Table 3. [Inherited Disorders that Exhibit Diffuse Parenchymal Lung Disease as a Clinical Feature]. - GeneReviews®

Gene(s)	Disorder	MOI	Pulmonary Phenotype	Other Clinical & Laboratory Features
CFTR	Cystic fibrosis	AR	Progressive obstructive lung disease, bronchiectasis, recurrent pulmonary infections, PF, respiratory failure	Pancreatic insufficiency, malnutrition, recurrent sinusitis & bronchitis, male infertility, meconium ileus
COPA	Autoimmune interstitial lung, joint, & kidney disease (OMIM 616414)	AD	Affects children & young adults; lymphocytic lung infiltrates	High-titer autoantibodies, inflammatory arthritis, kidney disease
GBA1 (GBA)	Gaucher disease type 1	AR	<5% w/interstitial lung involvement characterized by infiltration of Gaucher cells	Childhood presentation of hepatosplenomegaly, pancytopenia, & bone disease
NF1	Neurofibromatosis 1	AD	± adult-onset parenchymal lung disease (bullae ± interstitial fibrosis) often in assoc w/pulmonary hypertension	Multiple café au lait macules, axillary & inguinal freckling, cutaneous neurofibromas, Lisch nodules, plexiform neurofibromas, ID
NKX2-1	Brain-lung-thyroid syndrome (See NKX2-1-Related Disorders.)	AD	Infant respiratory distress is common w/recurrent pulmonary infections, chronic ILD, respiratory failure	Choreoathetosis & congenital hypothyroidism
RNF168	RIDDLE syndrome (OMIM 611943)	AR	Radiation sensitivity, PF	Immunodeficiency, ID, dysmorphic features, short stature
SMPD1	Niemann-Pick disease type B (See Acid Sphingomyelinase Deficiency.)	AR	Most affected persons develop widespread ILD, recurrent lung infections, respiratory failure	Hepatosplenomegaly w/progressive hypersplenism & stable liver dysfunction; atherogenic lipid profile
TMEM173	STING-associated vasculopathy (OMIM 615934)	AD	Infantile or childhood-onset ILD	Autoinflammatory vasculopathy, severe ulcerative skin lesions (face, ears, nose, digits), arthritis, autoantibodies, immune complex deposition

Gene(s)

Disorder

MOI

Pulmonary Phenotype

Other Clinical & Laboratory Features

CFTR

Cystic fibrosis

Progressive obstructive lung disease, bronchiectasis, recurrent pulmonary infections, PF, respiratory failure

Pancreatic insufficiency, malnutrition, recurrent sinusitis & bronchitis, male infertility, meconium ileus

COPA

Autoimmune interstitial lung, joint, & kidney disease (OMIM 616414)

Affects children & young adults; lymphocytic lung infiltrates

High-titer autoantibodies, inflammatory arthritis, kidney disease

GBA1
(GBA)

Gaucher disease type 1

<5% w/interstitial lung involvement characterized by infiltration of Gaucher cells

Childhood presentation of hepatosplenomegaly, pancytopenia, & bone disease

NF1

Neurofibromatosis 1

± adult-onset parenchymal lung disease (bullae ± interstitial fibrosis) often in assoc w/pulmonary hypertension

Multiple café au lait macules, axillary & inguinal freckling, cutaneous neurofibromas, Lisch nodules, plexiform neurofibromas, ID

NKX2-1

Brain-lung-thyroid syndrome (See NKX2-1-Related Disorders.)

Infant respiratory distress is common w/recurrent pulmonary infections, chronic ILD, respiratory failure

Choreoathetosis & congenital hypothyroidism

RNF168

RIDDLE syndrome (OMIM 611943)

Radiation sensitivity, PF

Immunodeficiency, ID, dysmorphic features, short stature

SMPD1

Niemann-Pick disease type B (See Acid Sphingomyelinase Deficiency.)

Most affected persons develop widespread ILD, recurrent lung infections, respiratory failure

Hepatosplenomegaly w/progressive hypersplenism & stable liver dysfunction; atherogenic lipid profile

TMEM173

STING-associated vasculopathy (OMIM 615934)

Infantile or childhood-onset ILD

Autoinflammatory vasculopathy, severe ulcerative skin lesions (face, ears, nose, digits), arthritis, autoantibodies, immune complex deposition

From: Pulmonary Fibrosis Predisposition Overview

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Adam MP, Feldman J, Mirzaa GM, et al., editors.

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