collection of clinical manifestations, including microcephaly, cerebral dysgenesis, palmoplantar keratoderma, facial dysmorphism, and ichthyosis. The etiology of this condition has been proved to be a homozygous mutation in the SNAP29 gene, which has an essential role in dermatological and neurological manifestations of this syndrome. In this report, we present the first documented Iranian patient with CEDNIK syndrome. So far, only 14 cases of this condition have been reported globally.

Xp22.3 region is characterized by low frequency of interspersed repeats and low GC content. Several clinically important genes including ANOS1 (KAL1) reside in this region. This gene was first identified due to translocation between chromosomes X and Y in a patient with Kallmann syndrome.

A 20 year old male presented with complaints of delayed secondary sexual characteristics, impaired sense of smell, and poor scholastic performance. On examination, he had short stature (151 cm; <3rd centile). His sexual maturity corresponded to Tanner stage 3. Stretched penile length was 3.6 cm (<3rd centile). Right testis was undescended with low left testicular volume (12 ml). There was mild ichthyosis over abdomen and back. He had hyposmia, hoarse voice, and synkinesia. Investigations were suggestive of hypogonadotrophic hypogonadism. Karyotype revealed an extra chromosomal material on p arm of chromosome X (46,Xp+,Y). On cytogenetic microarray, deletion of 8.3 Mb on Xp22.33 region and duplication of 12.8 Mb on Yq11.22 region were identified. The breakpoint on X chromosome resulted in deletion of exons 7-14 of ANOS1 gene and complete STS, NLGN4X, ARSL (ARSE), SHOX, and VCX genes.

Patients diagnosed with Kallmann syndrome should receive careful clinical evaluation to detect presence of a contiguous gene syndrome.

Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is a rare autosomal recessive disorder mostly affecting the liver, kidney, skin, as well as central nervous and musculoskeletal systems. This multisystemic disease results from mutations in the vacuolar protein sorting 33B (VPS33B) or VPS33B- interacting protein, and apical-basolateral polarity regulator (VIPAR) genes. This is a lethal disorder from which few patients can survive at the first year of their life. This syndrome exhibits a wide range of phenotypes, such as ichthyosis, hypothyroidism, agenesis of the corpus callosum, and congenital cardiovascular anomalies.

Case report: 

Here, we present the case of a 32-day-old male neonate with respiratory distress admitted to Children's Medical Center Hospital in Tehran, Iran, in August 2019. He had ichthyosis, cholestasis with arthrogryposis as bilateral clubfeet, developmental dysplasia of the hip, and flexion contractures in upper limbs. During hospitalization, he received Shohl’s solution for metabolic acidosis, intravenous antibiotics, fat-soluble vitamins, and levothyroxine. Other  presentations in our case included  ichthyosis, failure to thrive, congenital heart disease, and hypothyroidism.

Timely diagnosis, supportive care and genetic counseling should be provided for better outcome.   Keywords:

Ichthyoses as epidermal genodermatoses are a large group of keratinization disorders that affect the entire integument, which is typically characterized by visible scaling and inflammation on the skin. Nowadays, in addition to clinical criteria, new molecular diagnostic methods, such as next-generation sequencing, can help to differentiate the subgroups of ichthyoses more precisely. These disorders are mostly classified based on clinical and histologic features and molecular markers. Inherited ichthyoses were divided into two groups: non-syndromic ichthyosis and syndromic ichthyosis. Non-syndromic ichthyosis is a group of various skin diseases with genetic and clinical heterogeneity. In this group, ichthyosis vulgaris and recessive X-linked ichthyosis are common and are often of delayed onset. Correct diagnosis of the molecular defects resulted from ichthyosis is useful for the prediction of the prognosis, genetic counseling (accurate risk assessment), prenatal diagnosis, and a better understanding of skin biology. However, the most essential and promising advantage of a precise molecular diagnosis is using gene therapy for its treatment, which may be considered as a subcategory of personalized medicine. This review is focused on the different aspects of non-syndromic ichthyoses pathophysiology.

Neu–Laxova syndrome (NLS) is an autosomal recessive disorder characterized by central nervous system anomalies, facial dysmorphic features, anomalies of limb and genitalia, intrauterine growth retardation, skin disorders, and other congenital abnormalities. In this article, we present a newborn infant who was born with facial dysmorphic features, flat nose, ichthyosis, rocker bottom feet, and fixed flexion contractures. We believe that these clinical findings in this patient are consistent with features of NLS.