Rare syndromes — alphabetical A–Z 🧬

For education and revision only. Check current NICE/BNF, specialist guidance and local NHS policy before clinical use. Newly added V19 material has not received independent clinical sign-off.

Rare syndromes — one page, alphabetical reference. This is a selected clinical and examination-oriented set of rare genetic and multisystem syndromes, not a complete catalogue of all rare diseases. Use the browser find function or search within this article. The prominence of a disorder here does not indicate its actual population prevalence.

How to use this page

• Look for age at onset, inheritance pattern, dysmorphism, cardiac defects, neurological signs, skin and renal findings together; do not diagnose a syndrome from one feature.
• Stabilise the immediate problem first (airway compromise, seizures, arrhythmia, bleeding, sepsis, metabolic decompensation) and use local specialist pathways.
• Use clinical genetics/genomic laboratory advice for appropriate molecular tests; negative broad screening does not exclude repeat-expansion, imprinting or mosaic disorders.
• Common/high-yield syndromes are kept separate and linked below; historical emergency syndrome pages remain separate for patient safety.

A

• Aicardi syndrome — Usually affects girls; infantile spasms, agenesis of corpus callosum and chorioretinal lacunae. Paediatric neurology, ophthalmology, developmental support.
• Alagille syndrome — JAG1/NOTCH2-related cholestatic disorder; paucity of bile ducts, butterfly vertebrae, congenital heart disease and characteristic facies. Paediatric hepatology; assess cardiac/renal disease and fat-soluble vitamin status.
• Alström syndrome — Autosomal-recessive ALMS1 ciliopathy: childhood cone–rod dystrophy, hearing loss, obesity/insulin resistance, cardiomyopathy. Monitor cardiac, renal, endocrine and sensory complications with specialist services.
• Andersen–Tawil syndrome — KCNJ2-associated periodic paralysis, ventricular ectopy and dysmorphic features. Cardiac arrhythmia and neuromuscular assessment; avoid unsupervised electrolyte intervention.
• Angelman syndrome — Imprinting disorder involving maternal UBE3A: severe speech impairment, ataxia, seizures and distinctive frequent smiling/laughter. Genomic diagnosis, epilepsy and development support.
• Apert syndrome — FGFR2-related craniosynostosis with complex syndactyly of hands/feet. Early craniofacial and airway/neurosurgical assessment.

B

• Bardet–Biedl syndrome — Ciliopathy with retinal dystrophy, obesity, polydactyly, renal abnormalities and hypogonadism. Ophthalmology, renal and endocrine multidisciplinary surveillance.
• Beckwith–Wiedemann spectrum — Imprinting/11p15 overgrowth with macroglossia, lateralised overgrowth, neonatal hypoglycaemia and embryonal tumour susceptibility. Neonatal glucose safety and specialist tumour surveillance.
• Birt–Hogg–Dubé syndrome — FLCN-related skin fibrofolliculomas, lung cysts/pneumothorax and renal tumour predisposition. Renal surveillance and respiratory counselling.
• Bloom syndrome — RECQL3/BLM DNA-repair disorder: marked short stature, photosensitive erythema, infections and malignancy predisposition. Genetics and specialist cancer-risk assessment.

C

• Carney complex — PRKAR1A-associated lentigines, cardiac/cutaneous myxomas and endocrine overactivity. Urgent cardiology evaluation for symptomatic cardiac myxoma; endocrine surveillance.
• CHARGE syndrome — CHD7-related coloboma, choanal atresia, characteristic ear/hearing findings, growth and genital anomalies, congenital heart disease. Airway, cardiac, feeding and sensory priorities in infancy.
• Chediak–Higashi syndrome — LYST-related albinism, immunodeficiency, bleeding and risk of haemophagocytic inflammatory crisis. Emergency assessment for fever; specialist haematology/immunology.
• Cockayne syndrome — DNA-repair disorder featuring microcephaly, growth failure, photosensitivity and progressive neurodegeneration. Genetics and multisystem supportive care.
• Cornelia de Lange syndrome — Cohesin-pathway disorder: growth restriction, distinctive facial features, limb anomalies and developmental impairment. Assess feeding, reflux, hearing and congenital abnormalities.
• Costello syndrome — HRAS-associated RASopathy with severe feeding difficulty, cardiac hypertrophy/arrhythmia, coarse facial features and tumour risk. Cardiac and specialist tumour surveillance.
• Cri-du-chat syndrome — 5p deletion with neonatal high-pitched cry, microcephaly and developmental impairment. Genetic diagnosis and multidisciplinary developmental care.
• Crouzon syndrome — FGFR-related craniosynostosis, proptosis and midface hypoplasia, usually without hand/foot syndactyly. Protect vision and airway; craniofacial review.

D

• Dandy–Walker malformation spectrum — Posterior-fossa malformation with vermian hypoplasia and variable hydrocephalus; not itself a single genetic syndrome. Neuroimaging and neurosurgical review when signs of raised ICP.
• Diamond–Blackfan anaemia — Congenital ribosomopathy, usually severe macrocytic anaemia in infancy with reticulocytopenia and variable congenital anomalies. Haematology diagnosis, transfusion/long-term risk planning.
• Dravet syndrome — Developmental and epileptic encephalopathy often associated with SCN1A; prolonged fever-sensitive seizures beginning in infancy. Urgent status epilepticus protocols; epilepsy specialist advice on anti-seizure medication choice.
• Dubin–Johnson syndrome — Usually benign inherited conjugated hyperbilirubinaemia due to ABCC2 transporter dysfunction. Exclude hepatocellular and obstructive cholestasis first.

E

• Ellis–van Creveld syndrome — Short-rib skeletal ciliopathy with short limbs, polydactyly, ectodermal changes and frequent cardiac defects. Paediatric cardiac and orthopaedic review.

F

• Fanconi anaemia — DNA-repair/bone-marrow-failure syndrome, with congenital anomalies, pancytopenia and cancer predisposition. Haematology referral; avoid confusing with renal Fanconi syndrome.
• Floating–Harbor syndrome — SRCAP-related short stature, delayed bone age, characteristic facies and expressive language delay. Genetics and developmental assessment.

G

• Gorlin syndrome — PTCH1/SUFU-related basal-cell carcinoma and odontogenic keratocyst predisposition; some subtypes predispose to medulloblastoma. Dermatology, dental/maxillofacial and genetics surveillance; reduce UV exposure.
• Griscelli syndrome type 2 — RAB27A-related silvery hair, immunodeficiency and haemophagocytic lymphohistiocytosis risk. Severe infection/cytopenias require urgent specialist care.

H

• Hermansky–Pudlak syndrome — Oculocutaneous albinism with platelet storage-pool bleeding disorder; some subtypes cause pulmonary fibrosis. Haemostasis review before procedures, specialist lung surveillance.
• Holt–Oram syndrome — TBX5-related radial-ray upper-limb anomalies with atrial/ventricular septal defects or conduction disease. ECG, echocardiography and familial cardiac evaluation.
• Hunter syndrome (MPS II) — X-linked iduronate-2-sulfatase deficiency; coarse features, organomegaly, airway disease and skeletal changes; usually no corneal clouding. Metabolic referral; consider available disease-modifying therapy.
• Hurler syndrome (MPS I severe) — Alpha-L-iduronidase deficiency with early developmental regression, corneal clouding, organomegaly and skeletal disease. Urgent metabolic evaluation; time-sensitive specialist treatment options.

K

• Kabuki syndrome — KMT2D/KDM6A-related characteristic facies, developmental delay, short stature and immune or cardiac problems. Immunology, audiology, developmental and cardiac review.
• Kallmann syndrome — Congenital GnRH deficiency with anosmia/hyposmia and absent/incomplete puberty. Endocrine evaluation; fertility can be treatable with specialist hormone therapy.
• Klippel–Feil syndrome — Congenital cervical vertebral fusion causing short neck/reduced range; variable renal, hearing or cardiac anomalies. Assess for associated anomalies and neurological red flags before manipulation.
• Klippel–Trénaunay syndrome — Capillary malformation, venous/lymphatic malformations and limb overgrowth; risk of thrombosis and bleeding. Vascular anomalies service; distinguish from Parkes Weber syndrome.

L

• Lesch–Nyhan syndrome — X-linked HPRT1 deficiency: hyperuricaemia, severe movement disorder and self-injurious behaviour. Metabolic/neurology and behavioural support.
• Li–Fraumeni syndrome — Germline TP53 cancer predisposition: sarcoma, breast, brain and adrenocortical tumours across life. Urgent clinical genetics and structured cancer surveillance; avoid unnecessary radiation.
• Lowe syndrome — OCRL-related congenital cataracts, hypotonia/developmental impairment and proximal renal tubular dysfunction. Nephrology, ophthalmology and metabolic support.

M

• MELAS syndrome — Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes not respecting arterial territories; variable maternal inheritance. Urgent neurology and metabolic specialist discussion; do not assume thrombolysis pathway covers all episodes.
• Menkes disease — ATP7A-related copper transport disorder with sparse kinky hair, hypotonia, seizures and neurodegeneration in infancy. Time-critical metabolic/genetic referral.
• Miller–Dieker syndrome — 17p13.3 deletion associated with classic lissencephaly, severe developmental impairment and epilepsy. Paediatric neurology and genetics.
• Mowat–Wilson syndrome — ZEB2-related intellectual disability with distinctive facies, Hirschsprung disease, epilepsy or cardiac anomalies. Developmental/genetics referral and surgical/neurological support.

N

• Netherton syndrome — SPINK5-related severe ichthyosis, hair-shaft trichorrhexis invaginata and atopy; risk of fluid/heat loss in babies. Dermatology, allergy and infant skin-barrier care.
• Niemann–Pick type C — Lysosomal lipid trafficking disorder; vertical supranuclear gaze palsy, ataxia, dystonia, cognitive decline and hepatosplenomegaly. Metabolic testing, specialist management and family counselling.

O

• Ochoa syndrome (urofacial) — Abnormal crying facial expression and severe functional urinary outflow dysfunction despite no mechanical obstruction. Early urology/nephrology to protect kidneys.

P

• Pallister–Killian syndrome — Mosaic tetrasomy 12p with hypotonia, distinctive facial features, pigmentary skin changes and developmental delay. Tissue mosaicism may complicate genetic testing.
• Peutz–Jeghers syndrome — STK11-related mucocutaneous pigmentation, hamartomatous gastrointestinal polyps and cancer predisposition. Gastrointestinal bleeding/intussusception care and specialist cancer surveillance.
• Phelan–McDermid syndrome — 22q13 deletion or SHANK3-related hypotonia, severe speech delay and autistic traits. Genetics and multidisciplinary developmental support.
• Pitt–Hopkins syndrome — TCF4-related severe developmental delay, distinctive facies and episodic hyperventilation/breath-holding. Neurology, respiratory and development input.
• Pompe disease — GAA-related glycogen storage disease; infantile cardiomyopathy or later proximal/respiratory muscle weakness. Urgent metabolic/neuromuscular referral; disease-modifying therapy exists.
• Prader–Willi syndrome — Paternal 15q11–q13 expression loss: infant hypotonia/poor feeding followed by hyperphagia, endocrine and behavioural issues. Multidisciplinary growth, nutrition and endocrine management.
• Proteus syndrome — Mosaic AKT1-related asymmetric progressive tissue overgrowth and connective-tissue abnormalities, with thromboembolic risk. Specialist vascular anomalies and genetics care.

R

• Rett syndrome — MECP2-related neurodevelopmental regression after initial development, stereotypic hand movements, gait loss and breathing irregularities. Paediatric neurology; manage epilepsy, scoliosis and nutrition.
• Rubinstein–Taybi syndrome — CREBBP/EP300-related broad thumbs/great toes, developmental impairment and distinctive facial features. Assessment of cardiac, ocular and feeding complications.
• Russell–Silver syndrome — Imprinting-related intrauterine growth restriction with relative macrocephaly, asymmetry, feeding difficulty and hypoglycaemia risk. Specialist growth/feeding and endocrine management.

S

• Schwartz–Jampel syndrome — HSPG2-related persistent myotonia with skeletal dysplasia and joint contractures. Neuromuscular and anaesthetic planning.
• Smith–Lemli–Opitz syndrome — DHCR7-related cholesterol synthesis disorder with developmental impairment, microcephaly, syndactyly and genital anomalies. Metabolic and developmental review.
• Smith–Magenis syndrome — 17p11.2 deletion or RAI1 variant with sleep inversion, behavioural issues, developmental delay and characteristic features. Structured sleep and neurodevelopmental support.
• Sotos syndrome — NSD1-related childhood overgrowth, macrocephaly, advanced bone age and learning difficulties. Assess associated cardiac/renal anomalies and developmental needs.
• Sturge–Weber syndrome — Somatic GNAQ mosaicism with facial port-wine birthmark, leptomeningeal vascular malformation, epilepsy and glaucoma risk. Ophthalmology and neurology; not every facial capillary malformation implies brain disease.

T

• Tay–Sachs disease — HEXA-related GM2 gangliosidosis causing progressive neurodegeneration, developmental regression and exaggerated startle. Metabolic specialist referral; carrier counselling.
• Tuberous sclerosis complex — TSC1/TSC2-related hamartomas affecting brain, kidney, heart, skin and retina; epilepsy and renal angiomyolipoma risks. Multisystem surveillance, epilepsy and renal specialist care.

U

• Usher syndrome — Inherited retinitis pigmentosa with congenital or progressive sensorineural hearing loss, sometimes vestibular dysfunction. Audiology, ophthalmology and genetic counselling.

V

• VACTERL association — Co-occurrence of vertebral, anal, cardiac, tracheo-oesophageal, renal and limb anomalies; not a single-gene syndrome. Systematic neonatal evaluation and multidisciplinary surgery.
• Von Hippel–Lindau disease — Autosomal-dominant VHL tumour predisposition: retinal/CNS haemangioblastomas, renal clear-cell carcinoma and phaeochromocytoma. Clinical genetics and defined tumour surveillance.

W

• Waardenburg syndrome — Pigmentary changes and congenital hearing loss, sometimes Hirschsprung disease (type IV). Hearing assessment and genetics; subtypes vary.
• Williams–Beuren syndrome — 7q11.23 deletion with characteristic social/cognitive profile, supravalvular aortic stenosis and hypercalcaemia risk. Cardiology, calcium/renal and developmental surveillance.
• Wiskott–Aldrich syndrome — X-linked WAS-related immunodeficiency, eczema and thrombocytopenia with small platelets. Urgent paediatric immunology/haematology; avoid unnecessary bleeding risk.
• Wolfram syndrome — WFS1-related diabetes mellitus, optic atrophy and often hearing loss/diabetes insipidus. Endocrinology, ophthalmology and audiology follow-up.

X

• Xeroderma pigmentosum — Nucleotide-excision repair disorder with extreme UV sensitivity, early skin cancers and possible neurological disease. Strict UV protection and dermatology/genetics surveillance.

Z

• Zellweger spectrum disorder — Peroxisomal biogenesis disorders with hypotonia, liver dysfunction, hearing/vision abnormalities and severe developmental issues. Metabolic testing and multisystem paediatric support.

Clinical reasoning: Consider syndrome patterns, but avoid anchoring bias. When molecular confirmation changes screening, treatment or family counselling, clinical genetics input is valuable.

Related Makindo topics

• Down syndrome
• Kawasaki disease
• Cushing syndrome
• Wernicke–Korsakoff syndrome
• Turner syndrome 🧬
• Klinefelter syndrome 🧬
• Marfan syndrome 🧬
• Neurofibromatosis type 1 (NF1) 🧬
• Fragile X syndrome 🧬
• Noonan syndrome 🧬
• 22q11.2 deletion syndrome 🧬
• Ehlers–Danlos syndromes 🧬

UK sources / further reading: NHS England genomic testing eligibility