Clinical features of early onset progeroid syndromes
| RD | Classical HGPS | Atypical HGPS6 | MAD type A (OMIM 248370) | MAD type B (OMIM 608612) | Patient FT | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| *Two cases of lethal neonatal MAD have been reported.21,22 | ||||||||||||
| †At least one additional mutation, in the same or a second gene, is likely to be required. | ||||||||||||
| m, months; HGPS, Hutchinson-Gilford progeria syndrome; MAD, mandibuloacral dysplasia; NR, not reported; RD, restrictive dermopathy; y, years. | ||||||||||||
| Inheritance | AD | AD, sporadic | AR | AR | AR | AR | ||||||
| LMNA mutation | IVS11+1G→A c.1824C→T (G608G) | G608G G608S | K542N | R527H | NR | – | ||||||
| ZMPSTE24 mutation | c.1085_1086insT† | NR | NR | NR | c.1085_1086insT W340R | c.1085_1086insT N265S | ||||||
| Presentation | 3rd trimester/congenital | 6 m–2 y | 18 m–2 y | 4 y* | 2 y* | 10 weeks | ||||||
| Average life span | Weeks | 13 y | 10–16 y | 3rd decade or later | 3rd decade or later | 2.75years | ||||||
| Growth retardation | Intrauterine | 6 m–1 y | + | 4–5 y | 2 y | Infancy | ||||||
| Joint contractures | Intrauterine | From infancy | From childhood | From childhood | From childhood | Neonatal | ||||||
| Skin abnormalities | Intrauterine, generalised taut, thin skin | From infancy, sclerodermoid changes, atrophic changes | Atrophic, sclerodermoid changes, mottled pigmentation | Atrophic, hyperpigmentation | Atrophic, hyperpigmentation | Neonatal, sclerodermoid, indurated over trunk+lower limbs, oedema | ||||||
| Lipodystrophy | – | Generalised | Generalised | Partial (extremities) | Generalised | Lower limbs | ||||||
| Alopecia | + | From childhood | From childhood | From childhood | From childhood | – | ||||||
| Osteolysis | – | From infancy | + | Childhood | Childhood | Present at 10 weeks | ||||||
| Insulin resistance | – | + | – | + | + | – | ||||||
| Dyslipidaemia | – | + | – | + | + | Mild | ||||||
| Atherosclerosis | – | + | NR | NR | NR | Possible transient ischaemic attack | ||||||
| Facial features | Pinched nose, small “O” shaped mouth, micrognathia | Prominent veins, “glyphic” nose, micrognathia, sparse eyebrows | Pinched nose, sparse eyebrows and lashes, prominent eyes, micrognathia | Beaked nose, micrognathia, pinched face | Beaked nose, micrognathia, pinched face | Prominent scalp veins, “glyphic nose”, micrognathia | ||||||
| Skeletal features | Large fontanelle, thin, dysplastic clavicles, reduced bone density, overtubulated long bones | Delayed closure of cranial sutures, wormian bones, osteolysis of distal phalanges and clavicles, osteoporosis, pyriform thorax, coxa valga | Delayed closure of cranial sutures, clavicular hypoplasia, acro-osteolysis | Delayed closure of cranial sutures, clavicular hypoplasia, osteolysis of distal phalanges, mandible and clavicles | Delayed closure of cranial sutures, clavicular hypoplasia, osteolysis of distal phalanges, mandible and clavicles, Calcified nodules on digits | Thin skull, wormian bones, osteolysis of distal phalanges and clavicles, fractures, lytic areas in tibia, humerus+cervical spine | ||||||
| Other | Polyhydramnios, premature rupture of membranes, pulmonary hypoplasia | Horse-riding stance, absent sexual maturation, delayed dentition | Absent/impaired sexual maturation, crowded teeth | Premature loss of dentition | Premature loss of dentition, delayed sexual maturation Focal segmental glomerulosclerosis, collapsing variant | |||||||