Approach to

Question 1

Cutis aplasia

• Definition
• Histology

Answer 1

DEFINITION:
- Rare congenital malformation characterized by a local defect of the epidermis, dermis, and subcutaneous tissue occurring predominantly over the vertex (crown) of the scalp. Hair does not grow over the affected area(s), and the underlying bone growth is can be abnormal.

• There may be a single area with a ‘raw’ appearance - the skin is a thin transparent membrane - or several small defects.

HISTOLOGY
- Cutis aplasia lesions histologically show variable absence of epidermis, dermis, subcutaneous tissue, muscle, or bone.

Question 2

Cutis aplasia

• Management and prognosis
• Investigations (non-genetic)
• Recurrence risk

Answer 2

MANAGEMENT:

• Conservative
• Defect may change into a raised area of scarred granulation tissue

INVESTIGATIONS:

• Consider skull X-ray if the defect is very large to check for parietal foramina - occasionally, there are bony defects of the skull underlying cutis aplasia, so consider a CT head.
• Head ultrasound in infants.

RECURRENCE RISK:

• Depends of the specific diagnosis (underlying cause)
• Isolated cutis aplasia congenita can follow AD inheritance - NB: It’s possible that apparent isolated cutis aplasia could be a part of the Adams-Oliver spectrum, so consider arranging for detailed scans of the digits and heart in pregnancy.

Question 3

Cutis aplasia

• Key points on history

Answer 3

KEY POINTS ON HISTORY:
A. Three generation family history: 
- scalp defects; 
- cardiac abnormalities; 
- limb defects; neonatal deaths

B. Prenatal history:

• drug exposure (methimazole, carbimazole, misoprostol)
• infection (intrauterine varicella or herpes)

C. Delivery:
- difficult instrumental delivery leading to traumatic scalp defect

D. HPI:

• visual difficulties (cone-rod dysfunction, myopia)
• deafness (Johanson-Blizzard syndrome)
• pyloric atresia (EB with pyloric atresia aka Carmi syndrome)
• developmental delay (chromosomal abnormalities)

Question 4

Cutis aplasia

• Key points on physical exam

Answer 4

KEY POINTS ON PHYSICAL EXAM

• position and number of skin defects (clues: bitemporal in Setleis syndrome and focal facial dermal dysplasia; random distribution in Goltz syndrome)
• hair growth (clues: unruly hair with cowlicks in Johanson-Blizzard syndrome; poor hair growth over the temples in Pallister-Killian syndrome)
• facies (clues: check eyes for structural malformations and epibulbar dermoids; beaked nose and hypoplastic alae nasi in Johanson-Blizzard syndrome)
• chest (cardiac murmurs may be a clue for Adams-Oliver syndrome or Johanson-Blizzard syndrome)
• genitals (hypospadias)
• evidence of transverse limb deficiency (clue: Adams-Oliver syndrome, check all fingernails and toenails)
• skin abnormalities at other sites (clues: deficiency, blisters, scarring, pigmentary abnormality)

Question 5

Cutis aplasia

• Differential diagnosis

Answer 5

DDx:
- Isolated defect (familial - cutis aplasia congenita)

• Non-genetic causes:
  Birth trauma (e.g., scalp electrode avulsion)
  Amniotic bands
  Intrauterine vascular disruption (e.g., secondary to embolism from co-twin loss)
  Teratogen exposure, e.g. infections and drugs (misoprostol, cocaine, methotrexate, angiotensin-converting enzyme inhibitors, methimazole, carbimazole, other antithyroid drugs*, benzodiazepines, valproic acid)
• Chromosomal disorders
  Trisomy 13
  Wolf-Hirschhorn syndrome (4p- syndrome)
  Variety of rare unbalanced chromosomal rearrangements
• Genetic syndromes
  Adams-Oliver syndrome
  Johanson-Blizzard syndrome
  Scalp-ear-nipple (SEN) syndrome (Finlay-Marks syndrome)
  Setleis syndrome
  Microphthalmia with linear skin defects syndrome (MLS)
  Goltz syndrome
  Delleman syndrome (Oculocerebrocutaneous syndrome)
  Carmi syndrome (Congenital pyloric atresia with epidermolysis bullosa known)
  Kabuki syndrome
  Limb body wall complex
  Knobloch syndrome
  Various ectodermal dysplasias

NB: If the scalp defect is in the parietal area, it may be associated with parietal foramina: type of congenital calvarial defect that results from delayed/incomplete ossification of the parietal bone; patients may also have cranium bifidum, headache, seizures, and cleft lip or palate; AD condition caused by heterozygous mutation in the MSX2 gene or BMS1 gene.

NB: MSX2 mutation/deletion is not a frequent cause of scalp defects.