TABLE III. Summary of QoL Studies and Selected Findings¹.

Genetic condition	References	Study population (N, age, recruit source)	Study Design	QoL Scale2	Selected Findings
Achondroplasia	Gollust et al. 2003a,b (USA)	189 adults from support org.	XS	QLI	Individuals with achondroplasia had globally poorer QoL than their unaffected first-degree relatives
					In multivariate regression, affected status was only modestly signif. for total QoL (P= 0.039) and physical QoL (P= 0.024), and NS for the other three QoL domains
					When controlling for demographics and affected status, greater perceived seriousness and lower self-esteem were strongly associated with poorer QoL in all domains
Charcot-Marie-Tooth disease	Padua et al. 2008a,b (Italy)	98 adults/teens (14 y+) with CMT1A, clinic patients	L(2 y)	SF-36	Globally poorer QoL compared to pop. norm
					QoL scores at baseline and 2 y follow-up were NS different
					Clinical/neurophysiological features (e.g., ability to toe-walk, nerve conduction) associated with QoL scores in some physical health domains, few correlations with psychosocial QoL
	Redmond et al. 2008 (Australia)	295 adults with CMT1A and CMT2, from support org.	XS	SF-36	Globally poorer QoL compared to pop. norm, NS differences in QoL between CMT types
					Physical symptoms (e.g., leg weakness, cramps) associated with lower QoL in some domains
	Vinci et al. 2005 (Italy)	121 adults/teens (15 y+), clinic patients	XS	SF-36	Globally poorer QoL compared to norm
					Disease duration negatively associated with physical QoL (PCS) but not psychosocial QoL (MCS)
	Teunissen et al. 2003 (The Netherlands)	43 adults/teens with CMT2, clinic patients	L (5 y)	SF-36	Signif. poorer QoL in most domains compared to pop. norm
					In the longitudinal cohort (n = 27), NS change in any QoL domains over the 5-year period, although clinical status/disability had worsened
Congenital adrenal hyperplasia	Jaaskelainen and Voutilainen 2000 (Finland)	32 adult clinic patients	XS	SF-36	Greater QoL in physical and psychosocial domains compared to population norms
Cystic fibrosis (CF)	Gee et al. 2003, 2005, Abbott et al. 2007, 2008 (UK)	223 adult clinic patients	XS	CFQoL	Lung function signif. associated with QoL in most domains
					Coping styles: higher optimism signif. associated with higher QoL, higher distraction signif. associated with lower QoL, hopefulness and avoidance NS associated with QoL
	Britto et al. 2002, 2004, Arrington-Sanders et al. 2006 (USA)	162 adults and children (5 y+), clinic patients	XS	SF-36 CHQ	Adults (n=48) had signif. poorer physical QoL compared to pop. norm, but NS differences in psychosocial QoL domains
					Among children/adolescents (n = 114), parent-rated QoL was signif. poorer in all physical domains compared to norms, but only signif. difference in psychosocial domains was for self-esteem
					Lung function NS correlated with QoL, but frequency of pulmonary exacerbations was signif. associated with poorer physical QoL
					Parent-rated QoL was signif. poorer than child/adolescent self-rated QoL in physical domains, but NS different for psychosocial domains
	Havermans et al. 2008 (Belgium)	57 adult clinic patients	XS	CFQ	Lung function signif. negatively associated with QoL in some physical health domains
					After controlling for lung function, anxiety and depression signif. associated with 6/12 psychosocial and 3/12 physical QoL domains
	Palermo et al. 2006 (USA)	46 children/adolescents (8–17 y), clinic patients	XS	CFQ	Pain signif. associated with QoL in physical health domains, NS for emotional or social domains
	Riekert et al. 2007 (USA)	76 adult clinic patients	XS	CFQ	Depression signif. associated with poorer QoL in all domains
	Szyndler et al. 2005 (Australia)	52 adolescents (12–18 y), clinic patients	XS	CFQ	Higher levels of psychopathology and lower optimism for the future signif. associated with poorer QoL in most domains
					Family functioning characteristics signif. associated with QoL in some domains
	Thomas et al. 2006 (Australia)	162 children/adolescents (2–19 y), clinic patients	XS	PedsQL CFQ	Globally poorer QoL compared to norm
					Lung function signif. negatively associated with some CFQ domains, NS with any PedsQL
Darier's and Hailey–Hailey diseases	Harris et al. 1996 (UK)	201 adults/teens (13 y+), clinic patients	XS	DLQI	QoL was most negatively affected in the symptoms/feelings domain (highest score of all the domains); however, mean DLQI scores were within “small” to “moderate” effect range, indicating that the disease did not have a major negative impact on patients' QoL
					NS correlation between clinical severity and QoL; NS difference in QoL between disease groups (DD vs. HHD), despite differences in symptoms
Ehlers–Danlos syndrome	Berglund and Nordstrom 2001, Berglund et al. 2003 (Sweden)	77 adults from support org.	XS	SIP	Globally poorer QoL compared to pop. norm
					Greater acceptance of disability and sense of coherence signif. associated with better QoL
Fabry disease	Miners et al. 2002 (UK)	38 male adult clinic patients	XS	SF-36	Globally poorer QoL compared to male pop. norm
					Compared to patients with severe hemophilia [Miners et al., 1999], Fabry patients had signif. poorer psychosocial QoL (MCS), but physical QoL (PCS) NS different
	Ries et al. 2005 (USA)	25 male children and adolescents (6–18 y), clinic patients	XS	CHQ	Among children (n = 9), parent-rated QoL was poorer than norms in all domains, but differences were statistically signif. for two domains
					Teens (n = 15, self-report) had signif. more pain (lower QoL) and better QoL in behavior, social, and emotional domains than norm
	Street et al. 2006 (USA)	202 adult female heterozygotes, from support org. and clinic	XS	SF-36	Globally poorer QoL compared to female pop. norm
Familial dysautonomia	Sands et al. 2006 (USA)	145 adults and children (4 y+), clinic patients	XS	SF-36 CHQ	Among adults (n = 74), NS differences in QoL than pop. norm
					Among children (n = 71), parent-rated QoL was signif. poorer in all physical domains and 2/4 psychosocial domains compared to norm; physical and psychosocial summary scores were also significantly poorer than children with various other chronic medical conditions
Friedrich Ataxia	Epstein et al. 2008 (USA)	130 adult clinic patients	XS	SF-36	Compared to age/sex-matched control group and to pop. norm, patients had signif. poorer QoL in all domains except RE and MCS (NS differences)
					Disease duration and clinical severity (neurological impairment) signif. associated only with PF domain; disability signif. associated with PF and GH domains
	Wilson et al. 2007 (Australia)	63 adult clinic patients	XS	SF-36	Globally poorer QoL compared to pop. norm, physical worse than psychosocial QoL
					Clinical severity (neurological impairment) signif. associated with only PF domain
					After controlling for severity and disease duration, age of onset was signif. associated with QoL in some domains, with adult-onset patients having lower QoL than patients whose disease began <18 y
					In multivariate regression, age of onset and severity were strongest predictors of PCS, whereas disease duration was the only factor signif. associated with MCS
Galactosemia	Bosch et al. 2004 (The Netherlands)	63 adults and children (1 y+), from support org.	XS	TAPQoL TACQoL TAAQoL	For all age groups, trend towards poorer QoL in most domains compared to healthy norms, but differences were statistically significant only in some domains (small sample sizes: n = 17 adults, n = 25 children/adolescents, n = 22 young children)
Gaucher disease	Damiano et al. 1998 (USA)	212 adults/teens (14 y+) on enzyme replacement therapy, clinic patients	XS	SF-36	Signif. poorer QoL in physical domains compared to norm, NS differences for psychosocial domains
					Ageing and clinical status (e.g., joint replacement, splenectomy) signif. associated with poorer QoL in some domains
Glycogen storage disease type 1	Storch et al. 2008 (USA)	29 children/adolescents (6–18 y), clinic patients	XS	PedsQL	Compared to healthy control group, patients had signif. lower QoL in physical and social domains, NS differences in emotional and school domains
					Compared to sample of children with various chronic medical conditions, NS differences in QoL
Hemophilia and coagulation disorders	Miners et al. 1999 (UK)	164 male adult clinic patients	XS	SF-36	Hemophilia patients had signif. worse QoL than pop. norm in physical domains, but NS differences in psychosocial domains
					Compared to patients with mild/moderate disease, patients with severe hemophilia had signif. poorer physical QoL, NS differences in psychosocial domains
	Tusell et al. 2002 (Spain)	70 male adults with severe hemophilia, clinic patients	XS	SF-36	Signif. poorer QoL than pop. norm in all domains except mental health and emotional role-functioning
	Walsh et al. 2008 (Canada)	47 male adults with mild hemophilia A from same kindred, identified through population survey	XS	SF-36	Compared to control cohort of unaffected age-matched male relatives, affected males had significantly poorer QoL in GH and RE domains, trend towards poorer QoL in all other domains
					In multivariate regression analysis, clinical status/symptoms (heart disease and joint damage) were signif. predictors of PCS, but affected status was NS (suggests that the difference in physical QoL between hemophilia and control is largely explained by heart disease and joint damage, rather than hemophilia itself)
	Solovieva 2001, Solovieva et al. 2004 (Finland)	164 adults with hemophilia, von Willebrand disease, and Factor XIII deficiency, clinic patients	L(3 y)	SF-36	Signif. poorer physical QoL and greater mental QoL than healthy control group
					NS change in QoL in most domains between baseline and 3-year follow-up
					In multivariate regression analysis, patients with severe disease and/or whose disease severity increased were more likely to have reduction in QoL over time
Hereditary hemorrhagic telangiectasia	Geisthoff et al. 2007 (Germany)	77 adults/teens (13 y+), clinic patients	XS	SF-36	Signif. poorer QoL in all domains except pain compared to pop. norm
					Clinical symptoms (e.g., epistaxis) signif. correlated with some QoL domains
					Greater perceived consequences (strain on profession, private life, and psyche) and worries about HHT signif. associated with lower QoL in all domains (P < 0.05)
	Pasculli et al. 2004 (Italy)	50 adult clinic patients	XS	SF-36	Poorer QoL in all domains except pain than pop. norm
					Clinical symptoms (e.g., epistaxis) signif. associated with PCS but not MCS
Huntington disease	Helder et al. 2001, 2002 (The Netherlands)	77 adults recruited from clinic and support org.	XS	SF-36 SIP	As assessed by the SIP: QoL was globally poorer than pop. norm Psychosocial aspects impacted to a greater extent than physical aspects Cognitive/motor functioning and disease duration predicted a signif. amount of variance in physical SIP but not psychosocial SIP
					As assessed by the SF-36, QoL was signif. poorer in most physical health domains, but NS differences for psychosocial domains; After controlling for demographics and illness-related variables, coping and illness perceptions predicted signif. amount of variance in QoL
					Coping: “acceptance” positively associated with mental health QoL domain; venting of emotions, behavioral and mental disengagement were negatively associated with QoL
					Illness identity and “cure” perceptions associated with some QoL domains
Hyperimmunoglobulinemia type D	van der Hilst et al. 2008 (International)	28 adult clinic patients	XS	SF-36	Poorer QoL in some domains than pop. norm Symptoms (frequency of attacks) signif. associated with physical QoL, NS psychosocial QoL
Marfan syndrome	Peters et al. 2002 (USA)	174 adults recruited from clinic and support org.	XS	QLI	Individuals with Marfan syndrome had signif. poorer QoL in psychological/spiritual domain than patients with cardiovascular disease, NS difference in physical health/functioning domain
Muscular dystrophies	Ahlstrom et al. 1994, Ahlstrom and Gunnarsson 1996, Ahlstrom and Sjoden Ahlstrom and Sjoden, 1996a, Natterlund et al. 2000, Bostrom et al. 2005 (Sweden)	57 adults with various MD types, identified through general population survey	L (10 y)	SIP	Globally poorer QoL compared to pop. norm, greater impact (worst QoL) in physical dimension
					NS difference in QoL between types of MD, despite differences in physical disability
					Disability signif. negatively associated with physical QoL and, to a lesser extent, psychosocial QoL
					Coping strategies signif. associated with psychosocial and overall QoL, NS for physical QoL
					Psychosocial well-being NS correlated with QoL
					QoL signif. deteriorated over the 10-year period, physical QoL to a greater extent than psychosocial QoL
					Disability signif. increased over time, whereas NS change in psychosocial well-being
	Piccininni et al. 2004 (Italy)	45 adults with various MD types, clinic patients	XS	SIP	Globally poor QoL (SIP scores in “clinically-significant impairment” range), QoL in physical dimension worse than psychosocial dimension
					Disability signif. negatively associated with QoL
					Higher psychological well-being signif. associated with better QoL
					Anxiety and depression signif. negatively correlated with QoL
	Grootenhuis et al. 2007 (The Netherlands)	107 adults and children (8 y+) with various MD types, clinic patients	XS	TAAQoL TACQoL	Children (n = 18) and adolescents (n = 22) with MD had signif. poorer QoL on some domains, but signif. better QoL in the physical functioning domains compared to healthy norms for the same age group
					Adults with MD (n = 67) had signif. poorer QoL on 8/12 domains compared to healthy norms
					Clinical severity signif. negatively associated with fine motor functioning and social functioning domains of QoL among adults
	Antonini et al. 2006 (Italy)	20 adults with myotonic dystrophy, clinic patients	XS	SF-36	Globally poorer QoL compared to healthy matched controls and pop. norm
					Clinical severity signif. associated with poorer QoL in physical domains, NS for psychosocial QoL
					Anxiety and depressive symptoms signif. associated with poorer QoL in RP and MH domains
	Ford et al. 2006 (New Zealand)	36 adults with various MD types, clinic patients	XS	SF-36	QoL signif. poorer in physical health domains as compared to pop. norm, NS for psychosocial QoL
					NS differences between patients with myotonic dystrophy versus other MD types
Neurofibromatosis type 1	Graf et al. 2006 (Switzerland)	46 children and adolescents (7–16 y), clinic patients	XS	TACQoL	Self-reported and proxy-reported QoL were signif. poorer than norm in the majority of domains
					Clinical severity and visibility signif. associated with poorer QoL in emotional domains
					Family functioning: greater cohesion and lower conflict signif. associated with better QoL when rated by parents, NS relationships with child self-reported QoL
					Family history: parents with NF1 rated their children's emotional QoL lower than did parents without NF1; family history was NS associated with children's self-reported QoL
	Kodra et al. 2009 (Italy)	129 adults clinic patients	XS	SF-36 Skindex	Significantly poorer QoL in all SF-36 domains than pop. norm
					Impact of NF1 on QoL was greater for psychosocial aspects than physical health aspects
					Visibility signif. associated with poorer skin-specific QoL (Skindex) on all domains, but NS associated with SF-36 scores
	Krab et al. 2009 (The Netherlands)	58 children and adolescents (7–17 y), clinic patients	XS	CHQ	Parent-rated QoL was signif. poorer than pop. norm in 6/8 domains
					Adolescents (n = 43 self-report) had signif. better QoL in behavior domain than norm
					Severity signif. associated with some QoL domains; visibility NS associated with QoL
	Oostenbrink et al. 2007 (The Netherlands)	34 young children (1–6 y), clinic patients	XS	ITQoL	Signif. poorer QoL in some domains compared to healthy reference sample
					Visibility signif. negatively associated with health perceptions domain of QoL
	Page et al. 2006 (USA)	166 adults recruited from clinic and support organization	XS	SF-36 SkinDex	Signif. poorer QoL in all SF-36 domains than population norms;
					Impact of NF1 on QoL was greater for psychosocial aspects than physical health aspects
					Visibility signif. associated with poorer skin-specific QoL (Skindex) on all domains, but NS associated with SF-36 scores
					Clinical severity signif. associated with poorer QoL in all SF-36 domains and 2/3 Skindex domains (functioning and physical symptoms, NS emotional symptoms)
	Wolkenstein et al. 2001 (France)	128 adult clinic patients	XS	SF-36 SkinDex	Signif. poorer QoL in all SF-36 domains than population norms
					Impact of NF1 on QoL was greater for psychosocial aspects than physical health aspects
					Visibility signif. associated with poorer QoL on all Skindex domains and most SF-36 domains
					Clinical severity signif. associated with poorer QoL in some SF-36 domains, but NS associated with Skindex scores
	Wolkenstein et al. 2009 (France)	79 children and adolescents (8–16 y), clinic patients	XS	DISABKIDS CDLQI	Using DISABKIDS, impact on total QoL was greater (i.e., worse QoL) for NF1 than for asthma
					Using the CDLQI, impact on QoL was lower for NF1 (i.e., better QoL) than for other skin diseases (psoriasis, eczema, acne)
					Disease complications/symptoms signif. associated with greater impact (lower QoL)
Osteogenesis imperfecta	Widmann et al. 2002 (USA)	30 adult clinic patients	XS	SF-36	QoL signif. poorer in most physical health domains than norm, NS differences in psychosocial QoL
Phenylketonuria	Landolt et al. 2002 (Switzerland)	37 children/adolescents (3–18 y) on treatment, clinic patients	XS	TACQoL	As rated by parents, children/adolescents with PKU had signif. poorer QoL than norms in one psychosocial domain (positive emotional functioning), but NS differences in any other QoL domains
	Simon et al. 2008 (Germany)	67 adult clinic patients on treatment	XS	PLC	No signif. differences in any QoL domains compared to pop. norm
Pompe disease	Hagemans et al. 2004 (International)	210 adults from support org.	L (1 y)	SF-36	Disability signif. associated with lower QoL in PF, SF, and RE domains
					Longer disease duration signif. associated with lower PF scores, but higher RP and MH scores
					Mean QoL scores for the Dutch subgroup (n = 51) were signif. lower than population norms for 3/4 physical health and 2/4 mental health domains; NS differences for BP, RE, and MH
					In the Dutch cohort who were followed longitudinally (n = 38), no signif. change in QoL over the 1 y follow-up period, even among those who reported physical deterioration
Porphyria	Holme et al. 2006 (UK)	220 adults and children (5 y+) with erythropoietic protoporphyria, clinic patients	XS	DLQI CDLQI	For both adults and children, QoL was markedly impaired (mean DLQI/CDLQI scores were within the “very large effect” range)
					Clinical severity signif. associated with QoL
	Millward et al. 2001 (UK)	81 adults with acute porphyrias, clinic patients	XS	MOS	Globally poorer QoL compared to pop. norm
					Patients manifesting symptoms had signif. lower QoL than patients without symptoms (latent)
					Patients with acute intermittent porphyria had more pain and poorer social functioning than patients with other types (variegate porphyria and hereditary coproporphyria)
Prader–Willi syndrome	Caliandro et al. 2007 (Italy)	29 adults and children (5 y+), clinic patients	XS	SF-36 CHQ	Compared to pop. norm, adults and children had signif. poorer QoL in most domains
Sickle cell disease	McClish et al. 2005 (USA)	308 adult clinic patients	XS	SF-36	Patients with sickle cell had signif. poorer QoL in all domains except mental health, as compared to population norms and patients with cystic fibrosis
					Pain signif. negatively associated with QoL in all domains except mental health
	Palermo et al. 2002 (USA)	58 children/adolescents (5–18 y), clinic patients	XS	CHQ	Globally poorer QoL than healthy controls
					Disease complications negatively
					associated with physical QoL, but NS with psychosocial QoL
	Panepinto et al. 2005 (USA)	99 children and adolescents (5–18 y), clinic patients	XS	CHQ	Parent-rated QoL was signif. poorer than norm in physical and psychosocial domains
					Adolescents (n = 53) self-rated their QoL as signif. poorer than norms in physical domains, but NS different in psychosocial domains
					QoL as rated by parents tended to be lower than adolescents' self-reported QoL
					Disease complications (number of crises) was signif. negatively correlated with physical QoL
Turner syndrome	Carel et al. 2005 (France)	568 adult females treated with growth hormone, clinic patients	XS	SF-36	NS differences in any QoL domains compared to reference sample
					Psychological distress signif. correlated with lower QoL (women with symptoms of psychological distress had signif. poorer QoL in all domains than those without symptoms)
					Height and other treatment-related variables NS associated with QoL
X-linked agammaglobulinemia	Howard et al. 2006 (USA)	41 male adult clinic patients	XS	SF-12	NS differences in QoL between patients and pop norms, except GH domain
					Lung disease signif. associated with lower MCS scores, but NS difference in PCS
	Winkelstein et al. 2008 (USA)	25 male adult clinic patients	XS	SF-12	Trend towards lower QoL among patients than pop norms, but NS

¹Abbreviations used in Table III: support org., support organization; signif., significant; NS, not significant; y, years; XS, cross-sectional; L, longitudinal; pop. norm, population norm; PCS, physical component score; MCS, mental component score; PF, physical functioning; RP, role physical; BP, bodily pain; VT, vitality; MH, mental health; GH, general health perceptions; RE, role emotional; SF, social functioning.

²See Table V QoL scale abbreviations.