For full rundown on all syndromes, go to OMIM, where you can search by clinical feature. There are no images unfortunately, but there is a small collection at Genetics Image Catalogue. For definitions of genetic terms eg anticipation, go to Geneclinics.org where there is an illustrated glossary. Conditions affecting only 1 system eg Osteogenesis imperfecta can be found under system.
Arguably owned jointly by all family members! But linkage studies (where patterns of DNA through families studied) are done rarely now cf specific gene tests. Although there may be a moral imperative for information to be shared, as in STIs, there is rarely an urgent need, and moral does not equate to legal obligation.
Trisomy 18, occurs 1 in 8000 births.
Trisomy 13, occurs 1 in 14000 births.
Similar ears, worse eyes, plus cleft.
The syndrome of chromosome 22q11 microdeletion includes congenital heart disease, cleft palate or velopharyngeal insufficiency, hypocalcaemia, renal anomalies, recurrent coughs and colds, learning difficulties, speech delay, and behaviour problems. See Immunology.
The thrombocytopenia-absent radius (TAR) syndrome is characterised by both thumbs being present! (absent thumbs suggest other syndromes). Thrombocytopenia usually presents in early infancy but may be transient and tends to remit in later childhood. The main conditions which might be mistaken for TAR syndrome are Holt-Oram syndrome, Roberts syndrome, Fanconi anaemia, thalidomide embryopathy.
The thumbs, though present, are always either hypoplastic or proximally placed. Most have relatively mild arm malformation with normal shoulder girdle and normal strength. Others have more marked limb shortening with underdevelopment of the ulna, humerus, shoulder girdle and reduced strength or phocomelia. Lower limb abnormalities are common.
Cow’s milk intolerance affects almost half and is severe, even requiring TPN! Other associated abnormalities include renal, cardiac and facial anomalies. Chromosome analysis is unhelpful. The pattern of inheritance remains unclear but there is definitely a recurrence risk.
Chromosome 15, paternal deletion else mat uniparental disomy. Thick secretions ("string sign"). Normal hands/feet as baby (small when older). Almond eyes, micropenis, poor feeding, hypotonia. Later hyperphagia and obesity, mental retardation.
Prader Willi parents support group
The lysosome is an organelle containing enzymes. Produced in the Golgi apparatus, fuse to vacuoles to disperse enzymes, important in autolysis (hence "suicide bags"). Many examples:
Fragile X mental retardation syndrome is a major cause of learning disability associated with a trinucleotide repeat expansion. Called Fragile X because under certain growth conditions, the chromosome has a tendency to break at this site (called the FRAXA site, to differentiate from other fragile sites on the X chromosome also associated with mental retardation, FRAXE and FRAXF).
Clinical features:
The problem is usually an expansion of trinucleotide repeat sequences at Xq27.3, affecting the FMR1 gene with (CGG)n repeat expansion of more than 200 repeats. Although the full syndrome is seen in males, females can be mildly affected, as can male carriers (about 50% show clinical features). The FMR1 genes produces the FMRP protein, which interacts with the mGluR5 glutamate receptor. Absence leads to long term depression in brain synapses. Consider it a spectrum of clinical manifestations seen with different numbers of trinucleotide repeats. The expansion anticipates in females carriers, not in males.
Fragile X tremor/ataxia syndrome is seen with premutations, ie 55 to 200 repeats. Presents as late as the sixth decade in men, with progressive intention tremor, Parkinsonism, cognitive decline. In women, associated with premature ovarian failure.
Differential diagnosis is precocious puberty. Diagnosis: urine for trimethylamines. Secondary form exists, due to bacterial overgrowth: treat with metronidazole.
VATER is a mnemonically useful acronym for
Nearly all cases have been sporadic, with no recognized teratogen or chromosomal abnormality. More common in infants of diabetic mothers. The VATER association was later expanded to the VACTERL association. VACTERL is an acronym for
Diagnosis made if 3/7 defects are present.
CHARGE stands for:
Note that none of the letters used in the acronym are the same as used in VACTERL.
Facial palsy, cleft palate, and dysphagia are commonly associated.
The term CHARGE should be restricted to infants with multiple malformations and choanal atresia and/or coloboma, combined with other cardinal malformations (heart, ear, and genital), for a total of at least 3 cardinal malformations; growth retardation, especially low birth weight, should not be used in the definition.
Mostly isolated, mutation in CHD7 gene (associated with increasing paternal age).
45XO but mosaics occur.
Trisomy 21. Features are:
Differential is Zellwegers. Rapid diagnosis is now done by PCR (previously FISH).
In the antenatal/neonatal period, particular problems include:
Complications include:
See Practical for breaking the diagnosis.
Downs syndrome medical Interest Group for doctors, for parents.
Cerebrohepatorenal syndrome. Omim #214100.
Diagnosis is by reduced DHAP-AT activity. Clues are high iron, high very long chain fatty acids, and low plasmalogens (peroxisome product).
Death usually in first year.
Homocystinuria - high arched palate, malar rash, lens dislocation by 8yr (preventable), osteoporosis, thromboembolism.
Pompes - lysosymal so no hypoglycaemia, muscle weakness, cardiomyopathy with large QRS, recurrent RTIs. No bone involvement. Late onset - proximal muscle weakness @30yrs! Gene therapy research has been knocked back after death in US of patient due to virus agent.
Actually 3 different gene defects possible, most commonly Galactose-1-Phosphate uridyl transferase deficiency (GALT, or Gal-1-PUT). The others have different phenotypes.
Presents in the newborn period after initiation of milk feeding, most commonly with jaundice, which can be unconjugated in first week but becomes conjugated thereafter. The other features listed below are seen in only a minority:
Lab findings include hypoglycaemia, deranged LFTs, coagulopathy, metabolic acidosis, abnormal urine aminoacid excretion. Urine for reducing substances is not sensitive or specific. The definitive test is RBC Gal-1-PUT activity, but if a transfusion has been given alternatives are genotyping or testing the parents for carrier status.
Management is by diet. Nonetheless, neuropsych problems usually develop in adolescence and ovarian failure often occurs. Some debate about whether galactose can be tolerated from age 2-3yr.
Transient hyperammonaemia seen in the under 32/40s - responds to bolus arginine.
Treatment:
Includes Mitochondrial myopathies eg MELAS & MERFF, Lebers optic atrophy, Leigh disease. Fatty acid oxidation disorders, plus lysosomal storage disorders (see above).
Fatty acid oxidation defects. 2 types of CPT -
Treatment: avoid fasting and/or exercise, a low-fat diet enriched with medium chain triglycerides and carnitine.
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