Smith-Lemli-Opitz syndrome
Classification according to ICD-10 | |
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Q87.1 | Congenital malformation syndromes that are predominantly associated with short stature - Smith-Lemli-Opitz syndrome |
ICD-10 online (WHO version 2019) |
The Smith-Lemli-Opitz syndrome ( SLO syndrome , SLOS ) is a congenital autosomal recessive inheritable malformation syndrome based on a gene mutation . Typical is a metabolic disorder of cholesterol - biosynthesis , in which a decreased activity of the 7-dehydrocholesterol reductase (DHCR7) is composed, which results in a lack of cholesterol. The SLOS is also known under the synonym RSH syndrome or RSH syndrome (Opitz) . The acronym RSH refers to the names of the first three patients described with this syndrome.
frequency
The prevalence of the syndrome in Europe is around 1: 60,000 to 1: 10,000; in Asia and Africa, for example, it is even less common. Since the syndrome was first described scientifically in 1964 by geneticists David W. Smith , Luc Lemli and John Marius Opitz , more than 300 cases have been published. The diagnosis is mainly made in boys, probably because a lighter manifestation of symptoms in girls makes diagnosis more difficult.
Cause and inheritance
The cause of Smith-Lemli-Opitz syndrome was discovered in 1998 when mutations (more than 70 are now known) of the 7-sterol reductase gene were discovered on chromosome 11q13.4 : Steven Tint and his colleagues found that the The body's own production of cholesterol does not work in people with the syndrome because the conversion of the cholesterol precursor 7-dehydrocholesterol into cholesterol is not possible due to an enzyme defect . This leads to an excess of 7-dehydrocholesterol (7-DHC) and a deficit of cholesterol. The type of mutation influences the severity of the symptoms.
The inheritance of the syndrome is autosomal recessive ( locus 11q13.4 / DHCR7), i. H. the parents carry the faulty gene and both pass it on to their child. This combination of defective parental genes leads to the development of Smith-Lemli-Opitz syndrome in children. The probability that parents who have already had a child with the syndrome will have another affected child in a subsequent pregnancy is 25%.
diagnosis
During ultrasound examinations as part of prenatal diagnosis , typical physical features such as a stunted growth, an unusually small head, heart defects and / or lack of a kidney are often noticed. During an amniocentesis (amniotic fluid test), a mutation analysis can be carried out (determination of 7-dehydrosterol and chorionic biopsy). Experienced diagnosticians can also detect so-called pseudo- hermaphroditism prenatally with type II of the syndrome : In terms of the external genitals , the children are female, while their karyotype is male. Unphysiological steroids are present in the urine of the pregnant woman and a low plasma estriol level can also be detected. After a confirmed prenatal diagnosis, the parents can choose to have the pregnancy terminated for medical reasons or to prepare for the birth of the child (e.g. choice of clinic).
After the birth, the children may fall. a. by a characteristic face shape on and by special positions of the extremities; other symptoms lead to a suspected diagnosis, which is followed by genetic testing for diagnosis.
The ICD-10 code Q87.1 ( congenital malformation syndromes , which are predominantly associated with short stature ) is indicated in the diagnosis of Smith-Lemli-Opitz syndrome.
Differential diagnostics
Differential diagnostics are to be distinguished from type I:
- Fetal alcohol syndrome
- Pallister Hall Syndrome
- McKusick-Kaufman syndrome
- Cornelia de Lange Syndrome
- Patau syndrome (trisomy 13)
- ATR-X syndrome
and with type II too
- C syndrome
- Zellweger Syndrome
- Hydroletalus Syndrome
- Oro-facio-digital syndrome
- Holoprosencephaly-Polydactyly Syndrome
- Mowat-Wilson syndrome
- Meckel syndrome .
Symptoms
The symptoms are variable and their severity different. Described both before or soon after birth fatal ( lethal ) running characteristics associated with many physical malformations ( Smith-Lemli-Opitz syndrome type II ) and mild forms with just a few features and good prognosis of life expectancy. The lower the cholesterol value, the more severe the symptoms of the syndrome. The following symptoms are considered typical characteristics, although not all children have all characteristics to the same extent:
- Heart defects (often Fallot's tetralogy , atrial septal defect , ventricular septal defect , open ductus arteriosus )
- Microcephaly (a comparatively small head) with ears comparatively low
- drooping eyelids ( ptosis / blepharoptosis / "heavy eyes"), epicanthus medialis (additional crescent-shaped skin folds at the inner corners of the eyes)
- upward (anteverted) nostrils, broad nasal bridge
- irregular tooth spacing
- Cataract (cataracts), glaucoma (green star)
- Syndactyly 2/3 of the toes , postaxial polydactyly (additional fingers and / or toes, usually in the form of a hexadactyly ), short thumbs, four-finger furrow
- Hand and foot misalignments
- Corpus callosum or hypoplasia, disorders of Gyrierung ( Polymicrogyria )
- Hypoplasia (underdevelopment) of the frontal lobe and cerebellum
- Holoprosencephaly , hydrocephaly
- Microretrognathia (the lower jaw is smaller than usual and shifted backwards), cleft palate
- Undescended testicles , hypospadias (urethra opens on the underside of the penis), Urethrastenose
- partly female genitalia in children with a male chromosome set
- Renal agenesis (lack of a kidney ), cyst kidney , hydronephrosis (urinary stasis), adrenal insufficiency , duplication of the urethra
- Narrowing of the stomach outlet ( pyloric stenosis )
- Hirschsprung's disease
- Liver disease
- Underdevelopment of the lungs ( pulmonary hypoplasia ), malformation of the lung lobe
- Behavioral disorders: restlessness, screaming fits, sleep disorders, self- harming behavior , autistic traits (disruption of the ability to make contact, weighing the body , stereotypical hand movements), problems with feeding (it may be necessary to insert a feeding tube )
- Short stature
- sometimes the development of spoken language and the development of motor skills (learning to walk) fail to appear
- Physical disabilities and cognitive disabilities of varying degrees of severity
- Sensitivity to light ( photosensitivity )
development
The life expectancy is primarily dependent upon the concentration of cholesterol in the organism , and the severity and treatability of organ malformation (particularly in the region of the heart and the kidneys ). While most babies with extremely low cholesterol levels and / or the most severe malformations die in the course of the first few months after birth , the life expectancy of less severely impaired children is not reduced with good medical and social care. However, their development is significantly delayed, both in the cognitive and in the motor area. Lifelong disabilities in these areas are to be expected; an independent lifestyle is usually not possible.
therapy
The Smith-Lemli-Opitz syndrome cannot be cured. However, knowing about the disturbance of the cholesterol metabolism enables appropriate treatment to compensate for the deficiency by giving cholesterol. In addition, many malformations of the organs can be corrected surgically and other symptoms (e.g. visual difficulties ) can also be treated. Since most children nutritional problems (like sucking and swallowing difficulties , gastroesophageal reflux , impaired stomach - intestine - peristalsis , frequent vomiting ) is sometimes the use of a feeding tube needed and the food intake to ensure. The problematic eating behavior often changes as the cholesterol level is balanced; and behavioral abnormalities may improve characterized.
Web links
- Smith-Lemli-Opitz syndrome. In: Online Mendelian Inheritance in Man . (English).
Individual evidence
- ^ Smith-Lemli-Opitz syndrome. In: Online Mendelian Inheritance in Man . (English)