| Disorder |
Inheritance / Genetic Basis |
UK Frequency (Approx) |
Worldwide / Population Notes |
Typical Clinical Clues |
Diagnosis & Key UK Actions |
| ๐ซ Cystic Fibrosis (CF) |
Autosomal recessive; CFTR variants โ defective chloride channel |
~1 in 2,500 births |
Higher in Northern European ancestry |
Recurrent chest infections, bronchiectasis, steatorrhoea, poor growth, male infertility |
Newborn blood spot โ sweat chloride (>60 mmol/L) + genetics; MDT care; airway clearance; pancreatic enzymes; CFTR modulators where eligible |
| ๐ฉธ Sickle Cell Disease |
Autosomal recessive; HBB (HbS polymerisation) |
~1 in 2,800 births |
Common in malaria-endemic ancestry (carrier advantage) |
Vaso-occlusive pain, haemolytic anaemia, infections, stroke, acute chest syndrome |
Newborn screening; penicillin + vaccines; hydroxycarbamide; stroke prevention transfusion programmes; specialist haemoglobinopathy MDT |
| ๐งฌ Thalassaemia (ฮฑ/ฮฒ) |
Autosomal recessive; reduced globin synthesis |
Lower birth prevalence than carrier rate |
Very high carrier frequency in Mediterranean, Middle East, South/SE Asia |
Microcytosis disproportionate to anaemia, family history, transfusion dependence (major) |
FBC + film; Hb electrophoresis/HPLC; antenatal screening; transfusion + iron chelation (major) |
| ๐ถ Down Syndrome (Trisomy 21) |
Chromosomal aneuploidy (non-disjunction) |
~1 in 854 live births |
Varies with maternal age & screening uptake |
Hypotonia, AVSD, thyroid disease, learning disability |
Karyotype; neonatal echo; hearing screen; structured lifelong surveillance (thyroid, OSA, vision) |
| ๐ง Fragile X Syndrome |
X-linked; FMR1 CGG repeat expansion |
~1 in 4,000 males |
Leading inherited cause of learning disability |
Learning disability, autism traits, anxiety; macroorchidism post-puberty |
Genetic repeat sizing; family cascade testing; neurodevelopmental MDT support |
| ๐ Duchenne Muscular Dystrophy |
X-linked; DMD (dystrophin absence) |
~1 in 3,500โ5,000 male births |
~1/3 de novo mutations |
Proximal weakness, Gowersโ sign, calf pseudohypertrophy, very high CK |
Genetic confirmation; steroids; physio; respiratory & cardiac surveillance; neuromuscular MDT |
| ๐ Haemophilia A / B |
X-linked; Factor VIII / IX deficiency |
A: ~1 in 5,000 males
B: ~1 in 25,000โ30,000 |
Worldwide; outcomes depend on access to factor replacement |
Haemarthroses, muscle bleeds, prolonged bleeding after procedures |
Isolated prolonged APTT โ factor assay; prophylactic factor or emicizumab (A); haemophilia centre care |
| ๐งด Neurofibromatosis Type 1 |
Autosomal dominant; NF1 tumour suppressor gene |
~1 in 2,500โ3,000 |
~50% de novo mutations |
Cafรฉ-au-lait macules, axillary freckling, neurofibromas, optic glioma |
Clinical criteria; annual surveillance; vision & BP monitoring; education re malignant change |
| ๐ซ Marfan Syndrome |
Autosomal dominant; FBN1 (connective tissue defect) |
~1 in 3,000โ5,000 |
Worldwide; mortality linked to aortic dissection |
Tall habitus, lens subluxation, aortic root dilatation |
Ghent criteria; echo surveillance; beta-blocker/ARB; prophylactic aortic surgery; family screening |
| ๐๏ธ BRCA1/2-Related Cancer |
Autosomal dominant cancer predisposition |
~1 in 200โ400 carriers |
Higher in Ashkenazi Jewish ancestry (~1 in 40) |
Early breast/ovarian cancer, strong family clustering |
Genetics referral; enhanced MRI screening; chemoprevention; risk-reducing surgery; cascade testing |
