16.3 Genetics, Dysmorphology & Newborn Screening Follow-Up

Genetics is clinical category #20 — lower volume on the outline, high cost if you miss it. The CPNP-PC is not a biochemical-genetics fellowship. You must act on newborn screening, deliver syndrome-specific primary care for the diagnoses you will actually see, take a three-generation history, and refer when the pattern is more than one isolated finding.

Quick Answer: Newborn screening is a screen, not a diagnosis. An abnormal result means urgent confirmatory testing and, for galactosemia, CAH, and congenital hypothyroidism, same-week (often same-day) clinical action. Down syndrome primary care: echocardiogram, hearing, TSH (newborn, 6 months, 12 months, annually), atlantoaxial awareness. Turner: short, webbed neck, delayed puberty → karyotype. Draw a three-generation pedigree. Do not list every NBS disorder.

Newborn screening is not a diagnosis

State newborn screening (NBS) is a public-health screen designed to catch treatable diseases before they are clinically obvious. A positive or borderline result is not the disease. False positives occur; false negatives occur; an out-of-range result still demands prompt confirmatory testing coordinated with the state program and the relevant specialist. Do not tell a family “the state already diagnosed PKU” from a screening punch, and do not wait for the 2-month well visit because “it is probably a false positive.”

You do not need to recite every analyte on every state panel. You do need a reflex for the disorders whose delay causes immediate catastrophe — the ones PNCB-style stems actually use.

If the family has not been reached, you close the loop. Document contact, feeding change, and the confirmatory appointment. An abnormal NBS is a time-critical inbox, not a curiosity.

Down syndrome: AAP health supervision in primary care

Trisomy 21 is the syndrome you will manage longitudinally. Confirm the karyotype (or know it was confirmed). Deliver the diagnosis with the infant present, accurate language, and connection to Down syndrome-specific resources. Then execute AAP 2022 Health Supervision for Children and Adolescents With Down Syndrome — you are not improvising a list from memory of “what Down syndrome kids get.”

Echocardiogram in the newborn period even if there is no murmur. Congenital heart disease (AVSD, VSD, tetralogy, and others) is present in roughly 40–50%. A quiet precordium does not clear the heart. Refer cardiology for defects or pulmonary hypertension.

Hearing. Conductive loss from chronic effusion is common; sensorineural loss occurs too. Follow AAP timing: newborn diagnostic hearing care as indicated, then behavioral audiology on the recommended cadence (commonly every 6 months until ear-specific normal hearing is established, often after age 4, then at least annually). Do not skip audiology because the infant “startles to a clap.”

Thyroid. If the state NBS measured only T4, obtain a TSH. Repeat TSH at 6 months, 12 months, and annually (every 6 months if antithyroid antibodies are present). Hypothyroidism is common and treatable; it will masquerade as slowing development if you stop checking after the nursery.

Atlantoaxial instability. Symptomatic instability is uncommon, but missed myelopathy is devastating. Teach families the warning signs (change in gait, neck pain, torticollis, weakness, hyperreflexia, bowel/bladder change). Perform a neurologic exam at health supervision visits. Routine cervical radiographs in asymptomatic infants are not indicated (AAP 2022). Discuss cervical-spine precautions for anesthesia, surgery, and positioning. Imaging belongs to symptoms, special procedures, or specific sports-clearance contexts — not a yearly souvenir x-ray in a well 6-month-old.

Also built into primary care: ophthalmology in infancy and on the AAP cadence, OSA vigilance (very common), feeding/aspiration, celiac screening when indicated, and developmental supports. You do not need to dump the entire 2022 table into an item answer; you need echo, hearing, TSH, atlantoaxial awareness as the reflex cluster.

Turner, Fragile X, Marfan

Turner syndrome (45,X or mosaic) presents as a short girl with delayed puberty or amenorrhea, often with webbed neck, lymphedema, shield chest, wide-spaced nipples, left-sided cardiac lesions (coarctation, bicuspid aortic valve), and horseshoe kidney. Karyotype is the diagnostic test. Do not call her “constitutional delay” for years while mid-parental height is average and breast development never starts. Screen heart and kidneys once the diagnosis is in play, and refer genetics and endocrinology (estrogen replacement timing is not a primary-care solo project). Remember the Section 16.2 trap running the other direction: hypothyroid skin and bowel findings still get T4/TSH first; Turner and Hashimoto can coexist, but you do not skip the thyroid because you thought of a karyotype.

Fragile X syndrome is the most common inherited cause of intellectual disability (Down syndrome is more common overall but usually de novo). Features: long face, large ears, macroorchidism after puberty, hypotonia, connective-tissue laxity, autism-spectrum and hyperarousal behaviors. Inheritance is FMR1 CGG-repeat expansion. Test when unexplained intellectual disability or autism has suggestive features or a maternal family history of ID, premature ovarian insufficiency, or adult tremor/ataxia (premutation). Refer genetics for counseling — this is a family diagnosis, not only a child diagnosis.

Marfan syndrome and related connective-tissue disorders: tall habitus, arm-span excess, pectus, scoliosis, arachnodactyly, lens dislocation, and — the must-not-miss — aortic-root dilation. Do not clear that adolescent for basketball until echocardiography and genetics/cardiology have spoken. Homocystinuria can mimic the habitus and is a different disease (thrombosis risk, different lens direction in classic teaching). Your job is suspicion plus referral, not Ghent-criteria virtuosity on a multiple-choice island.

Three-generation family history

A genetics history that lists only “mom’s allergies” is not a pedigree. Record three generations: siblings, parents, aunts/uncles, grandparents; pregnancy losses; sudden death; intellectual disability; early cancer; consanguinity; similarly affected relatives; and the ancestry that changes carrier risk. Draw it when the problem is syndromic, developmental, or recurrent. Update it — families remember new diagnoses between visits.

When to refer genetics

Refer when the child has two or more major anomalies, one major anomaly plus dysmorphic features, unexplained developmental delay or autism with dysmorphology, a recognizable syndrome you cannot fully manage alone, ambiguous genitalia, FTT plus congenital anomalies, a positive family history that implies Mendelian risk, consanguinity with unexplained disease, or an abnormal NBS or chromosomal test that needs counseling. Isolated, well-explained, familial variants (familial macrocephaly with typical development and large-headed parents) do not need an automatic genetics appointment.

Primary care can order a karyotype for suspected Turner or Down syndrome mosaicism in the right context; chromosomal microarray is a first-tier test for unexplained developmental delay/ID/autism in many genetics pathways — often after hearing, lead, and a look at the child, and often with genetics so that a variant of uncertain significance does not become a discarded inbox result. Do not shotgun microarray on every slow-gaining infant with dilute formula.

Exam traps

• Treating NBS as a final diagnosis — or as noise to repeat at the next well visit.
• Continuing breast milk in a galactosemia-positive screen until “genetics calls back.”
• Skipping the echo in Down syndrome because there is no murmur.
• Annual cervical spine films in an asymptomatic infant as if AAP required them.
• Forgetting TSH surveillance in Down syndrome after a normal nursery screen.
• Calling Turner constitutional delay without a karyotype.
• Sports clearance in a Marfan-habitus teen without an aortic-root look.
• Trying to memorize every NBS disorder instead of the action rule: screen → confirm urgently → treat the time-critical few → refer the rest.

Close the NBS loop the day it lands, supervise Down syndrome with echo/hearing/TSH/spine awareness, karyotype the Turner pattern, and refer genetics when the child is more than one isolated finding.