FZD6

Twenty-nail dystrophy (OMIM 161050)

AR

Onychauxis, hyponychia, onycholysis

Nonsyndromic nail disorder LMX1B

Nail-patella syndrome

AD

Classic clinical tetrad of changes in nails, knees, elbows, presence of iliac horns

Nails may be absent, hypoplastic, or dystrophic; ridged longitudinally or horizontally; pitted; discolored; separated into 2 halves by longitudinal cleft or ridge of skin; thin or (less often) thickened. USB1

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Poikiloderma with neutropenia

AR

Post-inflammatory poikiloderma chronic noncyclic neutropenia typically assoc w/recurrent sinopulmonary infections (often) bronchiectasis. risk for myelodysplastic syndrome. Other findings incl nail dystrophy palmar/plantar hyperkeratosis.

Thickened, hyperkeratotic toenails are common; dystrophic nails that can slough may also be seen.

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Gene

Disorder

MOI

Clinical Characteristics

Comment BRCA1 BRCA2 BRIP1 ERCC4 FAAP100 FANCA FANCB FANCC FANCD2 FANCE FANCF FANCG FANCI FANCL FANCM PALB2 RAD51 RAD51C REV7 RFWD3 SLX4 UBE2T

XRCC2

Fanconi anemia (FA)

ARXLAD1

The primary clinical features of FA are physical abnormalities, progressive BMF manifesting as pancytopenia, cancer susceptibility; however, some persons w/FA have neither physical abnormalities nor BMF.

The 1st clinical manifestation of both FA DC/TBD may be BMF. DNAJC21 EFL1 SBDS

SRP54

Shwachman-Diamond syndrome (SDS)

ARAD2

Exocrine pancreatic dysfunction w/malabsorption, malnutrition, growth failure; hematologic abnormalities w/single- or multi-lineage cytopenias susceptibility to MDS AML; bone abnormalities. In almost all affected children, persistent or intermittent neutropenia is a common presenting finding.

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Dermatologic

Thorough skin nail exam

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Dental

Baseline eval for oral hygiene, leukoplakia, oral squamous cell cancer

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Otolaryngologic

Baseline eval for leukoplakia squamous cell head/neck cancer

Growth

development

Clinical assessment

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Ophthalmic

Thorough exam for complications related to lacrimal duct stenosis, abnormal eyelash growth, retinal disorders incl exudative retinopathy

Gastrointestinal

hepatic

History of potential swallowing difficulties /or enteropathy; baseline liver function tests

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Genitourinary

For males, assessment for urethral stenosis

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Musculoskeletal

Consideration of baseline bone mineral density scan at age 14 yrs or at diagnosis; history of any joint problems

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Neurologic

If early-onset neurologic findings (e.g., ataxia) or many complications are found in other initial evals, consider brain MRI to evaluate for cerebellar hypoplasia or intracranial calcifications.

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Hematologic

Eval by hematologist incl CBC bone marrow aspiration biopsy to determine if signs of BMF are present

Consideration of HLA typing of affected person, unaffected sibs, parents in anticipation of possible need for HCT Pulmonary

Cardiologic

Baseline eval for cardiac malformations

Genetic

counseling

By genetics professionals1

To obtain a pedigree inform affected persons their families re nature, MOI, implications of DC/TBD to facilitate medical personal decision making Family support resources